The Epigenetics of Calorie Restriction

The practice of calorie restriction slows aging, albeit to a much greater degree in short-lived mammals than is the case in our own species. Evidence suggests that upregulation of the cellular maintenance processes of autophagy are the primary mechanism by which calorie restriction produces its benefits to health and life span. Calorie restriction produces a major reshaping of all aspects of cellular behavior, however, a wide range of epigenetic changes that, along with autophagy, are the subject of the discussion in this open access paper.

Autophagy, such as a double-edged sword, can maintain cell survival and delay aging, but excessive autophagy can lead to cell death and promote aging. Therefore, how to precisely regulate and activate autophagy while clarifying the interaction between autophagy and epigenetic modifications may contribute to the proposal of anti-aging methods. Epigenetic modification, unlike DNA mutations, is a reversible regulation. CR prevents aging and aging-related diseases, in part through autophagy and reversing abnormal aging-related epigenetic alterations. This suggests that epigenetic modification is expected to be a potential therapeutic strategy against aging and its aging-related diseases. Further understanding of the role of epigenetics in human aging and longevity requires a deeper understanding of the influence of the external environment on epigenetics, such as the mechanism of epigenetics in CR-mediated longevity regulation.

Observational studies have shown that CR also has beneficial effects on human longevity. Among many well-known anti-aging strategies, CR has been identified as one of the effective interventions to combat the aging process and age-related pathological diseases (e.g., diabetes, kidney disease, cardiovascular disease, cancer, Alzheimer's disease, etc.). Thus, CR may influence the aging process by favorably affecting human health, and it is of considerable importance to be used to identify the underlying signaling mechanisms of aging. Mechanisms that extend lifespan through CR modulation of autophagic function or epigenetic modifications have also gradually been explored and focused. In this paper, we focus on autophagy and epigenetics to explore the molecular mechanism of caloric restriction delaying aging and its interactive relationship, providing a basis for the study of aging.


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