
==== Front
Sports Med Health Sci
Sports Med Health Sci
Sports Medicine and Health Science
2666-3376
Chengdu Sport University

S2666-3376(24)00025-8
10.1016/j.smhs.2024.02.004
Review
Exercise and nutrition benefit skeletal muscle: From influence factor and intervention strategy to molecular mechanism
Feng Lili fenglili@zju.edu.cn
a⁎
Li Bowen a
Yong Su Sean a
Wu Xiaonan b
Tian Zhenjun tianzhj@snnu.edu.cn
c⁎⁎
a College of Education, Physical Education Department, Zhejiang University, Hangzhou, 310058, China
b The Information and Communication College, National University of Defense Technology, Xi'an, 710106, China
c Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi'an, 710119, China
⁎ Corresponding author. College of Education, Physical Education Department, Zhejiang University, Hangzhou, 310058, China fenglili@zju.edu.cn
⁎⁎ Corresponding author. Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, Xi'an, 710119, China tianzhj@snnu.edu.cn
27 2 2024
12 2024
27 2 2024
6 4 302314
5 12 2023
24 1 2024
18 2 2024
© 2024 Chengdu Sport University. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.
2024
Chengdu Sport University
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sarcopenia is a progressive systemic skeletal muscle disease induced by various physiological and pathological factors, including aging, malnutrition, denervation, and cardiovascular diseases, manifesting as the decline of skeletal muscle mass and function. Both exercise and nutrition produce beneficial effects on skeletal muscle growth and are viewed as feasible strategies to prevent sarcopenia. Mechanisms involve regulating blood flow, oxidative stress, inflammation, apoptosis, protein synthesis and degradation, and satellite cell activation through exerkines and gut microbiomes. In this review, we summarized and discussed the latest progress and future development of the above mechanisms for providing a theoretical basis and ideas for the prevention and treatment of sarcopenia.

Keywords

Skeletal muscle
Sarcopenia
Exercise
Diet
Exerkines
Signaling pathway
Satellite cells
==== Body
pmcAbbreviations

ADP adenosine diphosphate

AIF apoptosis-inducing factor

Akt protein kinase B

ALCAT1 lysocardiolipin acyltransferase 1

ALS autophagy-lysosomal system

AMP adenosine monophosphate

AR androgen receptor

ATP adenosine triphosphate

Bax Bcl-2-associated X protein

BCAAs branched-chain amino acids

BMI body mass index

CKD chronic kidney disease

COPD obstructive pulmonary disease

CSA cross-sectional area

CVD cardiovascular disease

Endo G endonuclease G

ER endoplasmic reticulum

ERK extracellular regulated protein kinases

ERRα estrogen-related receptor-α

ES muscle electrical stimulation

FNDC5 fibronectin type III domain containing 5

GDF15 growth differentiation factor 15

GSH-Px glutathione peroxidase

HF heart failure

HR heart rate

HIIT high-intensity interval training

HFD high-fat diet

IGF-1 insulin-like growth factor-1

IL interleukin

iNOS inducible nitric oxide (NO) synthase

JAK Janus kinase

LCBE lonicera caerulea berry extract

LBP lipopolysaccharide-binding protein

MAPK mitogen-activated protein kinase

Mets metabolic syndrome

MI myocardial infarction

mTOR mammalian target of rapamycin

NADPH nicotinamide adenine dinucleotide phosphate

NAFLD non-alcoholic fatty liver disease

NO nitric oxide

NRF nuclear respiratory factors

PGC-1α peroxisome proliferator-activated receptor γ coactivator-1α

PHGG partially hydrolyzed guar gum

PI3K phosphatidylinositol 3 kinase

PKC protein kinase C

PPARγ peroxisome proliferator-activated receptor γ

p70S6K 70 ​kDa ribosomal protein S6 kinase

REDOX oxidation-reduction reaction

RM repetition maximum

RNS reactive nitrogen species

ROS reactive oxygen species

SC satellite cell

SCFA short-chain fatty acids

SOCS suppressor of cytokine signaling

SOD superoxide dismutase

STAT signal transducer and activator of transcription

TFAM transcription factor A

TGF-β transforming growth factor-β

TNF-α tumor necrosis factor-α

TNFRI tumor necrosis factor receptor I

UCP2 uncoupling protein 2

ULK1 uncoordinated 51-like kinase 1

UPR mt mitochondrial unfolded protein response

UPS ubiquitin-proteasome system

VC vitamin C

WBV whole-body vibration

wk week

YAP Yes-associated protein

1 Introduction

Sarcopenia is a progressive and generalized skeletal muscle disease induced by various physiological and pathological factors,1,2 manifesting as a decline in skeletal muscle mass and function.3,4 Sarcopenia is commonly accompanied by profound negative effects on quality of life and is associated with clinical complications, including obesity, hypertension, diabetes, and cardiovascular diseases, which form a harmful cycle, as it could lead to frailty, fractures, disability, hospitalization, and even death.5 Therefore, it is of great significance to summarize the risk factors and preventive strategies in patients with sarcopenia. The causes of sarcopenia could be categorized into pathological and non-pathological factors. Pathological factors include osteoarthrosis, cardiovascular diseases, and metabolic diseases, whereas non-pathological factors include aging, poor diet, and physical inactivity.

2 Pathological causes

The loss of skeletal muscle mass and function was related to the activation of inflammation and biomechanical stress signaling in patients with osteoarthritis.6 Patients with osteoarthritis of the hip and knee were commonly accompanied by declines in muscle mass and strength, resulting in further injury to the joint and reduced physical activity ability and quality of life.7 Clinical data showed that patients with rheumatoid arthritis (RA) were particularly susceptible to sarcopenia, with a 30% prevalence rate.8,9 In patients with cardiovascular disease (CVD), cardiac dysfunction induces blood insufficiency and capillaries closure in skeletal muscle, thereby aggravating the ischemia and hypoxia injury of skeletal muscle cells.10 Ischemia and hypoxia injury triggered excessive oxidative stress and inflammation, leading to mitochondrial dysfunction, protein degradation, and apoptosis in skeletal muscle, finally resulting in sarcopenia.10,11 Metabolic syndrome (Mets) and non-alcoholic fatty liver disease (NAFLD) were prone to sarcopenia due to their similar pathogenesis, such as insulin resistance and chronic inflammation.12,13 Decreased insulin sensitivity induced muscle metabolic dysfunction in patients with Type 2 diabetes, further leading to loss of muscle mass.14 Mets patients were commonly accompanied by insulin resistance and metabolic dysfunction of skeletal muscle, which led to mitochondrial dysfunction, imbalance between protein synthesis and degradation, and excessive oxidative stress and inflammation (Fig. 1). In addition, cancer-induced sarcopenia, one of the major causes of death in patients, is commonly caused by medication side effects with medical therapy, malnutrition, vascular embolism, inflammation, metabolic dysfunction, protein degradation, and exceed autophagy.15 Patients with esophageal, gastric, lung and colorectal cancer, especially pancreatic cancer, were accompanied by skeletal muscle atrophy in the progress of chemotherapy, and which would lead to poor-prognosis in patients.16Fig. 1 Causes of sarcopenia can be categorized into pathologic and non-pathologic. Pathologic causes consist of osteoarthrosis, metabolic diseases, and cardiovascular diseases. Non-pathologic causes include aging, irrational diet structure, and physical inactivity. These causes induce low blood flow, excessive oxidative stress and inflammation, cell apoptosis, and protein degradation in skeletal muscle, leading to sarcopenia.

Fig. 1

3 Non-pathological causes

3.1 Aging

The prevalence of sarcopenia increased with age, manifesting as decreased muscle mass, strength, and exercise intolerance.4,17 Studies showed that the skeletal muscle metrics decreased with increasing age, including cross-sectional area (CSA) of skeletal muscle, calf circumference, calf circumference/BMI ratio, knee extension strength, and gait speed.18,19 Aging-induced alterations, such as denervation, chronic systemic inflammation, and insulin resistance, could disrupt the balance of protein synthesis and degradation, leading to mitochondrial dysfunction, eventually resulting in the loss of skeletal muscle mass and function (Fig. 1).

3.2 Irrational diet structure

There were associations between sarcopenia and nutrient absorption and utilization abilities as well as dietary patterns consisting of protein, fat, carbohydrates, and various micronutrients, especially vitamins.20,21 Low protein uptake led to the loss of muscle mass and strength.22,23 Meanwhile, a comparative study found a negative correlation between the ‘mushrooms-fruits-milk’ diet and sarcopenia.24 Unhealthy long-term living habits like smoking and drinking could induce brain-gut axis dysfunction and oral diseases, resulting in nutritional deficiencies.25 In addition, poor sleep quality disrupted the circadian rhythm and biological clock, reduced dietary intake, and ultimately inhibited muscle protein synthesis.26 Proper nutrient supplementation, including high-protein, high-quality fat, carbohydrate, and sufficient vitamins, along with regular exercise, could effectively improve muscle mass and function. As regular exercise promotes nutritional absorption and utilization, thus preventing sarcopenia (Fig. 1).

3.3 Physical inactivity

A physically inactive lifestyle, such as sedentary and bedridden, could reduce skeletal muscle function and contribute to the increased prevalence of sarcopenia. For example, hospitalized older adults were particularly susceptible to sarcopenia due to the loss of muscle mass, strength, and mobility.27 Sarcopenia involves both mass loss and function decline. Exercise, combined with a proper diet, could produce beneficial effects on the prevention and treatment of sarcopenia (Fig. 1).

4 Prevention of sarcopenia

Currently, there is a lack of specific drugs for treating sarcopenia. This study summarizes the pharmacological interventions based on clinical and animal research findings28, 29, 30, 31: vitamin D, combined estrogen-progesterone, growth hormone, growth hormone-releasing hormone, testosterone, combined testosterone-growth hormone, insulin-like growth factor-1(IGF-1), angiotensin-converting enzyme inhibitors, dehydroepiandrosterone, and pioglitazone. However, some pharmacological treatments could induce toxic damage to the heart, liver, kidney, and other organs. Therefore, the administration route, dosage, and duration of such treatment need to be considered and explored with circumspection, and it should be performed in a standardized and personalized manner. Compared with pharmacological therapy, non-drug methods such as exercise, muscle electrical stimulation, and nutritional supplements are safer, especially with the combination of exercise and nutrition. Moreover, exercise could decrease the side effects caused by the toxicity of drugs and promotes nutrient absorption and utilization, thereby helping to prevent and alleviate sarcopenia.

