Abstract
Diet and sex are important determinants of lifespan. In humans, high sugar diets, obesity, and type 2 diabetes correlate with decreased lifespan, and females generally live longer than males. The nematode Caenorhabditis elegans is a classical model for aging studies, and has also proven useful for characterizing the response to high-glucose diets. However, studies on male animals are lacking. We found a surprising dichotomy: glucose regulates lifespan and aging in a sex-specific manner, with beneficial effects on males compared to toxic effects on hermaphrodites. High-glucose diet resulted in greater mobility with age for males, along with a modest increase in median lifespan. In contrast, high-glucose diets decrease both lifespan and mobility for hermaphrodites. Understanding sex-specific responses to high-glucose diets will be important for determining which evolutionarily conserved glucose-responsive pathways that regulate aging are "universal" and which are likely to be cell-type or sex-specific.
Highlights
Diet is a key regulator of lifespan: caloric intake, and in particular, glucose metabolism, must be tightly controlled for health and survival
We tested the effects of a high-glucose diet on two aging parameters in C. elegans: lifespan and mobility, which is an important measure of healthspan
Some of the effects of Dietary restriction (DR) in C. elegans are more pronounced in hermaphrodites compared to males, and DR differentially regulates several hundred genes between the sexes [22]
Summary
Diet is a key regulator of lifespan: caloric intake, and in particular, glucose metabolism, must be tightly controlled for health and survival. High levels of glucose lead to toxicity, which can manifest in humans as obesity and type 2 diabetes. These diseases, in turn, are correlated with decreased fertility and lifespan. Excess glucose leads to toxicity in C. elegans: high-glucose diets lead to decreased fertility and lifespan [3,4,5,6,7]. High-glucose diet leads to a reduction in functional capacity in C. elegans by several measures, including the locomotion response to touch [10], the ability to survive oxygen deprivation [11], the structural integrity of the nervous system [12], and pharyngeal pumping [4]. High-glucose diet reduces many of these healthspan parameters even in young adults, indicating that glucose affects ageassociated phenotypes long before differences in lifespan potential can be observed [4, 11, 12]
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