Better Living through Chemistry: Caloric Restriction (CR) and CR Mimetics Alter Genome Function to Promote Increased Health and Lifespan

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.

Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism

“…However, the precise mechanisms mediating the effects of DR remain elusive [1, 5, 6, 16] and are likely to be time-dependent [16, 17]. DR induces major and tissue-specific changes in gene expression [18–20], and these have implicated shifts in energy homeostasis, mitochondrial function and lipid metabolism [16, 17, 21–23] as important processes induced by DR to improve health during ageing. Lipid and fatty acid metabolism are emerging as particularly central candidates, as these were commonly identified in two large-scale meta-analyses of more than 30 transcriptome datasets of independent DR experiments and originating from various tissues [18, 19].…”

Aging, Calorie Restriction and Calorie Restriction Mimetics

“…Interventions for the purpose of healthy aging and longevity should include the attenuation or deceleration of some, if not all, already mentioned molecular-cellular changes, which include the aging process, the processes of inducing pathology associated with aging, and in particular, processes of deregulated sensing of nutrients or energy 1 . It has been shown that various interventions, including genetic manipulation, some drugs implementation and calorie limitation, extend the lifespan of several experimental models 11 . The superiority of some of these strategies in extending life expectancy has not been known until recently.…”

Non-genetic Transgenerational Inheritance of Acquired Traits in Drosophila

“…Recent work has demonstrated that many factors, including environmental conditions (e.g., diet) and genetic mutations, can impact the aging process across species [61][62][63]. In particular, anti-aging interventions often delay or prevent multiple ARDs in animal models [62][63][64], stimulating the emerging interdisciplinary field of geroscience to study the connection between aging and diseases, and to develop novel multi-disease preventative and therapeutic interventions by targeting the aging process itself [59,65]. There are clear practical and ethical complications associated with studying aging and its transgenerational inheritance directly in human populations.…”