4.1 Aerobic exercise training

Aerobic exercise, as a traditional exercise form, is more acceptable among patients with sarcopenia due to its safety, effectiveness, and diversity of forms. Study demonstrated that aerobic exercise (50 ​min/d, 3 ​d/wk, 24 wk, 70% HRreserve) alone improved endurance and aerobic fitness. Furthermore, when combined with essential amino acids supplementation, it effectively increased muscle strength and protein synthesis in older adults.32 Combined acute aerobic training (60 ​min/d, 7d, 60%–65% HRmax) and vitamin D potentiated the metabolic benefits of exercise by reducing intramyocellular lipid and increasing V˙O2 level in muscle tissue.33 Insufficient nutrition and physical inactivity are critical causes of sarcopenia, as it accelerates the loss of skeletal muscle during aging or pathological states. Aerobic exercise could mobilize whole-body muscles, increase peripheral capillary density,34,35 improve mitochondrial function and muscle metabolism,36 and balance oxidation-reduction reaction (REDOX),37 ultimately alleviating sarcopenia. Therefore, combining such an approach with nutritional support could further promote muscle mass and function, which is of great significance in preventing sarcopenia.

4.2 Resistance exercise training

Resistance exercise has been well known for promoting muscle hypertrophy by activating myogenesis, increasing protein synthesis and inhibiting protein degradation-related molecular signaling.38,39 Resistance training (3 ​d/wk, 12 wk, 70%–80% 1 RM) increased myonuclear and the percentage of the largest muscle fibers in older adults.40 Progressive resistance exercise of upper and lower (2-3 ​d/wk, 4 month, 75% 1 RM) was effective in improving lower limb muscle strength and exercise performance in chronic obstructive pulmonary disease (COPD) patients with low muscle mass, and oral nutritional supplementation further enhanced the beneficial effects of exercise.41 High-intensity resistance exercise (2 ​d/wk, 18 month) combined with protein and calcium intake significantly improved skeletal muscle mass and exercise capacity in older patients with sarcopenia.42 Nevertheless, the effects of resistance exercise on muscle mass declined after detraining.42 Therefore, exercise should be performed on a long-term basis, and its forms should be easy to persist.

4.3 High-intensity interval training

High-intensity interval training (HIIT) improved cardiac and pulmonary function, skeletal muscle mass and function, exercise capacity, and quality of life in older patients with systemic diseases.43,44 After a 12-week HIIT (3 ​d/wk, 90% HRmax), muscle mass, strength, and exercise capacity were significantly increased in young and older people.45 HIIT (25 ​min/d, 3 ​d/wk, 8 wk, 70%–85% HRmax) improved aerobic fitness and muscle strength. Furthermore, when combined with intermittent fasting, it effectively promoted a greater gain in fat-free mass and greater loss of body fat in women with obesity.46 Moreover, HIIT was also found to promote protein synthesis, improve muscle metabolic capacity and insulin sensitivity, and reverse high-fat diet (HFD)-induced sarcopenia, at least partially via the modulation of mammalian target of rapamycin (mTOR) signaling.47 Thus, HIIT could prevent and ameliorate sarcopenia under various physiological or pathological conditions.

4.4 Whole-body vibration

Whole-body vibration (WBV) is a form of passive training initiated by applying physical stimulation using vibration devices, which is suitable for older adults and mobility-limited patients with various diseases. Low-level WBV training with 6 Hz–26 ​Hz frequency and 2 mm–4 ​mm amplitude (5-10 s/d ​× ​60 ​s/d, 3 ​d/wk, 16 wk) increased muscle mass and strength, exercise ability, and quality of life, as well as alleviated age-related sarcopenia in frail older adults.48 Two studies demonstrated that 12-week WBV intervention (40 ​Hz, 4 ​mm, 4 ​s/d × ​90 ​s/d, 3 ​d/wk; 12 ​Hz, 3 ​mm, 10 s/d ​× ​60 ​s/d, 3 ​d/wk) also improved neuromuscular innervation, enhanced exercise ability, and increased skeletal muscle mass and function of older patients with sarcopenia.49,50 Furthermore, thigh muscle CSA and strength, and exercise ability were significantly improved in older women after WBV training (20 Hz–40 ​Hz, 2 mm–4 ​mm, 3 d/wk-5 ​d/wk, 10 wk).51 Thus, the prevention and treatment of WBV in sarcopenia is attributed to its effects on improving neuromuscular function and muscle mass. Importantly, it could be used as a physiotherapy technique for older adults and post-menopausal women in the community. Therefore, it is critical to establish a precise and scientifically-based WBV training program for preventing and alleviating sarcopenia in clinical practice, particularly with the appropriate frequency and amplitude.

4.5 Muscle electrical stimulation

Muscle electrical stimulation (ES) is an individual intervention to increase muscle mass and strength by external electrical pulse stimulation of local muscles, such as pectoralis, dorsal, and limb muscles. Some studies have revealed that whole-body ES with frequency of 85 ​Hz and impulse width of 350 μs increased skeletal muscle mass and strength, improves muscle function, promotes exercise ability, alleviates sarcopenia, and reduces sarcopenia-induced clinical complications.52, 53, 54 It has been gradually used as the treatment of clinical muscle diseases, which is especially suitable for patients unable or unwilling to perform conventional exercise training regularly. Further research should clarify the molecular mechanisms and combine ES with current exercise in the rehabilitation context.

4.6 Nutritional intervention

A proper dietary pattern, especially a protein-rich and antioxidant-rich diet, is essential for maintaining muscle mass and strength. In addition, vitamins, fatty acids, and antioxidants could also benefit muscle mass. A 15-year study revealed that the traditional dietary pattern increased muscle mass, and the anti-inflammatory dietary pattern containing a wide variety of vegetables, fruits, whole grains, nuts and proteins increased skeletal muscle mass and function.55 The anti-inflammatory dietary pattern was found to be more effective than the traditional one.55 The supplementation of vitamin E and high-quality fats like omega-3 fatty acids and oleic acid significantly aggrandized muscle mass and strength and walking speed and prevented muscle loss in older adults.56 Branched-chain amino acids (BCAAs) such as leucine, valine and isoleucine promoted protein synthesis, increased muscle mass and strength, and improved muscle health in older adults.57 In order to improve the dietary pattern, it is recommended to increase the proportion of BCAAs-rich foods such as meat, fish, shellfish, legumes, and cereals. Moreover, it was reported that L-glutamine products combined with exercise training improved muscle antioxidant capacity and glycemia balance, increased muscle mass, and alleviated diabetes-induced sarcopenia.58 Thus, a rational dietary pattern combined with exercise training could reverse the sarcopenia process.

Since sarcopenia is affecting skeletal muscles in all total body, we recommend training the large muscle groups through total body approach. Evidence showed positive and significant effects of resistance training on muscle mass and strength, and physical performance.59 Furthermore, a systematic review and meta-analysis demonstrated that among intervention methods such as aerobic, resistance, resistance with aerobic, and whole-body vibration, resistance exercise is the most effective for improving muscle mass and strength.60,61 The load methods of resistance exercise can be divided into three types: body weight, resistance band and free weight, but there was no significant difference between the three methods.62 Although low-intensity resistance training (50% 1 RM) is sufficient to induce gains in muscle strength, we recommend high-intensity resistance training (80% 1 RM) to promote maximal strength gains.59 In addition, after review of evidence for multinutrient supplementation, best evidence is available to recommend leucine, which has significantly beneficial effects on muscle mass in older adults with sarcopenia.63,64 Protein supplementation on top of resistance training is recommended to increase muscle mass and strength.64,65

5 Underlying mechanisms that exercise and nutrition interventions prevent sarcopenia

5.1 Exercise and nutrition increased the muscular perfusion

Aging and physical inactivity could lead to an insufficient supply of blood and nutrients to skeletal muscle, followed by a decline in skeletal muscle mass and function. Evidence has demonstrated that combining exercise with L-citrulline increased endothelial nitric oxide (NO) synthesis, improved vascular and mitochondrial function, increased blood perfusion and nutrition exchange, promoted oxygen utilization and protein synthesis, inhibited apoptosis in skeletal muscle, and ultimately contributed to reversing the process of sarcopenia.66 In both compensatory cardiac hypertrophy rats and heart failure (HF) patients, HIIT, mechanical stretch, and voluntary wheel running were found to enhance muscle angiogenesis and perfusion as well as improving skeletal muscle performance and exercise endurance.67,68 Exercise alone (resistance exercise and HIIT) or in combination with whey protein promoted muscle capillarization and metabolite exchange, thereby increasing protein synthesis and oxidative metabolism.69 In addition, studies have shown that exercise increased muscle capillarization, shortened the distance between capillaries and satellite cells, and optimized the spatial distribution, which was conducive to satellite cell activation and proliferation and inhibiting aging-induced sarcopenia.70, 71, 72 In summary, the combination of exercise and nutrition could improve muscle capillarization, vascular function, and antioxidant enzyme activation, promote nutrient exchange between blood and tissues, and further enhance muscle metabolism and protein synthesis, thereby improving muscle mass and function. Importantly, exercise could activate satellite cells to promote the remodeling and regeneration of skeletal muscle fibers.70, 71, 72 Therefore, combining exercise with nutrition supplements is an effective strategy to maintain and improve skeletal muscle mass and function under aging and pathologic conditions.

5.2 Exercise and nutrition promoted exerkines secretion to protect skeletal muscle

Exerkines are cytokines, mRNAs, or gut microbiomes that are released in response to exercise from many different organs and tissues (including liver, skeletal muscle, heart, kidney, brain, and fat) and exert their effects via autocrine, paracrine, or endocrine pathway.73,74 Notably, levels of exerkines are closely related to exercise intensity and amount.

5.2.1 Exerkines acted on muscle themselves or mediated organizational cross-talk

In humans and mice, the growth differentiation factor 15 (GDF15) expression in serum and muscle increased with age, whereas exercise reducing GDF15 level and improved aging muscle mass and function and.75 It was preliminary showed that the potential use of GDF-15 as a biomarker for sarcopenia in animal models and humans. IGF-1 is a key factor in skeletal muscle growth and hypertrophy. Aerobic and resistance exercise alleviated myocardial infarction (MI)-induced loss of muscle mass by inhibiting protein degradation and apoptosis as well as promoting myogenesis via IGF-1/IGF-1R-phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway.76 A study revealed that aerobic exercise could alleviate the levels of oxidative stress and apoptosis in skeletal muscle following MI, partly via up-regulating fibronectin type III domain containing 5 (FNDC5/Irisin) and inhibiting lysocardiolipin acyltransferase 1 (ALCAT1) expression.77 In addition, resistance exercise combined with Leucine supplement increased IGF-1 and FNDC5/Irisin levels in muscle and serum, which promoted muscle protein synthesis.78 Aged mice-related study revealed that γ-Oryzanol diet improved muscle antioxidant and anti-inflammation capacities by activating peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) and estrogen-related receptor-α (ERRα) signaling, and inhibiting transforming growth factor-β (TGF-β)/Smad signaling, which was conducive to skeletal muscle function and exercise ability.79

