Journal Article

Macronutrient balance, reproductive function, and lifespan in aging mice

Walters, Kirsty A., McMahon, Aisling C., Ballard, John William O., Handelsman, David J., Solon-Biet, Samantha M., Simanainen, Ulla K., Le Couteur, David G., Simpson, Stephen J., Ruohonen, Kari, Raubenheimer, David

2015

Overview

Significance A fundamental tenet of life-history theory is that reproduction and longevity trade off against one another. Experiments on invertebrates show that, rather than competing for limiting resources, reproduction and lifespan are optimized on different dietary macronutrient compositions. In mice, studies have yet to establish the relationship between macronutrient balance, reproduction, and lifespan. We evaluated the effects of macronutrients and energy on lifespan and reproductive function. Indicators of reproductive function (uterine mass, ovarian follicle number, testes mass, epididymal sperm counts) were optimized by high protein (P), low carbohydrate (C) diets whereas lifespan was greatest on low P:C diets. Corpora lutea and estrous cycling were higher in females on lower P:C diets. Macronutrient balance has profound and opposing effects on reproduction and longevity. In invertebrates, reproductive output and lifespan are profoundly impacted by dietary macronutrient balance, with these traits achieving their maxima on different diet compositions, giving the appearance of a resource-based tradeoff between reproduction and longevity. For the first time in a mammal, to our knowledge, we evaluate the effects of dietary protein (P), carbohydrate (C), fat (F), and energy (E) on lifespan and reproductive function in aging male and female mice. We show that, as in invertebrates, the balance of macronutrients has marked and largely opposing effects on reproductive and longevity outcomes. Mice were provided ad libitum access to one of 25 diets differing in P, C, F, and E content, with reproductive outcomes assessed at 15 months. An optimal balance of macronutrients exists for reproductive function, which, for most measures, differs from the diets that optimize lifespan, and this response differs with sex. Maximal longevity was achieved on diets containing a P:C ratio of 1:13 in males and 1:11 for females. Diets that optimized testes mass and epididymal sperm counts (indicators of gamete production) contained a higher P:C ratio (1:1) than those that maximized lifespan. In females, uterine mass (an indicator of estrogenic activity) was also greatest on high P:C diets (1:1) whereas ovarian follicle number was greatest on P:C 3:1 associated with high-F intakes. By contrast, estrous cycling was more likely in mice on lower P:C (1:8), and the number of corpora lutea, indicative of recent ovulations, was greatest on P:C similar to those supporting greatest longevity (1:11).

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Aging / Aging - drug effects / Aging - physiology / Animal reproduction / Animals / Biological Sciences / corpus luteum / Diet / Dietary Carbohydrates - pharmacology / Dietary Fats - pharmacology / Dietary minerals / Dietary Proteins - pharmacology / energy / Estrous Cycle - drug effects / Female / Females / Germ Cells - cytology / Germ Cells - drug effects / Invertebrates / Life expectancy / life history / Life span / Longevity / Longevity - drug effects / Longevity - physiology / Male / mice / Mice, Inbred C57BL / ovarian follicles / Ovary - cytology / Ovary - drug effects / reproduction / Reproduction - drug effects / Reproduction - physiology / Rodents / spermatozoa / testes