The evolution and ontogeny of lifespan at the species and individual level, the energetics of the organism in its environment, the storage of metabolizable energy as body fat, and socioeconomic disparities within populations all seem intricately related and yet the nature of these interrelations is poorly understood. Indeed questions as fundamental as why we age remain open and subsidiary questions such as why caloric restriction leads to increased lifespan and why lower socioeconomic status is related to obesity in developed countries also remain unanswered. Herein, we propose a unified model informed by evolutionary thinking about life strategies which connects these phenomena. In this model, aging or more precisely senescence is not something that passively happens to us as the result of environmental insults or from metabolizing fuel, but is something we do. That is, mortality rate or the rate of aging is seen as (partially) internally regulable phenomenon much like the control of body temperature in homeotherms in which the regulated rate is responsive to perceptions about the energetic state of the environment. From this perspective, it is perceptions of the energetic security of the environment that are a key factor in linking these phenomena. We elaborate this theory herein and from it derive seven specific hypotheses, each of which is testable in a different experiment using model organisms. We have assembled a team of the world's leading researchers to conduct these seven experiments and then to conduct follow-up work to study both a priori specified potential causal mechanisms involving internal clock regulation and also to conduct exploratory work to identify new potential mechanisms. Outcomes from this work will have profound implications for our understanding of the nature of aging, of health disparities, and of obesity.

Public Health Relevance

Maximizing quality of life for citizens from all social strata and at all ages requires an understanding of the factors that lead to disparities in health, to differences in body fat levels, and to healthier aging in our increasingly older population. The proposed research will contribute such knowledge.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BCMB-A (51))
Program Officer
Finkelstein, David B
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Alabama Birmingham
Schools of Public Health
United States
Zip Code
Harvanek, Zachary M; Mourão, Márcio A; Schnell, Santiago et al. (2016) A computational approach to studying ageing at the individual level. Proc Biol Sci 283:
Brewer, Rachel A; Gibbs, Victoria K; Smith Jr, Daniel L (2016) Targeting glucose metabolism for healthy aging. Nutr Healthy Aging 4:31-46
Austad, Steven N; Fischer, Kathleen E (2016) Sex Differences in Lifespan. Cell Metab 23:1022-33
Vaanholt, L M; Milne, A; Zheng, Y et al. (2016) Oxidative costs of reproduction: Oxidative stress in mice fed standard and low antioxidant diets. Physiol Behav 154:1-7
Gibbs, Victoria K; Smith Jr, Daniel L (2016) Nutrition and energetics in rodent longevity research. Exp Gerontol 86:90-96
Schwartz, Tonia S; Pearson, Phillip; Dawson, John et al. (2016) Effects of fluctuating temperature and food availability on reproduction and lifespan. Exp Gerontol 86:62-72
Razzoli, Maria; Bartolomucci, Alessandro (2016) The Dichotomous Effect of Chronic Stress on Obesity. Trends Endocrinol Metab 27:504-15
Jothery, Aqeel H Al; Vaanholt, Lobke M; Mody, Nimesh et al. (2016) Oxidative costs of reproduction in mouse strains selected for different levels of food intake and which differ in reproductive performance. Sci Rep 6:36353
Razzoli, Maria; Frontini, Andrea; Gurney, Allison et al. (2016) Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis. Mol Metab 5:19-33
Kunath, Nicolas; van Groen, Thomas; Allison, David B et al. (2015) Ghrelin agonist does not foster insulin resistance but improves cognition in an Alzheimer's disease mouse model. Sci Rep 5:11452

Showing the most recent 10 out of 17 publications