5.2.2 Exosomes mediated exercise-induced protection

Sarcopenia is a frequent complication of chronic kidney disease (CKD), but exercise could reverse such a process. Exosomes play a pivotal role in mediating exercise-related beneficial effects. A study revealed that resistance exercise increased miR-23a and miR-27a expressions in mice with CKD, and miR-23a/miR-27a activated Akt signaling, inhibited myostatin and downstream Smad-2/3 signaling, decreased protein degradation, reduced muscle loss, improved grip strength, and resulted in alleviated CKD-induced sarcopenia.80 Exercise also improved PPARγ expression, reduced miR-29b level, activated Akt/mTOR pathway, inhibited protein degradation and apoptosis, increased muscle weight and CSA, and ultimately ameliorated muscle atrophy following angiotensin Ⅱ-induced HF.81 Moreover, the importance of miRNAs in mediating the effects of exercise has been shown. A study demonstrated that muscle miRNAs expressions were sensitive to carbohydrate intake during the initial phase of recovery after aerobic exercise. After aerobic exercise, carbohydrate intake increased Let7i-5p and miR-195-5p levels, reduced activities of ubiquitin-mediated proteolysis, autophagy-lysosome system, myostatin, and caspase3 signaling, inhibited protein degradation, and ultimately facilitated muscle recovery.82

5.2.3 Gut microbiome was closely linked with muscle health

Gut microbiota composition and diversity might be the determinants of skeletal muscle metabolism and function.83 Partially hydrolyzed guar gum (PHGG) contained-fiber-rich diet alleviated muscle wasting by fermenting dietary polysaccharides into short-chain fatty acids (SCFA), restoring the gut barrier function, reducing systemic inflammation lipopolysaccharide-binding protein (LBP) and interleukin (IL)-6 in serum, suppressing ubiquitin-proteasome system (UPS) and autophagy pathways, and resulting in inhibition of muscle protein degradation in cancer mice.84

Skeletal muscle is the main site of protein storage and metabolism, serving as an important source of cytokines, which is determined by exercise training and nutritional intake. Thus, exercise combined with nutrition could stimulate cytokine secretion in muscle or other organs (fat, liver, heart, and brain), activate downstream signaling pathways, improve muscle anti-inflammatory and antioxidant capacities, and promote muscle protein synthesis. At the same time, exercise combined with nutrients alleviate oxidative stress, inflammation, and protein degradation, as well as prevent or reverse the loss of skeletal muscle via inhibiting negative mechanisms of inflammatory mediator and protein degradation.

5.3 Exercise promoted mitochondrial homeostasis

Mitochondria play a crucial role in regulating the metabolic status of skeletal muscle, which demonstrate remarkable plasticity, adjusting its volume, structure, and function in response to chronic exercise, aging, and disease.85 Mitochondrial biogenesis requires the coordination of multiple cellular events, including mtDNA replication, transcription from mitochondrial promoters, processing and stabilization of mitochondrial RNAs, translation, assembly of respiratory chain complexes and electron transport chain.86 Exercise activates a large number of signaling pathways that converge to initiate mitochondrial biogenesis.85 PGC-1α plays an important role in regulating mitochondrial biogenesis and activates multiple transcription factors, including nuclear respiratory factors (NRF) 1 and 2, mitochondrial transcription factor A (TFAM), and uncoupling protein 2 (UCP2).87,88 PGC-1α cooperated with NRFs and promoted the expression of TFAM to regulate mitochondrial biogenesis.89 During exercise, adenosine triphosphate (ATP) is continuously synthesized and broken down into adenosine diphosphate (ADP) and adenosine monophosphate (AMP).90 Binding of AMP to the γ subunit of the heterotrimeric AMP-activated protein kinase (AMPK) causes AMPK conformational changes and enhances its phosphorylation.91 AMPK activation leads to the phosphorylation of PGC-1α, further stimulating mitochondrial biogenesis.92 Exercise promote mitophagy and remove dysfunctional mitochondria in skeletal muscle thought activating the AMPK and its representative downstream signaling molecules, such as PGC-1α and uncoordinated 51-like kinase 1 (ULK1).93 The activation of AMPK signaling pathway promoted PGC-1α/NRFs/TAFM complex and regulated mitochondrial biogenesis in response to exercise.87 Mitophagy is important in removing damaged or dysfunctional mitochondria and maintaining mitochondria homeostasis,94 which can be enhanced by exercise through activating AMPK signaling in skeletal muscle.95 The previous studies showed that running exercise promoted mitochondrial biogenesis and triggered the antioxidant defence system in muscle,96 and skeletal muscle demonstrated a greater mitophagy drive post-exercise.95 The mitochondrial unfolded protein response (UPR mt) is known as a conservative mechanism in response to mitochondrial dysfunction.97 Mitophagy and UPR mt, two mitochondrial quality control mechanisms, are central to maintaining mitochondrial homeostasis in skeletal muscle and can be triggered by exercise.87,98,99 Therefore, exercise represents a viable, nonpharmaceutical therapy with the potential to reverse and enhance the impaired mitochondrial function (Fig. 2).Fig. 2 Exercise-mediated mitochondrial homeostasis. Exercise activates AMPK and downstream signaling molecules such as PGC-1α and ULK1, further promotes mitochondrial biogenesis and mitophagy, partially via through NRF and TFAM signaling, results in mitochondrial homeostasis. AMP: adenosine monophosphate; AMPK: adenosine monophosphate-activated protein kinase; ATP: adenosine triphosphate; NRF: nuclear respiratory factor; PGC-1α: peroxisome proliferator activated receptor γ coactivator (PPARγ)-1α; TFAM: mitochondrial transcription factor A; ULK1: uncoordinated 51-like kinase 1.

Fig. 2

5.4 Exercise and nutrition inhibited excessive oxidative stress

A study showed that both aerobic and resistance exercise increased activation of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduced reactive oxygen species (ROS) level and cell oxidative damage, inhibited UPS activation, activated satellite cells, promoted muscle fibers repair and regeneration, and ultimately alleviated HF-induced skeletal muscle atrophy.100 It has also been reported that aerobic exercise improved mitochondrial function, reduced oxidative stress and protein ubiquitin degradation, and inhibited apoptosis via activating AMPK/PGC-1α and Akt/mTOR signaling pathways in skeletal muscle of aged mice.101 Exercise converted ROS into more stable molecules (oxygen and water molecules), scavenged free radicals, regulated the production of ROS and RNS, and resulted in maintaining oxidation-reduction homeostasis; importantly, apart from exercise intervention, nutritional supplements, including vitamin E/α-tocopherol, Vitamin C (VC)/L-ascorbic acid, carotenoids, and polyphenols, were effective strategies to alleviate oxidative stress, and increase muscle mass and strength.102 Nutraceuticals combined with exercise reduced ROS accumulation and inflammatory cytokines, improved muscle antioxidant and anti-inflammatory capacities, alleviated oxidative stress and inflammation, and inhibited skeletal muscle atrophy induced by cancer.103 Therefore, combining exercise with nutrition is beneficial to improving skeletal muscle mass and function and preventing sarcopenia by regulating oxidative stress, inflammation, and apoptosis within the physiological range (Table 1 and Fig. 3).Table 1 Regulation of signaling pathways and biological effects under exercise and nutrition to inhibit sarcopenia.

Table 1Signaling Pathways	Molecular and Biological effects	References	
AMPK-PGC-1α	ROS↓ MDA↓ SOD↑ CAT↑ GSH-Px↑ NRF1↑ NRF2↑ TFAM↑Bax↓	improved mitochondrial function and quality control	79,101,104	
Bcl2↑ Cyt C↓ Caspase9↓	inhibited oxidative stress and cell apoptosis	
Caspase3↓		
NRF2-AREs	CAT↑ SOD1↑ SOD2↑ TUNEL positive particles↑	improved antioxidant capacity	105	
Pax7↑ MyoD↑	reduced cell apoptosis	
	promoted SC proliferation and differentiation	
HSP27 signaling	AIF↓ Endo G↓	inhibited AIF and Endo G translocation	106	
to reduce cell apoptosis	
PKC-Nox2/Nox4	ROS↓	alleviated oxidative stress	104	
iNOS-NO	TNF-α↓ MCP1↓ NF-κB↓ NQO1↑ HO-1↑	increased anti-inflammatory and antioxidant capacity	79,104	
decreased inflammation and oxidative stress levels	
PI3K-Akt	Bax↓ Bcl2↑ Cyt C↓ Caspase3↓Atrogin-1↓ MuRF1↓ MAFbx↓ myostatin↓ mTOR↑ p70S6K↑	down-regulated UPS signaling	76,77,101,102,104,107, 108, 109, 110, 111, 112	
4-EBP1↑ Pax7↑	reduced protein ubiquitination degradation	
	promoted synthesis	
	reduced cell apoptosis and increased cell proliferation	
	improved SC self-renewal and regenerative potential	
TGF-β-smad	Nox4↓ MuRF1↓	inhibited oxidative stress and protein degradation	79,102,108	
Pax7↑ MyoD↑	increased SC number and activation	
Wnt/β-catenin	Pax7↑ Myf5↑ MyoD↑	promoted SC proliferation and differentiation	113	
Hippo/YAP	Pax7↑ MyoD↑	increased SC activation and myogenesis	114	
JAK2-STAT3-SOCS	Pax7↑ PCNA↑ MyoD↑	increased SC proliferation and differentiation	115	
Myogenin↑	promoted myogenesis	
AIF: apoptosis-inducing factor; AREs: antioxidant-responsive DNA elements; Akt: protein kinase B; AMPK: adenosine monophosphate-activated protein kinase; Bax: Bcl2-associated X; Bcl-2: B-cell lymphoma-2; CAT: catalase; Cyt C: Cytochrome C; Endo G: endonuclease G; GSH: glutathione; GSH-Px: glutathione peroxidase; HO-1: heme oxygenase-1; HSP27: heat shock protein 27; iNOS: inducible NO synthase; JAK: Janus kinase; MAFbx: muscle atrophy F-box; MCP-1: monocyte chemoattractant protein-1; MDA: malondialdehyde; mTOR: mammalian target of rapamycin; MuRF1: muscle ring finger 1; Myf5: myogenic factor 5; MyoD: myogenic differentiation; NF-κB: nuclear factor-κB; NO: nitric oxide; Nox: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; NQO1: NADPH quinone oxidoreductase 1; NRF: nuclear respiratory factor; PCNA: proliferating cell nuclear antigen; PGC-1α: peroxisome proliferator activated receptor γ coactivator (PPARγ)-1α; p70S6K: 70 ​kDa ribosomal protein S6 kinase; PI3K: phosphatidylinositol 3 kinase; PKC protein kinase C; ROS: reactive oxygen species; SC: satellite cell; SOCS: suppressor of cytokine signaling; SOD: superoxide dismutase; STAT: transducer and activator of transcription; TFAM: mitochondrial transcription factor A; TGF-β: transforming growth factor-β; TNF-α: tumor necrosis factor-α; YAP: Yes-associated protein; 4-EBP1: 4E binding protein 1.

