June 2023
3.2. Epigenetic diet
"...Giving up smoking and alcohol are effective in decreasing accelerated biological aging. However, those lifestyle interventions are by far insufficient for longevity medicine practice. Studies on the dietary factors affecting epigenetic aging have a wider reach and can be used to discover potential geroprotectors.
The most well-known dietary intervention with a proven effect on epigenetics is caloric restriction (CR). A prolonged up-to-40% reduction in calorie intake has been shown to prevent age-related methylome changes in model organisms(Gensous et al., 2019). Even a short-term (four weeks) CR remodels the DNAm profiles of genes involved in diabetes, inflammation, and cardiovascular health-related pathways in old rats(Kim et al., 2016). Similar results have been obtained with rhesus monkeys; long-term CR delayed the onset of age-associated pathologies and greatly improved the survival rate (Colman et al., 2009). In the CR cohort, 20% of the monkeys died from age-related causes by the age of 30, while 50% died in the control cohort. After adjusting for the lifespan difference between species, a similar drop in mortality for humans would be observed at the age of 91 years(Tacutu et al., 2018).
Until recently, the efficiency of CR in humans had not been measured, although some attempts were made to extrapolate the results obtained in primate studies(Maegawa et al., 2017). A2021 human study of CR involved 43 older adult males who underwent an eight-week program combining CR with exercise, dietary supplements, and guidance(Fitzgerald et al., 2021). The regimen resulted in an epigenetic age decrease of 2–3 years, as measured by the 2013 Horvath’s clock. In the 2023 CALERIE study, 128 people had their caloric intake reduced by 25% and observed for two years (Waziry et al., 2023). A slight yet statistically reliable change in the pace of aging, as measured with DunedinPACE, was observed in a dose-dependent manner in response to CR. The other two aging clocks used in the study (GrimAge, PhenoAge) were unable to detect any aging-related changes in the CR group. The 2–3% deceleration of aging detected in CALERIE was interpreted by the authors as a 10–15% reduction in mortality rate.
Some other non-CR diets have also been assessed for their ability to decelerate epigenetic aging. In an exploration of epigenetic age in 2694 adult women, their pace of aging was put in the context of adherence to four dietary indices: DASH, HEI, aHEI, aMED (Kresovich et al., 2022). These indices represent the healthiness of a diet by assigning points based on diet composition with higher scores obtained by people who consume more vegetables, fruits, protein, polyunsaturated and omega-3 fatty acids, and those who consume less alcohol, sugars, and sweetened foods (Chiuve et al., 2012, Fung et al., 2009, Fung et al., 2008, Krebs-Smith et al., 2018). While four epigenetic clocks were tested in the study, only two (PhenoAge and GrimAge) showed significant associations with diet index adherence. Interestingly, even in these two clocks the beneficial effect of healthy eating was higher in people with low levels of physical activity. For example, women with dietary scores in the upper quartile are 0.8–1.5 years younger compared to the lower quartile, based on PhenoAge estimates. In women with more than 2.5 h of weekly activity, however, this aging decelerating is not observed at all. The authors hypothesize that diet and exercise act on the same epigenetic pathways reflected in PhenoAge and thus their effects do not stack.
Although in (Kresovich et al., 2022) Horvath’s (2013) clock did not detect a significant effect of diet quality on the aging rate, a more recent study has displayed its utility in a longitudinal setting. In (Fitzgerald et al., 2023), six people underwent an eight-week “methylation-supportive diet and lifestyle program” which involved breathing exercises, physical training, dietary and supplement prescriptions, and intermittent fasting. At the end of observation, the epigenetic age of the participants was reduced by 4.60 years on average (0.0–11.0 years range). In another recent study featuring a custom clock using only 70 CpG sites from six genes, one year of epigenetic diet resulted in a 0.58 year decrease in epigenetic age (Gensous et al., 2022). Compared to cross-sectional or retrospective studies, such designs allow us to assess the efficiency of anti-aging diets and other interventions in realistic settings and measure adherence.
A study of eating habits conducted on 407 subjects showed that the consumption of fish and poultry significantly decreased the pace of aging(Quach et al., 2017). Similarly, a diet rich in fruits and vegetables, as indicated by high blood carotenoids, has also been associated with aging deceleration(Quach et al., 2017). However, due to the methodology of the study, the effect of these factors cannot be translated into a specific number of years. Similar results were obtained in another recent study conducted on 219 women who followed a two-year plant-based diet plan(Fiorito et al., 2021). The participants in the intervention arm were, on average, 0.41 years younger than their chronological age at the end of observation, although this effect may have been confounded by the increased physical activity in which some were required to engage.
Some individual compounds (polyphenols in particular) have recently gained a lot of attention from the anti-aging community due to their effects on the epigenome mediated by their interactions with DNMTs, histone modifiers, and miRNAs (Abdul et al., 2017). There are also strong indications that curcumin, a major component of curry spice, may promote favorable epigenetic changes(Benameur et al., 2021; Reuter et al., 2011). Other plant polyphenols, such as quercetin and pterostilbene, have also been associated with epigenetic remodeling(Arora et al., 2020; Busch et al., 2015). However, the effect of these compounds on DNMTs has not been quantified in the context of aging. Thus, the concept of an epigenetic rejuvenation diet is still rather vaguely understood.
The positive effect of polyphenols is considered to be partially caused by their interactions with sirtuins, a group of proteins involved in DNA repair, circadian rhythms, and stress response. In particular, SIRT1 is involved in cellular senescence and prevents telomere attrition(Arora et al., 2020). The green tea polyphenol epigallocatechin-3-gallate (EGCG) has been shown to attenuate systemic inflammation and extend rat lifespan by 8–12 weeks(Niu et al., 2013). Another common polyphenol, resveratrol—shown to inhibit senescence and boost SIRT1 expression—is found in berries, grapes, and peanuts. Finally, genistein, which naturally occurs in soybeans, is known to directly inhibit DNMT1, DNMT3A, and DNMT3A, and consequently affect the global methylation pattern.
Although some reports suggest that other foods, such as garlic, Brazil nuts, parsley, and coffee, can affect epigenetic aging, the epigenetics of nutrition at large remains an underexplored field(Lea et al., 2001; Xiang et al., 2008). In most cases, the rejuvenative potential of specific ingredients or diets has not been properly measured due to a large number of confounders. Hopefully, the widespread use of consumer epigenetic screening will bring more clarity regarding this matter...."
Stress, diet, exercise: Common environmental factors and their impact on epigenetic age. Ageing Research Reviews. 2023;88:101956.
https://www.scienced...568163723001150
