Epigenetic Regulation of Metabolism and Inflammation by Calorie Restriction

Abstract

Chronic caloric restriction (CR) without malnutrition is known to affect different cellular processes such as stem cell function, cell senescence, inflammation, and metabolism. Despite the differences in the implementation of CR, the reduction of calories produces a widespread beneficial effect in noncommunicable chronic diseases, which can be explained by improvements in immuno-metabolic adaptation. Cellular adaptation that occurs in response to dietary patterns can be explained by alterations in epigenetic mechanisms such as DNA methylation, histone modifications, and microRNA. In this review, we define these modifications and systematically summarize the current evidence related to CR and the epigenome. We then explain the significance of genome-wide epigenetic modifications in the context of disease development. Although substantial evidence exists for the widespread effect of CR on longevity, there is no consensus regarding the epigenetic regulations of the underlying cellular mechanisms that lead to improved health. We provide compelling evidence that CR produces long-lasting epigenetic effects that mediate expression of genes related to immuno-metabolic processes. Epigenetic reprogramming of the underlying chronic low-grade inflammation by CR can lead to immunometabolic adaptations that enhance quality of life, extend lifespan, and delay chronic disease onset.

Epigenetic signatures underlying inflammation: an interplay of nutrition, physical activity, metabolic diseases, and environmental factors for personalized nutrition

“…Further, increasing research has provided evidence about the long-lasting epigenetic effects of calorie restriction which mediates expression of genes related to immuno-metabolic processes that may enhance quality of life and extend lifespan, with important applications for the prevention of chronic inflammatory diseases [47]. Interestingly, methylation profiles in inflammatory genes have been proposed to be used as epigenetic biomarkers concerning adiposity and metabolic outcomes in response to low-calorie diets (30% of energy restriction, 55% of energy as carbohydrates, 15% as proteins, and 30% as lipids) [48,49].…”

Epigenetic contribution to obesity

“…Interestingly, the methylation patterns of ATP10A, AQP9, CD44 DUSP22, HIPK3, TNNT1 , and TNNI3 could be used as early indicators of the intervention success, indicating that the interindividual variability of the epigenetic background plays a role on the effectiveness of a weight management program (Milagro et al 2011 ; Moleres et al 2013 ). Another short-term caloric restriction in overweight women was shown to decrease methylation of CD36, CD14, PDK4 , and FADS1 in PBMCs (do Amaral et al 2014 ; Hernandez-Saavedra et al 2019 ). A long-term caloric restriction (6 months) with a 4-week weight maintenance period resulted in more than 3% reduction of body fat and in hypermethylation of PLCH2 and PRDM8 in SAT biopsies (Bouchard et al 2010 ) (Fig.…”

Maternal Exposure to High-Fat Diet Induces Long-Term Derepressive Chromatin Marks in the Heart

“…In addition, DNA demethylation can take place in a passive mode passively through the loss of DNA methylation activity, or actively through "reverse" enzymatic reaction driven by DNA methyltransferases in the absence of S-adenosyl-methionine, methyl CpG binding (MBD) proteins and the Ten-Eleven-Translocation (TET) family of enzymes [45,46]. Certain interventions such as caloric restriction [47], chemical drugs [48], and dietary supplementation [49] can reverse the inappropriate changes in chromatin. In the case of nutrients, levels of S-adenosylmethione and S-adenosylhomocysteine, which are substrates involved in DNA methylation, can be regulated through folate, vitamins B6 and B12, riboflavin, methionine, choline and betaine.…”