Fig. 3 Promoting anti-inflammation and antioxidant capacity of skeletal muscle by exercise and nutrition supplements. Exercise stimulates cytokine secretion and further activates PI3K-Akt and AMPK-PGC-1α pathways, to alleviate oxidative stress and inflammation by regulating NF-κB, NRF and TFAM and reducing ROS production and accumulation. Meanwhile, exercise and nutrition interventions increase glucose uptake and inhibit PKC-Nox2/Nox4 pathway to reduce ROS levels. Akt: protein kinase B; AMPK: adenosine monophosphate-activated protein kinase; GPCRs: G protein-coupled receptors; mTOR: mammalian target of rapamycin; Nox: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; NRF: nuclear respiratory factor; PI3K: phosphatidylinositol 3 kinase; PKC protein kinase C; ROS: reactive oxygen species; TFAM: mitochondrial transcription factor A.

Fig. 3

5.5 Exercise and nutrition alleviated inflammation

Inflammation is a complex physiological response to stimulation, and there is an interaction between inflammation and oxidative stress. Chronic systemic inflammation induced muscle mitochondrial dysfunction, excessive oxidative stress and apoptosis, resulting in metabolic disorders and muscle loss. Exercise training has been shown to have important anti-inflammatory effects by upregulating anti-inflammatory cytokines through interlinked molecular mechanisms in skeletal muscle.116 IL-6 is the main cytokine present in circulation during exercise, which produced by skeletal muscle depending on the mode, frequency, duration, and intensity of exercise.116,117 IL-6 has long been regarded as a pro-inflammatory factor, but recent findings suggest that it also has anti-inflammatory effects,118,119 manifested by inhibitory effects on pro-inflammatory cytokines (such as tumor necrosis factor-α (TNF-α) and IL-1).116 IL-10 and IL-1Ra are well-known anti-inflammatory cytokines,120 which is also associated with exercise.116,121 IL-10 can inhibit the production of inflammatory cytokines IL-1α, IL-1β and TNF-α to exhibit anti-inflammatory effects.122 IL-1Ra is an anti-inflammatory cytokine of the IL-1 family, which blocked the action of IL-1α and IL-1β by competitively ligand-specific binding to the IL-1R with higher affinity.123,124 The appearance of circulating IL-10 and IL-1Ra following exercise contributes to mediating the anti-inflammatory effect of exercise. IL-13 is an anti-inflammatory cytokine that regulates microglia/macrophage polarization toward an anti-inflammatory phenotype and stimulates the production of IL-10,125,126 which is also closely linked to exercise. Studies showed that exercise could increase IL-13 level in circulation,127 adipose tissue128 and muscle.129

5.6 Exercise and nutrition reduced cell apoptosis

Aging and diseases induced excessive accumulation of ROS, increased inflammatory cytokine levels, triggered oxidative stress and inflammation, and resulted in cell apoptosis in muscle, whereas exercise reduced oxidative stress and inflammation, inhibited apoptosis and protein degradation, and alleviated muscle atrophy,130 partially via Akt and AMPK pathways.131 Aging-related chronic systemic inflammation increased TNF-α in circulation, which was bound with tumor necrosis factor receptor I (TNFRI) to induce apoptosis, whereas exercise reduced TNF-α, TNFRI, and pro-apoptotic proteins Caspase8 and Caspase9 levels, inhibited apoptosis, maintained skeletal muscle mass.132 Caspase12, an endoplasmic reticulum (ER) stress-specific indicator, activated Caspase9 and Caspase3, further inducing apoptosis. A study showed that six weeks of swimming reduced Caspase12 expression in the skeletal muscle of diabetic mice.133 Therefore, exercise is viewed as an effective strategy to inhibit oxidative stress, inflammation, and cell apoptosis in skeletal muscle as well as to ameliorate sarcopenia.

However, excessive oxidative stress and inflammation are induced by fatigue after exercise. Therefore, it is important to relieve exercise fatigue to enhance exercise protective effects. A study found that lonicera caerulea berry extract (LCBE) and VC reduced apoptosis-related proteins Bax, cytochrome C (Cyt C), Caspase9, and Caspase3 levels via inducible nitric oxide (NO) synthase (iNOS)/NO and protein kinase C(PKC)-nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2(Nox2)/Nox4 pathways in muscle following exercise fatigue; meanwhile, mitochondrial biosynthesis, antioxidant capacity, and exercise endurance were improved by long-term exercise and LCBE through activating AMPK-PGC-1α-NRF-1-TFAM pathway; and LCBE promoted cells proliferation by up-regulating miR-NA-133a/IGF-1/PI3K/Akt/mTOR signaling, which ultimately improved skeletal muscle mass and exercise capacity in mice.104 Apoptosis-inducing factor (AIF) and endonuclease G (Endo G) are caspase-independent mediators that induced apoptosis to accelerate aging-induced muscle atrophy, whereas running exercise combined with caloric restriction decreased the translocation of AIF and Endo G from the cytoplasm to the nucleus and down-regulated pro-apoptotic signaling.106

In summary, the mechanisms by which exercise inhibited apoptosis to prevent muscle atrophy might be involved in the following: (1) exercise decreased oxidative stress and inflammation, and further inhibited the activation of caspase8 and caspase3; (2) exercise improved mitochondrial function, reduced AIF and Endo G levels, inhibited pro-apoptotic Bax and Cyt C release, and blocked Cyt C binding to caspase 9 to form apoptosome; (3) exercise inhibited ER-mediated caspase12 activation, further blocking the activation of caspase3 (Table 1 and Fig. 4).Fig. 4 Modulation of cell apoptosis pathways in skeletal muscle by exercise and nutrition intervention. TNF-α binds to TNFRI, further activates caspase8 and caspase 3, to induce apoptosis. And apoptosis executive signal-caspase3 also is activated by ER stress-specific indicator caspase 12, and Bax Cyt C is released by mitochondria. Moreover, mitochondria release AIF and Endo G to active caspase-independent apoptosis signaling. Which could be reversed by exercise and nutrition interventions. AIF: apoptosis-inducing factor; Bax: Bcl2-associated X; Bcl-2: B-cell lymphoma-2; Cyt C: Cytochrome C; Endo G: endonuclease G; FADD: Fas-associating protein with a novel death domain; TNF-α: tumor necrosis factor-α

Fig. 4

5.7 Exercise and nutrition regulated protein synthesis and degradation

Skeletal muscle mass is determined by the balance between protein synthesis and degradation. Physical inactivity and insufficient nutrition decrease muscle protein synthesis and induce muscle mass and function decline. A study has demonstrated that resistance exercise improved the rate of protein synthesis, inhibited protein degradation, and increased aging muscle CSA and strength.134 Aerobic combined with resistance exercise promoted protein synthesis, reduced muscle protein degradation by regulating inflammation, autophagy mediators, and UPS activation, and ultimately alleviated muscle atrophy in aged obese patients.135 Moreover, resistance exercise combined with milk and vitamin D promoted protein synthesis, and increased muscle mass and strength, which were beneficial to preventing aging-induced muscle atrophy.136 Dietary intake of protein after resistance exercise activated mTORC1 and downstream target 70 ​kDa ribosomal protein S6 kinase (p70S6K), improved protein synthesis, and increased aging muscle mass.137

Codium fragile is rich in lysophosphatidyl choline, α-tocopherol, and unsaturated fatty acids, which are important to maintain and promote skeletal muscle health.107 PGC-1α and mTORC1 are key regulators of muscle protein synthesis, energy metabolism, and muscle mass and function via regulating UPS and autophagy-lysosomal system (ALS).107,138 The animal experiment revealed that muscle mass and exercise endurance were increased in mice fed with Codium fragile, and the beneficial effects of Codium fragile on muscle were performed by activating PGC-1α-related signaling and Akt/mTORC1 pathway, promoting mitochondrial biogenesis and protein synthesis, and increasing muscle fibers CSA.107 It was demonstrated that lifelong aerobic exercise also improved mitochondrial function, promoted protein synthesis, and resulted in inhibiting aging-induced muscle atrophy via AMPK/PGC-1α and Akt/mTOR pathways.101 An imbalance of protein synthesis and degradation directly causes skeletal muscle atrophy, while inhibiting excessive activation of UPS and ALS is beneficial to protein synthesis and degradation balance. Exercise and nutrition interventions improve mitochondrial function, promote protein synthesis, and reduce UPS and ALS activation through Akt-mTORC1 and PGC-1α pathways in skeletal muscle (Table 1).

5.8 Exercise and nutrition activated satellite cells

Satellite cells (SCs) are stem cells located between the basal membrane and membrane of muscle fibers. They are activated by exercise and mechanical stimulations, leading to their proliferation and differentiation, which promotes muscle fiber repair and regeneration.139, 140, 141 Exercise activated SC proliferation and differentiation, increased muscle capillary density in aged type II muscle fibers, improved muscle mass and strength, and resulted in preventing aging-induced sarcopenia.142 The combinations of resistance and aerobic exercise increased SC number and pool, muscle capillarization and CSA, and inhibited muscle atrophy following bariatric surgery.143 Endurance exercise training promoted muscle SC self-renewal and proliferation, reduced mitochondrial respiration, and inhibited inflammation and fibrosis in damaged muscle fibers.144 Other studies have found that voluntary wheel running alleviated skeletal muscle atrophy by activating SC proliferation and differentiation and promoting myogenesis, partially via Wnt/β-catenin and Hippo/Yes-associated protein (YAP) pathways in skeletal muscle.113,114 Importantly, exercise also inhibited muscle growth-inhibitory pathways and activated SCs to promote skeletal muscle hypertrophy. High-expression TGF-β impeded SC activation and protein synthesis, and weakened muscle hypertrophy via Smad signaling, whereas resistance exercise reversed the negative effects caused by TGF-β activation.108 A transcriptome study found that the PI3K/Akt pathway played a key role in resistance exercise-induced SCs self-renewal and proliferation.110 Apart from exercise, nutrients should be considered as a feasible intervention. Sulforaphane, a natural compound derived from cruciferous vegetables, activated SC proliferation and differentiation and reversed aging-related loss of muscle mass and function via NRF2 signaling.105 A study has found that lemon myrtle extract activated SC proliferation and promoted muscle protein synthesis through interleukin-6 (IL-6).145 It has also been reported that in IL-6-treated C2C12 ​cells and primary human myoblasts, high concentrations of IL-6 activated SCs and promoted cell proliferation and differentiation via activating Janus kinase (JAK)-signal transducer and activator of transcription (STAT)-suppressor of cytokine signaling (SOCS) pathway.115 Thus, lemon myrtle could be considered as a novel nutritional intervention for preventing sarcopenia. Resistance exercise activated SC proliferation and differentiation, and promoted muscle hypertrophy through IL-6/STAT inflammatory signaling. Therefore, IL-6 and its downstream played an important role in the effects of exercise or nutrients on activating muscle SCs proliferation and differentiation. In androgen receptor (AR)-treated C2C12 ​cells, stretch (mimic appropriate exercise) promoted cell proliferation through the AR-IGF-1/IGF-1R-p38 and extracellular regulated protein kinases (ERK)1/2 pathways.111 Thus, it makes sense to explore whether exercise can activate the proliferation and differentiation of satellite cells to promote muscle fibers regeneration and hypertrophy through the AR-IGF-1/IGF-1R-mitogen-activated protein kinase (MAPK) pathway. Combining exercise with nutrient ingestion is an effective and feasible strategy for promoting SC activation and myogenic differentiation.

