Calorie Restriction Slows Epigenetic Changes Associated with Aging

The results noted here are unsurprising, a confirmation of what was expected by most in the field. The practice of calorie restriction has been shown to extend healthy life span and slow near all measures of aging in a range of species. Now that the research community has established a number of epigenetic clocks, characteristic patterns of DNA methylation that change in fairly predictable ways over the course of aging, it was only a matter of time before those too were shown to be slowed by calorie restriction. If, as is the consensus, calorie restriction does in fact slow the causes of aging, and slow aging as a process overall, then it should also slow all consequent measures of aging.

Where these publicity materials run awry is to paint epigenetic changes as a cause of aging. There is certainly a faction in the research community whose members consider aging to be a selected, evolved program, and place epigenetic changes as a root cause of aging. However I think they continue to have an uphill struggle to try to prove that case in the face of the overwhelming evidence for aging to be caused by accumulations of molecular damage, with epigenetic changes a downstream consequence of that damage: cells reacting to increased damage in the surrounding environment and themselves. The complexity of cellular biochemistry in a living individual means that this debate is unlikely be resolved through inspection before it is resolved by observing the results of different approaches to rejuvenation therapies. For example, clearance of senescent cells is a form of damage repair that extends life in mice: if that also turns back epigenetic changes of aging, something that has yet to be established in a published paper, then this would be strong evidence against epigenetic change as a cause of aging.

New research is the first to show that the speed at which the epigenome changes with age is associated with lifespan across species and that calorie restriction slows this process of change, potentially explaining its effects on longevity. "Our study shows that epigenetic drift, which is characterized by gains and losses in DNA methylation in the genome over time, occurs more rapidly in mice than in monkeys and more rapidly in monkeys than in humans." The findings help to explain why mice live only about two to three years on average, rhesus monkeys about 25 years, and humans 70 or 80 years.

Chemical modifications such as DNA methylation control mammalian genes, serving as bookmarks for when a gene should be used - a phenomenon known as epigenetics. Previous studies had shown that these changes occur with age, but whether they were also related to lifespan was unknown. The researchers made their discovery after first examining methylation patterns on DNA in blood collected from individuals of different ages for each of three species - mouse, monkey, and human. Mice ranged in age from a few months to almost three years, monkeys from less than one year to 30 years, and humans from age zero to 86 years (cord blood was used to represent age zero). Age-related variations in DNA methylation were analyzed by deep sequencing technology, which revealed distinct patterns, with gains in methylation in older individuals occurring at genomic sites that were unmethylated in young individuals, and vice versa.

In subsequent analyses, striking losses in gene expression were observed in genomic regions that had become increasingly methylated with age, whereas regions that had become less methylated showed increases in gene expression. Investigation of a subset of genes affected by age-related changes in methylation revealed an inverse relationship between methylation drift and longevity. In other words, the greater the amount of epigenetic change - and the more quickly it occurred - the shorter the species' lifespan.

One of the strongest factors known to increase lifespan in animals is calorie restriction, in which calories in the diet are reduced while still maintaining intake of essential nutrients. To examine its effects, the researchers cut calorie intake by 40 percent in young mice and by 30 percent in middle-aged monkeys. In both species, significant reductions in epigenetic drift were observed, such that age-related changes in methylation in old animals on the calorie-restricted diets were comparable to those of young animals. With the latest findings, the researchers were able to propose a new mechanism - the slowing of epigenetic drift - to explain how calorie restriction prolongs life in animals. "The impacts of calorie restriction on lifespan have been known for decades, but thanks to modern quantitative techniques, we are able to show for the first time a striking slowing down of epigenetic drift as lifespan increases."

Link: https://www.eurekalert.org/pub_releases/2017-09/tuhs-tru091317.php

Comments

Increased methylation with age, is this a fact? If methylation tags are wiped clean during the various genetic reboots early in development and even before in gametogenesis may make some sense that there is a gradual increase. However the idea of the full reboot, although still somewhat intact, has been upgraded to show that many epigenetic tags are preserved. Again, here is a good recent review on CR and epigenetics, unless this is getting comment purged too, https://medicalxpress.com/news/2017-09-caloric-restriction-anti-aging.html

Posted by: john hewitt at September 14th, 2017 8:29 AM

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