Abstract
Caloric restriction (CR), defined as decreased nutrient intake without causing malnutrition, has been documented to increase both health and lifespan across numerous organisms, including humans. Many drugs and other compounds naturally occurring in our diet (nutraceuticals) have been postulated to act as mimetics of caloric restriction, leading to a wave of research investigating the efficacy of these compounds in preventing age-related diseases and promoting healthier, longer lifespans. Although well studied at the biochemical level, there are still many unanswered questions about how CR and CR mimetics impact genome function and structure. Here we discuss how genome function and structure are influenced by CR and potential CR mimetics, including changes in gene expression profiles and epigenetic modifications and their potential to identify the genetic fountain of youth.
Highlights
The aging process is undoubtedly the single most significant contributor to disease and death
Knockout of FOXO3a in mice demonstrated that they no longer benefit from caloric restriction (CR), indicating that this transcription factor is central in regulating genes that promote increased health and lifespan (Shimokawa et al, 2015), possibly mediating the interaction and functions of Sirtuin 1 (SIRT1) and p53
An examination of 98 xenobiotic processing genes demonstrated an increase in expression of these genes, and that CR favored the expression of female pre-dominantly expressed genes over predominantly male expressed detoxification genes in the livers of male mice. These findings indicate that the CR may be inducing a shift toward maintenance and repair and re-establishing the expression of genes involved with detoxification, supporting the hormesis model
Summary
The aging process is undoubtedly the single most significant contributor to disease and death. Several lines of research indicate that certain behaviors can increase our health and potentially lifespan, such as exercise and regimes to improve cardiovascular function. One such intervention is the use of dietary/caloric restriction (CR); the reduced intake of calories/nutrients without causing malnutrition. This observation has been verified across a large number of model organisms (Longo, 2009; Lee and Longo, 2016) These observations demonstrated an increase in the lifespan, and in healthspan (time spent being healthy) of these organisms coincident with a significant decrease in age-related pathologies such as cardiovascular disease, diabetes and a number of cancers. We will discuss the effect of CR on genome function and structure and compare the impact of CR mimetics in an attempt to gage their ability to increase health and lifespan at the genetic level
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