Activation of SCs was beneficial to muscle fibers regeneration, while excessive activation led to SC exhaustion. Thus, when SCs participated in muscle fiber repair and regeneration, treadmill training prevented excessive activation of SCs and maintained its regenerative potential by up-regulating IGF binding protein 7 (IGFBP7), blocking the binding of IGF receptor (IGFR) to its ligands, further inhibiting PI3K/Akt/mTOR pathway.109 In conclusion, activation of SCs requires mechanical stimulation and cytokines, and capillary, as the transport channels of oxygen, nutrient and cytokines, are also critical factors in regulating the state and function of SCs. Exercise activates SC proliferation and differentiation to improve muscle fiber regeneration by promoting capillarization in skeletal muscle and up-regulating SC activation-related signaling; meanwhile, it inhibits SC excessive activation and damage by blocking activation-related signaling pathways (Table 1 and Fig. 5).Fig. 5 Activation of satellite cells proliferation and differentiation to muscle fibers regeneration. The complex mechanisms were activated by exercise and nutrients, as shown in the picture. Satellite cell activation-related Pax7, Myf5 and MyoD were up-regulated via the above pathways to promote the proliferation and differentiation of satellite cells. Importantly, exercise could up-regulate IGFBP7 to inhibit IGF/PI3K/Akt/mTOR for preventing excessive activation of satellite cells, which was benefitial to maintaining satellite cell survival and regenerative potential. Akt: protein kinase B; AR: androgen receptor; IGF-1: insulin-like factor-1; IGF-1R: IGF-1 receptor; IL-6: interleukin-6; JAK: Janus kinase; MAPK: mitogen-activated protein kinase; mTOR: mammalian target of rapamycin; Myf5: myogenic factor 5; MyoD: myogenic differentiation.

Fig. 5

6 Conclusion and perspective

Sarcopenia is a progressive and degenerative skeletal muscle disease, and its prevention and treatment are major areas of scientific research. Advances in research on its definition, adverse outcomes, diagnosis, causes, and interventions are important to prevent and treat sarcopenia. Compelling evidence has confirmed that aging, insufficient nutrition, physical inactivity, and diseases contribute to sarcopenia. In addition, some lifestyle habits, such as smoking and excess alcohol consumption, are also conducive to sarcopenia. Therefore, it is of great significance to maintain a rational diet and regular exercise. Furthermore, sufficient accumulation of muscle mass and strength in mid-life is beneficial in preventing age-related muscle atrophy. Maintaining regular physical activity and an optimized diet during young adulthood or middle age are effective strategies to prevent sarcopenia. Exercise and nutrition interventions regulate complex pathological or physiological mechanisms, including oxidative stress, inflammation, apoptosis, cytokines release, protein synthesis, and activation of SCs (Fig. 6), which are critical for sarcopenia prevention and treatment. Most importantly, lifelong exercise and a reasonably good diet also have practical significance.Fig. 6 Protective effects of exercise and nutrition interventions in sarcopenia. The current concerning types of exercise in improving skeletal muscle mass and function are resistance exercise, aerobic exercise, high-intensity interval training, whole-body vibration, and muscle electrical stimulation. Exercise and nutrition supplements stimulate cytokines secretion and activate mechanisms and downstream to increase muscle blood flow, ameliorate oxidative stress and inflammation, reduce cell apoptosis, promote protein synthesis, and activate satellite cells, result in preventing muscle atrophy and improving hypertrophy. Akt: protein kinase B; AMPK: adenosine monophosphate-activated protein kinase; CAT: catalase; GDF15: growth differentiation factor 15; GSH-Px: glutathione peroxidase; IGF-1: insulin-like factor-1; PGC-1α: peroxisome proliferator-activated receptor γ coactivator (PPARγ)-1α; PI3K: phosphatidylinositol 3 kinase; mTOR: mammalian target of rapamycin; MyoD: myogenic differentiation factor D; Myf5: myogenic factor 5; MyoD: myogenic differentiation; NO: nitric oxide; UPS: ubiquitin-proteasome system; VEGF: vascular endothelial growth factor; ROS: reactive oxygen species; SCs: satellite cells; SOD: superoxide dismutase; TNF-α: tumor necrosis factor-α

Fig. 6

Exerkines (including cytokines and gut microbiome-related target molecules) are involved in exercise-induced beneficial effects via exosome-mediated cross-talk between distant organs and muscle, which are new mechanisms of exercise protecting skeletal muscle. The discovery of organ-derived new exerkines and their complex network interaction will be conducive to comprehensively investigating the mechanisms of exercise-induced protection of muscle. With the deepening of life science, sports science and medical research, spatial transcriptomics (emerging from phenotypes and metabolomics development) and the spatial multi-omics (forming by spatial transcriptomics and spatial proteomics) will provide more possibilities to clarify the mechanisms of protection for skeletal muscle comprehensively.

Funding

This research was funded by 10.13039/501100001809 National Natural Science Foundation of China , grant number “32171128 ”.

Submission statement

I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously and not under consideration for publication elsewhere, in whole or in part.

Conflict of interest

Zhenjun Tian is an editorial board member for Sports Medicine and Health Science and was not involved in the editorial review or the decision to publish this article. The authors have no financial or proprietary interests in any material discussed in this article. No conflict different exists in the submission of this manuscript, and manuscript is approved by all authors for publication.

Authors' contribution

Lili Feng: Writing – original draft, Conceptualization. Bowen Li: Writing – review & editing, Supervision. Su Sean Yong: Writing – review & editing, Supervision. Xiaonan Wu: Writing – review & editing. Zhenjun Tian: Writing – review & editing, Supervision, Conceptualization.

Acknowledgements

We thank the editors and reviewers of Sports Medicine and Health Science for supporting open science and hard work. We also thank the National Natural Science Foundation of China Grants (32171128 to Z.J., Tian).
==== Refs
References

