==== Front
Innov Aging
Innov Aging
innovateage
Innovation in Aging
2399-5300 Oxford University Press US 

10.1093/geroni/igaa057.1673
igaa057.1673
Abstracts
Session 3018 (Symposium)
ESPO/ Biological Sciences Section Symposium: Understanding the Complex and Interconnected Pathways of Aging
AcademicSubjects/SOC02600
Sex Differences in Response to Metformin in a Longitudinal Study in Mice
Teixeira Camila Vieira Ligo 1 Alfaras Irene 2 Camadola Simonetta 1 Price Nathan 3 Bernier Michel 1 de Cabo Rafael 1 1 
National Institute on Aging,, Baltimore, Maryland, United States
2 
University of Pittsburgh, Pittsburgh, Pennsylvania, United States
3 
Yale University, New Haven, Connecticut, United States
2020 
16 12 2020 
16 12 2020 
4 Suppl 1 Program Abstracts from The GSA 2020 Annual Scientific Meeting “Turning 75: Why Age Matters”518 518
© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.2020This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract
Sexual dimorphisms have been recognized in most aspects of human health and disease, and there is now clear evidence for more pronounced differences in response to pharmacological interventions of aging. Here, male and female C57BL/6J mice at six months of age were administered 0.5% metformin in their diet every-other-week (EOW) for the remainder of their lives. The intervention was well tolerated and did not result in lifespan extension. Male mice treated with metformin EOW lost weight and augmented lean-to-fat ratio. In contrast, EOW females were refractory to changes in body weight and body composition compared to controls. The intervention did not influence non-fasted plasma glucose levels, while causing an increase in lactate in mice of both sexes. Indirect calorimetry was performed to measure energy expenditure in EOW mice that were either ON or OFF metformin during testing. Focusing on the respiratory exchange ratio (RER), males, but not females, preferentially utilized carbohydrates (RER ~0.9-1.0) when OFF metformin, switching to lipids (RER ~0.8-0.9) when ON metformin. This resulted in significant differences compared to controls in both periods (OFF and ON). RER of EOW females was different from controls during OFF metformin (RER ~0.8-0.9), while exhibiting significantly lower RER when ON metformin (RER ~0.7-0.8). These results clearly point at a strong dimorphism in the action of metformin in mice, including its role in metabolic homeostasis and overall health span. A better understanding of how sex influences the health and prolongevity benefits of metformin will benefit our understanding of the longterm clinical implications.