1 Curcio F. Testa G. Liguori I. Sarcopenia and heart failure Nutrients 12 1 2020 211 10.3390/nu12010211 31947528
2 Ikemoto-Uezumi M. Zhou H. Kurosawa T. Increased MFG-E8 at neuromuscular junctions is an exacerbating factor for sarcopenia-associated denervation Aging Cell 21 1 2022 e13536 10.1111/acel.13536
3 Cruz-Jentoft A.J. Bahat G. Bauer J. Sarcopenia: revised European consensus on definition and diagnosis Age Ageing 48 1 2019 16 31 10.1093/ageing/afy169 30312372
4 Le Bacquer O. Salles J. Piscitelli F. Alterations of the endocannabinoid system and circulating and peripheral tissue levels of endocannabinoids in sarcopenic rats J Cachexia Sarcopenia Muscle 13 1 2022 662 676 10.1002/jcsm.12855 34854262
5 Cruz-Jentoft A.J. Sayer A.A. Sarcopenia Lancet 393 10191 2019 2636 2646 10.1016/s0140-6736(19)31138-9 31171417
6 Brzeszczyńska J. Brzeszczyński F. Hamilton D.F. McGregor R. Simpson A. Role of microRNA in muscle regeneration and diseases related to muscle dysfunction in atrophy, cachexia, osteoporosis, and osteoarthritis Bone Joint Res 9 11 2020 798 807 10.1302/2046-3758.911.Bjr-2020-0178.R1 33174473
7 Jeanmaire C. Mazières B. Verrouil E. Bernard L. Guillemin F. Rat A.C. Body composition and clinical symptoms in patients with hip or knee osteoarthritis: Results from the KHOALA cohort Semin Arthritis Rheum 47 6 2018 797 804 10.1016/j.semarthrit.2017.10.012 29224976
8 Mochizuki T. Yano K. Ikari K. Okazaki K. Sarcopenia-associated factors in Japanese patients with rheumatoid arthritis: A cross-sectional study Geriatr Gerontol Int 19 9 2019 907 912 10.1111/ggi.13747 31342647
9 Torii M. Hashimoto M. Hanai A. Prevalence and factors associated with sarcopenia in patients with rheumatoid arthritis Mod Rheumatol 29 4 2019 589 595 10.1080/14397595.2018.1510565 30092163
10 Kim K. Anderson E.M. Scali S.T. Ryan T.E. Skeletal muscle mitochondrial dysfunction and oxidative stress in peripheral arterial disease: A unifying mechanism and therapeutic target Antioxidants 9 12 2020 1304 10.3390/antiox9121304 33353218
11 Gortan Cappellari G. Aleksova A. Dal Ferro M. Preserved skeletal muscle mitochondrial function, redox state, inflammation and mass in obese mice with chronic heart failure Nutrients 12 11 2020 3393 10.3390/nu12113393 33158222
12 Moon J.H. Koo B.K. Kim W. Non-alcoholic fatty liver disease and sarcopenia additively increase mortality: a Korean nationwide survey J Cachexia Sarcopenia Muscle 12 4 2021 964 972 10.1002/jcsm.12719 34080327
13 Habig G. Smaltz C. Halegoua-DeMarzio D. Presence and implications of sarcopenia in non-alcoholic steatohepatitis Metabolites 11 4 2021 242 10.3390/metabo11040242 33920751
14 Zhang X. Trevino M.B. Wang M. Impaired mitochondrial energetics characterize poor early recovery of muscle mass following hind limb unloading in old mice J Gerontol A Biol Sci Med Sci 73 10 2018 1313 1322 10.1093/gerona/gly051 29562317
15 Armstrong V.S. Fitzgerald L.W. Bathe O.F. Cancer-associated muscle wasting-candidate mechanisms and molecular pathways Int J Mol Sci 21 23 2020 9268 10.3390/ijms21239268 33291708
16 Bozzetti F. Chemotherapy-induced sarcopenia Curr Treat Options Oncol 21 1 2020 7 10.1007/s11864-019-0691-9 32002684
17 Dhillon R.J. Hasni S. Pathogenesis and management of sarcopenia Clin Geriatr Med 33 1 2017 17 26 10.1016/j.cger.2016.08.002 27886695
18 Lim S.L. Liu X. Gao Q. Subclinical vasculopathy and skeletal muscle metrics in the singapore longitudinal ageing study Aging 13 11 2021 14768 14784 10.18632/aging.203142 34096885
19 Mizuno T. Matsui Y. Tomida M. Differences in the mass and quality of the quadriceps with age and sex and their relationships with knee extension strength J Cachexia Sarcopenia Muscle 12 4 2021 900 912 10.1002/jcsm.12715 34009738
20 Bagheri A. Hashemi R. Heshmat R. Motlagh A.D. Esmaillzadeh A. Patterns of nutrient intake in relation to sarcopenia and its components Front Nutr 8 2021 645072 10.3389/fnut.2021.645072
21 Alhussain M.H. Alkahtani S. Aljuhani O. Habib S.S. Effects of nutrient intake on diagnostic measures of sarcopenia among arab men: a cross-sectional study Nutrients 13 1 2020 114 10.3390/nu13010114 33396961
22 Nikolov J. Norman K. Buchmann N. Association between meal-specific daily protein intake and lean mass in older adults: results of the cross-sectional BASE-II study Am J Clin Nutr 114 3 2021 1141 1147 10.1093/ajcn/nqab144 33963728
23 Akehurst E. Scott D. Rodriguez J.P. Associations of sarcopenia components with physical activity and nutrition in Australian older adults performing exercise training BMC Geriatr 21 1 2021 276 10.1186/s12877-021-02212-y 33902464
24 Li C. Kang B. Zhang T. Dietary pattern and dietary energy from fat associated with sarcopenia in community-dwelling older Chinese people: a cross-sectional study in three regions of China Nutrients 12 12 2020 3689 10.3390/nu12123689 33265923
25 Prokopidis K. Witard O.C. Understanding the role of smoking and chronic excess alcohol consumption on reduced caloric intake and the development of sarcopenia Nutr Res Rev 35 2 2022 197 206 10.1017/s0954422421000135 34027849
26 Aoyama S. Nakahata Y. Shinohara K. Chrono-nutrition has potential in preventing age-related muscle loss and dysfunction Front Neurosci 15 2021 659883 10.3389/fnins.2021.659883
27 Chen Z. Li W.Y. Ho M. Chau P.H. The prevalence of sarcopenia in Chinese older adults: meta-analysis and meta-regression Nutrients 13 5 2021 1441 10.3390/nu13051441 33923252
28 Welch C. Majid Z. Greig C. Gladman J. Masud T. Jackson T. Interventions to ameliorate reductions in muscle quantity and function in hospitalised older adults: a systematic review towards acute sarcopenia treatment Age Ageing 50 2 2021 394 404 10.1093/ageing/afaa209 33098419
29 De Spiegeleer A. Beckwée D. Bautmans I. Petrovic M. Pharmacological interventions to improve muscle mass, muscle strength and physical performance in older people: an umbrella review of systematic reviews and meta-analyses Drugs Aging 35 8 2018 719 734 10.1007/s40266-018-0566-y 30047068
30 Gkekas N.K. Anagnostis P. Paraschou V. The effect of vitamin D plus protein supplementation on sarcopenia: a systematic review and meta-analysis of randomized controlled trials Maturitas 145 2021 56 63 10.1016/j.maturitas.2021.01.002 33541563
31 Parahiba S.M. Ribeiro É C.T. Corrêa C. Bieger P. Perry I.S. Souza G.C. Effect of testosterone supplementation on sarcopenic components in middle-aged and elderly men: a systematic review and meta-analysis Exp Gerontol 142 2020 111106 10.1016/j.exger.2020.111106
32 Markofski M.M. Jennings K. Timmerman K.L. Effect of aerobic exercise training and essential amino acid supplementation for 24 Weeks on physical function, body composition, and muscle metabolism in healthy, independent older adults: a randomized clinical trial J Gerontol A Biol Sci Med Sci 74 10 2019 1598 1604 10.1093/gerona/gly109 29750251
33 Thomas D.T. Schnell D.M. Redzic M. Local in vivo measures of muscle lipid and oxygen consumption change in response to combined vitamin D repletion and aerobic training in older adults Nutrients 11 4 2019 930 10.3390/nu11040930 31027191
34 MacDonald T.L. Pattamaprapanont P. Cooney E.M. Canagliflozin prevents hyperglycemia-associated muscle extracellular matrix accumulation and improves the adaptive response to aerobic exercise Diabetes 71 5 2022 881 893 10.2337/db21-0934 35108373
35 Dvoretskiy S. Lieblein-Boff J.C. Jonnalagadda S. Atherton P.J. Phillips B.E. Pereira S.L. Exploring the association between vascular dysfunction and skeletal muscle mass, strength and function in healthy adults: a systematic review Nutrients 12 3 2020 715 10.3390/nu12030715 32156061
36 Zizola C. Kennel P.J. Akashi H. Activation of PPARδ signaling improves skeletal muscle oxidative metabolism and endurance function in an animal model of ischemic left ventricular dysfunction Am J Physiol Heart Circ Physiol 308 9 2015 H1078 H1085 10.1152/ajpheart.00679.2014 25713305
37 Cui D. Drake J.C. Wilson R.J. A novel voluntary weightlifting model in mice promotes muscle adaptation and insulin sensitivity with simultaneous enhancement of autophagy and mTOR pathway FASEB J 34 6 2020 7330 7344 10.1096/fj.201903055R 32304342
38 Koeppel M. Mathis K. Schmitz K.H. Wiskemann J. Muscle hypertrophy in cancer patients and survivors via strength training. A meta-analysis and meta-regression Crit Rev Oncol Hematol 163 2021 103371 10.1016/j.critrevonc.2021.103371
39 Yuan Y. Xu P. Jiang Q. Exercise-induced α-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation EMBO J 40 14 2021 e108434 10.15252/embj.2021108434
40 Snijders T. Holwerda A.M. van Loon L.J.C. Verdijk L.B. Myonuclear content and domain size in small versus larger muscle fibres in response to 12 weeks of resistance exercise training in older adults Acta Physiol 231 4 2021 e13599 10.1111/apha.13599
41 van de Bool C. Rutten E.P.A. van Helvoort A. Franssen F.M.E. Wouters E.F.M. Schols A.M.W.J. A randomized clinical trial investigating the efficacy of targeted nutrition as adjunct to exercise training in COPD J Cachexia Sarcopenia Muscle 8 5 2017 748 758 10.1002/jcsm.12219 28608438
42 Ghasemikaram M. Engelke K. Kohl M. von Stengel S. Kemmler W. Detraining effects on muscle quality in older men with osteosarcopenia. Follow-up of the randomized controlled franconian osteopenia and sarcopenia trial (FrOST) Nutrients 13 5 2021 1528 10.3390/nu13051528 34062828
43 Blackwell J.E.M. Gharahdaghi N. Brook M.S. The physiological impact of high-intensity interval training in octogenarians with comorbidities 12 4 2021 866 879 10.1002/jcsm.12724
44 Feng L. Li B. Tian Z. Exerkines: opening the way to protecting ischemic heart Curr Opin Physiol 31 2023 100615 10.1016/j.cophys.2022.100615
45 Marzuca-Nassr G.N. Artigas-Arias M. Olea M.A. High-intensity interval training on body composition, functional capacity and biochemical markers in healthy young versus older people Exp Gerontol 141 2020 111096 10.1016/j.exger.2020.111096
46 Batitucci G. Faria Junior E.V. Nogueira J.E. Impact of intermittent fasting combined with high-intensity interval training on body composition, metabolic biomarkers, and physical fitness in women with obesity Front Nutr 9 2022 884305 10.3389/fnut.2022.884305 35694163
47 França G.O. Frantz E.D.C. Magliano D.C. Effects of short-term high-intensity interval and continuous exercise training on body composition and cardiac function in obese sarcopenic rats Life Sci 256 2020 117920 10.1016/j.lfs.2020.117920
48 Wadsworth D. Lark S. Effects of whole-body vibration training on the physical function of the frail elderly: an open, randomized controlled trial Arch Phys Med Rehabil 101 7 2020 1111 1119 10.1016/j.apmr.2020.02.009 32145279
49 Wei N. Ng G.Y.F. The effect of whole body vibration training on quadriceps voluntary activation level of people with age-related muscle loss (sarcopenia): a randomized pilot study BMC Geriatr 18 1 2018 240 10.1186/s12877-018-0923-z 30305044
50 Chang S.F. Lin P.C. Yang R.S. Yang R.J. The preliminary effect of whole-body vibration intervention on improving the skeletal muscle mass index, physical fitness, and quality of life among older people with sarcopenia BMC Geriatr 18 1 2018 17 10.1186/s12877-018-0712-8 29343219
51 Machado A. Garcia-Lopez D. Gonzalez-Gallego J. Garatachea N. Whole-body vibration training increases muscle strength and mass in older women: a randomized-controlled trial Scand J Med Sci Sports 20 2 2010 200 207 10.1111/j.1600-0838.2009.00919.x 19422657
52 Teschler M. Heimer M. Schmitz B. Kemmler W. Mooren F.C. Four weeks of electromyostimulation improves muscle function and strength in sarcopenic patients: a three-arm parallel randomized trial J Cachexia Sarcopenia Muscle 12 4 2021 843 854 10.1002/jcsm.12717 34105256
53 Kemmler W. von Stengel S. Whole-body electromyostimulation as a means to impact muscle mass and abdominal body fat in lean, sedentary, older female adults: subanalysis of the TEST-III trial Clin Interv Aging 8 2013 1353 1364 10.2147/cia.S52337 24130433
54 Wittmann K. Sieber C. von Stengel S. Impact of whole body electromyostimulation on cardiometabolic risk factors in older women with sarcopenic obesity: the randomized controlled FORMOsA-sarcopenic obesity study Clin Interv Aging 11 2016 1697 1706 10.2147/cia.S116430 27920508
55 Davis J.A. Mohebbi M. Collier F. The role of diet quality and dietary patterns in predicting muscle mass and function in men over a 15-year period Osteoporos Int 32 11 2021 2193 2203 10.1007/s00198-021-06012-3 34043032
56 Otsuka Y. Iidaka T. Horii C. Dietary intake of vitamin E and fats associated with sarcopenia in community-dwelling older Japanese people: a cross-sectional study from the fifth survey of the road study Nutrients 13 5 2021 1730 10.3390/nu13051730 34065253
57 Park S. Chae M. Park H. Park K. Higher branched-chain amino acid intake is associated with handgrip strength among Korean older adults Nutrients 13 5 2021 1522 10.3390/nu13051522 33946360
58 Amirato G.R. Borges J.O. Marques D.L. L-glutamine supplementation enhances strength and power of knee muscles and improves glycemia control and plasma redox balance in exercising elderly women Nutrients 13 3 2021 1025 10.3390/nu13031025 33809996
59 Beckwee D. Delaere A. Aelbrecht S. Exercise interventions for the prevention and treatment of sarcopenia. A systematic umbrella review J Nutr Health Aging 23 6 2019 494 502 10.1007/s12603-019-1196-8 31233069
60 da Silva Goncalves L. Santos Lopes da Silva L. Rodrigues Benjamim C.J. The effects of different exercise training types on body composition and physical performance in older adults with sarcopenic obesity: a systematic review and meta-analysis J Nutr Health Aging 27 11 2023 1076 1090 10.1007/s12603-023-2018-6 37997730
61 Lai C.C. Tu Y.K. Wang T.G. Huang Y.T. Chien K.L. Effects of resistance training, endurance training and whole-body vibration on lean body mass, muscle strength and physical performance in older people: a systematic review and network meta-analysis Age Ageing 47 3 2018 367 373 10.1093/ageing/afy009 29471456
62 Liu X. Gao Y. Lu J. Effects of different resistance exercise forms on body composition and muscle strength in overweight and/or obese individuals: a systematic review and meta-analysis.Front Physiol 12 2022 791999 10.3389/fphys.2021.791999
63 Cruz-Jentoft A.J. Landi F. Schneider S.M. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS) Age Ageing 43 6 2014 748 759 10.1093/ageing/afu115 25241753
64 Gielen E. Beckwee D. Delaere A. Nutritional interventions to improve muscle mass, muscle strength, and physical performance in older people: an umbrella review of systematic reviews and meta-analyses Nutr Rev 79 2 2021 121 147 10.1093/nutrit/nuaa011 32483625
65 Nunes E.A. Colenso-Semple L. McKellar S.R. Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults submitted for publication J Cachexia Sarcopenia Muscle 13 2 2022 795 810 10.1002/jcsm.12922 35187864
66 Figueroa A. Jaime S.J. Morita M. Ju Gonzales Moinard C. L-citrulline supports vascular and muscular benefits of exercise training in older adults Exerc Sport Sci Rev 48 3 2020 133 139 10.1249/jes.0000000000000223 32568925
67 Tickle P.G. Hendrickse P.W. Weightman A. Nazir M.H. Degens H. Egginton S. Impaired skeletal muscle fatigue resistance during cardiac hypertrophy is prevented by functional overload- or exercise-induced functional capillarity J Physiol 599 15 2021 3715 3733 10.1113/jp281377 34107075
68 Tryfonos A. Tzanis G. Pitsolis T. Exercise training enhances angiogenesis-related gene responses in skeletal muscle of patients with chronic heart failure Cells 10 8 2021 1915 10.3390/cells10081915 34440684
69 Leuchtmann A.B. Mueller S.M. Aguayo D. Resistance training preserves high-intensity interval training induced improvements in skeletal muscle capillarization of healthy old men: a randomized controlled trial Sci Rep 10 1 2020 6578 10.1038/s41598-020-63490-x 32313031
70 Nederveen J.P. Betz M.W. Snijders T. Parise G. The importance of muscle capillarization for optimizing satellite cell plasticity Exerc Sport Sci Rev 49 4 2021 284 290 10.1249/jes.0000000000000270 34547761
71 Nederveen J.P. Joanisse S. Snijders T. Skeletal muscle satellite cells are located at a closer proximity to capillaries in healthy young compared with older men J Cachexia Sarcopenia Muscle 7 5 2016 547 554 10.1002/jcsm.12105 27239425
72 Moro T. Brightwell C.R. Volpi E. Rasmussen B.B. Fry C.S. Resistance exercise training promotes fiber type-specific myonuclear adaptations in older adults J Appl Physiol 128 4 2020 795 804 10.1152/japplphysiol.00723.2019 32134710
73 Chow L.S. Gerszten R.E. Taylor J.M. Exerkines in health, resilience and disease Nat Rev Endocrinol 18 5 2022 273 289 10.1038/s41574-022-00641-2 35304603
74 Heo J. Noble E.E. Call J.A. The role of exerkines on brain mitochondria: a mini-review J Appl Physiol (1985) 134 1 2023 28 35 10.1152/japplphysiol.00565.2022 36417200
75 Kim H. Kim K.M. Kang M.J. Lim S. Growth differentiation factor-15 as a biomarker for sarcopenia in aging humans and mice Exp Gerontol 142 2020 111115 10.1016/j.exger.2020.111115
76 Feng L. Li B. Xi Y. Cai M. Tian Z. Aerobic exercise and resistance exercise alleviate skeletal muscle atrophy through IGF-1/IGF-1R-PI3K/Akt pathway in mice with myocardial infarction Am J Physiol Cell Physiol 322 2 2022 C164 C176 10.1152/ajpcell.00344.2021 34852207
77 Ren W. Xu Z. Pan S. Irisin and ALCAT1 mediated aerobic exercise-alleviated oxidative stress and apoptosis in skeletal muscle of mice with myocardial infarction Free Radic Biol Med 193(Pt 2) 2022 526 537 10.1016/j.freeradbiomed.2022.10.321 36336228
78 Shirvani H. Rahmati-Ahmadabad S. Kowsari E. Fry H. Kazemi M. Kaviani M. Effects of 2-week HMB-FA supplementation with or without eccentric resistance exercise on expression of some genes related to muscle protein turnover and serum irisin and IGF-1 concentrations Gene 760 2020 145018 10.1016/j.gene.2020.145018
79 Ahn J. Son H.J. Seo H.D. γ-Oryzanol improves exercise endurance and muscle strength by upregulating PPARδ and ERRγ activity in aged mice Mol Nutr Food Res 65 14 2021 e2000652 10.1002/mnfr.202000652
80 Wang B. Zhang C. Zhang A. Cai H. Price S.R. Wang X.H. MicroRNA-23a and MicroRNA-27a mimic exercise by ameliorating CKD-induced muscle atrophy J Am Soc Nephrol 28 9 2017 2631 2640 10.1681/asn.2016111213 28400445
81 Liu Q. Chen L. Liang X. Exercise attenuates angiotensinⅡ-induced muscle atrophy by targeting PPARγ/miR-29b J Sport Health Sci 11 6 2022 696 707 10.1016/j.jshs.2021.06.002 34116237
82 Margolis L.M. Carrigan C.T. Murphy N.E. Carbohydrate intake in recovery from aerobic exercise differentiates skeletal muscle microRNA expression Am J Physiol Endocrinol Metab 323 5 2022 E435 E447 10.1152/ajpendo.00110.2022 36044708
83 Giron M. Thomas M. Dardevet D. Chassard C. Savary-Auzeloux I. Gut microbes and muscle function: can probiotics make our muscles stronger? J Cachexia Sarcopenia Muscle 13 3 2022 1460 1476 10.1002/jcsm.12964 35278043
84 Sakakida T. Ishikawa T. Doi T. Water-soluble dietary fiber alleviates cancer-induced muscle wasting through changes in gut microenvironment in mice Cancer Sci 113 5 2022 1789 1800 10.1111/cas.15306 35201655
85 Hood D.A. Memme J.M. Oliveira A.N. Triolo M. Maintenance of Skeletal Muscle Mitochondria in Health, Exercise, and Aging Annu Rev Physiol 81 2019 19 41 10.1146/annurev-physiol-020518-114310 30216742
86 Sahm A. Bens M. Platzer M. Cellerino A. Parallel evolution of genes controlling mitonuclear balance in short-lived annual fishes Aging Cell 16 3 2017 488 496 10.1111/acel.12577 28295945
87 Jia D. Tian Z. Wang R. Exercise mitigates age-related metabolic diseases by improving mitochondrial dysfunction Ageing Res Rev 91 2023 102087 10.1016/j.arr.2023.102087 37832607
88 Sen B. Rastogi A. Nath R. Senescent hepatocytes in decompensated liver show reduced UPRMT and its key player, CLPP, attenuates senescence in vitro Cell Mol Gastroenterol Hepatol 8 1 2019 73 94 10.1016/j.jcmgh.2019.03.001 30878663
89 Li J. Yu D. Chen S. Sirt6 opposes glycochenodeoxycholate-induced apoptosis of biliary epithelial cells through the AMPK/PGC-1α pathway Cell Biosci 10 1 2020 43 10.1186/s13578-020-00402-6 32206298
90 Hingst J.R. Kjobsted R. Birk J.B. Inducible deletion of skeletal muscle AMPKα reveals that AMPK is required for nucleotide balance but dispensable for muscle glucose uptake and fat oxidation during exercise Mol Metabol 40 2020 101028 10.1016/j.molmet.2020.101028
91 Head S.A. Shi W. Zhao L. Antifungal drug itraconazole targets VDAC1 to modulate the AMPK/mTOR signaling axis in endothelial cells Proc Natl Acad Sci U S A 112 52 2015 E7276 E7285 10.1073/pnas.1512867112 26655341
92 Xu D.Q. Li C.J. Jiang Z.Z. The hypoglycemic mechanism of catalpol involves increased AMPK-mediated mitochondrial biogenesis Acta Pharmacol Sin 41 6 2020 791 799 10.1038/s41401-019-0345-2 31937931
93 Kjobsted R. Hingst J.R. Fentz J. AMPK in skeletal muscle function and metabolism FASEB J 32 4 2018 1741 1777 10.1096/fj.201700442R 29242278
94 Fu Z.J. Wang Z.Y. Xu L. HIF-1α-BNIP3-mediated mitophagy in tubular cells protects against renal ischemia/reperfusion injury Redox Biol 36 2020 101671 10.1016/j.redox.2020.101671 32829253
95 Parousis A. Carter H.N. Tran C. Contractile activity attenuates autophagy suppression and reverses mitochondrial defects in skeletal muscle cells Autophagy 14 11 2018 1886 1897 10.1080/15548627.2018.1491488 30078345
96 Mader T. Chaillou T. Alves E.S. Exercise reduces intramuscular stress and counteracts muscle weakness in mice with breast cancer J Cachexia Sarcopenia Muscle 13 2 2022 1151 1163 10.1002/jcsm.12944 35170227
97 Wei W. Ruvkun G. Lysosomal activity regulates Caenorhabditis elegans mitochondrial dynamics through vitamin B12 metabolism Proc Natl Acad Sci U S A 117 33 2020 19970 19981 10.1073/pnas.2008021117 32737159
98 Wang Y. Li J. Zhang Z. Wang R. Bo H. Zhang Y. Exercise improves the coordination of the mitochondrial unfolded protein response and mitophagy in aging skeletal muscle Life (Basel) 13 4 2023 1006 10.3390/life13041006 37109535
99 Memme J.M. Erlich A.T. Hood D.A. Phukan G. Exercise and mitochondrial health J Physiol 599 3 2021 803 817 10.1113/jp278853 31674658
100 Gomes M.J. Pagan L.U. Lima A.R.R. Effects of aerobic and resistance exercise on cardiac remodelling and skeletal muscle oxidative stress of infarcted rats J Cell Mol Med 24 9 2020 5352 5362 10.1111/jcmm.15191 32239667
101 Liang J. Zhang H. Zeng Z. Lifelong aerobic exercise alleviates sarcopenia by activating autophagy and inhibiting protein degradation via the AMPK/PGC-1α signaling pathway Metabolites 11 5 2021 323 10.3390/metabo11050323 34069829
102 Cesare M.M. Felice F. Santini V. Di Stefano R. Antioxidants in sport sarcopenia Nutrients 12 9 2020 2869 10.3390/nu12092869 32961753
103 Aquila G. Re Cecconi A.D. Brault J.J. Corli O. Piccirillo R. Nutraceuticals and exercise against muscle wasting during cancer cachexia Cells 9 12 2020 2536 10.3390/cells9122536 33255345
104 Liu S. Meng F. Zhang D. Lonicera caerulea berry polyphenols extract alleviates exercise fatigue in mice by reducing oxidative stress, inflammation, skeletal muscle cell apoptosis, and by increasing cell proliferation Front Nutr 9 2022 853225 10.3389/fnut.2022.853225
105 Bose C. Alves I. Singh P. Sulforaphane prevents age-associated cardiac and muscular dysfunction through Nrf2 signaling Aging Cell 19 11 2020 e13261 10.1111/acel.13261
106 Kim J.H. Lee Y. Kwak H.B. Lawler J.M. Lifelong wheel running exercise and mild caloric restriction attenuate nuclear EndoG in the aging plantaris muscle Exp Gerontol 69 2015 122 128 10.1016/j.exger.2015.06.007 26055450
107 Ahn J. Kim M.J. Yoo A. Identifying Codium fragile extract components and their effects on muscle weight and exercise endurance Food Chem 353 2021 129463 10.1016/j.foodchem.2021.129463
108 Nikooie R. Jafari-Sardoie S. Sheibani V. Nejadvaziri Chatroudi A. Resistance training-induced muscle hypertrophy is mediated by TGF-β1-Smad signaling pathway in male Wistar rats J Cell Physiol 235 7–8 2020 5649 5665 10.1002/jcp.29497 31960436
109 Chen Z. Li L. Wu W. Exercise protects proliferative muscle satellite cells against exhaustion via the Igfbp7-Akt-mTOR axis Theranostics 10 14 2020 6448 6466 10.7150/thno.43577 32483463
110 Hsu W.B. Lin S.J. Hung J.S. Effect of resistance training on satellite cells in old mice - a transcriptome study : implications for sarcopenia Bone Joint Res 11 2 2022 121 133 10.1302/2046-3758.112.Bjr-2021-0079.R2 35188421
111 Fu S. Lin X. Yin L. Wang X. Androgen receptor regulates the proliferation of myoblasts under appropriate or excessive stretch through IGF-1 receptor mediated p38 and ERK1/2 pathways Nutr Metab 18 1 2021 85 10.1186/s12986-021-00610-y
112 Li B. Feng L. Wu X. Cai M. Yu J.J. Tian Z. Effects of different modes of exercise on skeletal muscle mass and function and IGF-1 signaling during early aging in mice J Exp Biol 225 21 2022 jeb244650 10.1242/jeb.244650 36205111
113 Fujimaki S. Hidaka R. Asashima M. Takemasa T. Kuwabara T. Wnt protein-mediated satellite cell conversion in adult and aged mice following voluntary wheel running J Biol Chem 289 11 2014 7399 7412 10.1074/jbc.M113.539247 24482229
114 Brooks M.J. Hajira A. Mohamed J.S. Alway S.E. Voluntary wheel running increases satellite cell abundance and improves recovery from disuse in gastrocnemius muscles from mice J Appl Physiol (1985) 124 6 2018 1616 1628 10.1152/japplphysiol.00451.2017 29470148
115 Steyn P.J. Dzobo K. Smith R.I. Myburgh K.H. Interleukin-6 induces myogenic differentiation via JAK2-STAT3 signaling in mouse C2C12 myoblast cell line and primary human myoblasts Int J Mol Sci 20 21 2019 5273 10.3390/ijms20215273 31652937
116 Gould D.W. Lahart I. Carmichael A.R. Koutedakis Y. Metsios G.S. Cancer cachexia prevention via physical exercise: molecular mechanisms J Cachexia Sarcopenia Muscle 4 2 2013 111 124 10.1007/s13539-012-0096-0 23239116
117 Viana J.L. Kosmadakis G.C. Watson E.L. Evidence for anti-inflammatory effects of exercise in CKD J Am Soc Nephrol 25 9 2014 2121 2130 10.1681/asn.2013070702 24700875
118 Fabersani E. Claudia Abeijon-Mukdsi M. Ross R. Medina R. Gonzalez S. Gauffin-Cano P. Specific strains of lactic acid bacteria differentially modulate the profile of adipokines in vitro.Front Immunol 8 2017 266 10.3389/fimmu.2017.00266
119 Wolf J. Rose-John S. Garbers C. Interleukin-6 and its receptors: a highly regulated and dynamic system Cytokine 70 1 2014 11 20 10.1016/j.cyto.2014.05.024 24986424
120 Cao X.L. Zhou X.Y. Xu N.X. Chen S.C. Xu C.M. Association of IL-4 and IL-10 polymorphisms with preterm birth susceptibility: a systematic review and meta-analysis Front Immunol 13 2022 917383 10.3389/fimmu.2022.917383 35860261
121 Fernandes P. Oliveira LdM. Bruggemann T.R. Sato M.N. Olivo C.R. Arantes-Costa F.M. Physical exercise induces immunoregulation of TREG, M2, and pDCs in a lung allergic inflammation model Front Immunol 10 2019 854 10.3389/fimmu.2019.00854 31156611
122 Belo G.A. Cordeiro B.F. Oliveira E.R. SlpB protein enhances the probiotic potential of L. lactis NCDO 2118 in colitis mice model Front Pharmacol 12 2021 755825 10.3389/fphar.2021.755825 34987390
123 Rai S. Grockowiak E. Hansen N. Inhibition of interleukin-1β reduces myelofibrosis and osteosclerosis in mice with JAK2-V617F driven myeloproliferative neoplasm Nat Commun 13 1 2022 5346 10.1038/s41467-022-32927-4 36100613
124 Shivakoti R. Biggs M.L. Djousse L. Intake and sources of dietary fiber, inflammation, and cardiovascular disease in older US adults JAMA Netw Open 5 3 2022 e225012 10.1001/jamanetworkopen.2022.5012
125 Chen D. Li J. Huang Y. Interleukin 13 promotes long-term recovery after ischemic stroke by inhibiting the activation of STAT3 J Neuroinflammation 19 1 2022 112 10.1186/s12974-022-02471-5 35578342
126 Dhital S. Rice C.D. Vyavahare N.R. Reversal of elastase-induced abdominal aortic aneurysm following the delivery of nanoparticle-based pentagalloyl glucose (PGG) is associated with reduced inflammatory and immune markers Eur J Pharmacol 910 2021 174487 10.1016/j.ejphar.2021.174487 34516951
127 Uzeloto J.S. de Toledo-Arruda A.C. Silva B.S.A. Effect of physical training on cytokine expression in CD4+T lymphocytes in subjects with stable COPD Ther Adv Respir Dis 16 2022 10.1177/17534666221091179
128 Lacerda D.R. Nunes-Silva A. Silveira A.L.M. Acute exercise modulates the inflammatory response in adipose tissue in both lean and obese mice Nutrition 115 2023 112092 10.1016/j.nut.2023.112092 37549454
129 Cao Y. Li Y. Han W. Sodium butyrate ameliorates type 2 diabetes-related sarcopenia through IL-33-independent ILC2s/IL-13/STAT3 signaling pathway J Inflamm Res 16 2023 343 358 10.2147/jir.S392350 36733489
130 Cho J. Choi Y. Sajgalik P. Exercise as a therapeutic strategy for sarcopenia in heart failure: insights into underlying mechanisms Cells 9 10 2020 2284 10.3390/cells9102284 33066240
131 Gao H.E. Wu D.S. Sun L. Effects of lifelong exercise on age-related body composition, oxidative stress, inflammatory cytokines, and skeletal muscle proteome in rats Mech Ageing Dev 189 2020 111262 10.1016/j.mad.2020.111262
132 Morawin B. Tylutka A. Chmielowiec J. Zembron-Lacny A. Circulating mediators of apoptosis and inflammation in aging; physical exercise intervention Int J Environ Res Public Health 18 6 2021 3165 10.3390/ijerph18063165 33808526
133 Zhang Z. Cui D. Zhang T. Sun Y. Ding S. Swimming differentially affects t2dm-induced skeletal muscle ER stress and mitochondrial dysfunction related to MAM Diabetes Metab Syndr Obes 13 2020 1417 1428 10.2147/dmso.S243024 32431525
134 Smeuninx B. Elhassan Y.S. Manolopoulos K.N. The effect of short-term exercise prehabilitation on skeletal muscle protein synthesis and atrophy during bed rest in older men J Cachexia Sarcopenia Muscle 12 1 2021 52 69 10.1002/jcsm.12661 33347733
135 Colleluori G. Aguirre L. Phadnis U. Aerobic plus resistance exercise in obese older adults improves muscle protein synthesis and preserves myocellular quality despite weight loss Cell Metabol 30 2 2019 261 273.e6 10.1016/j.cmet.2019.06.008
136 Cruz-Jentoft A.J. Dawson Hughes B. Scott D. Sanders K.M. Rizzoli R. Nutritional strategies for maintaining muscle mass and strength from middle age to later life: a narrative review Maturitas 132 2020 57 64 10.1016/j.maturitas.2019.11.007 31883664
137 Holwerda A.M. Paulussen K.J.M. Overkamp M. Leucine coingestion augments the muscle protein synthetic response to the ingestion of 15 g of protein following resistance exercise in older men Am J Physiol Endocrinol Metab 317 3 2019 E473 E482 10.1152/ajpendo.00073.2019 31112406
138 Sahebkar A. Cicero A.F.G. Di Giosia P. Pathophysiological mechanisms of statin-associated myopathies: possible role of the ubiquitin-proteasome system Journal of cachexia, sarcopenia and muscle 11 5 2020 1177 1186 10.1002/jcsm.12579 32743965
139 Pallafacchina G. Blaauw B. Schiaffino S. Role of satellite cells in muscle growth and maintenance of muscle mass Nutr Metab Cardiovasc Dis 23 Suppl 1 2013 S12 S18 10.1016/j.numecd.2012.02.002 22621743
140 Nederveen J.P. Joanisse S. Snijders T. Thomas A.C.Q. Kumbhare D. Parise G. The influence of capillarization on satellite cell pool expansion and activation following exercise-induced muscle damage in healthy young men J Physiol 596 6 2018 1063 1078 10.1113/jp275155 29315567
141 Masschelein E. D’Hulst G. Zvick J. Exercise promotes satellite cell contribution to myofibers in a load-dependent manner Skeletal Muscle 10 1 2020 21 10.1186/s13395-020-00237-2 32646489
142 Snijders T. Nederveen J.P. Bell K.E. Prolonged exercise training improves the acute type II muscle fibre satellite cell response in healthy older men J Physiol 597 1 2019 105 119 10.1113/jp276260 30370532
143 Gil S. Kirwan J.P. Murai I.H. A randomized clinical trial on the effects of exercise on muscle remodelling following bariatric surgery J Cachexia Sarcopenia Muscle 12 6 2021 1440 1455 10.1002/jcsm.12815 34666419
144 Abreu P. Kowaltowski A.J. Satellite cell self-renewal in endurance exercise is mediated by inhibition of mitochondrial oxygen consumption J Cachexia Sarcopenia Muscle 11 6 2020 1661 1676 10.1002/jcsm.12601 32748470
145 Yamamoto A. Honda S. Ogura M. Lemon myrtle (backhousia citriodora) extract and its active compound, casuarinin, activate skeletal muscle satellite cells in vitro and in vivo Nutrients 14 5 2022 1078 10.3390/nu14051078 35268053
