An experiment in wild wood mice shows that supplementary feeding and treatment for intestinal parasites slow epigenetic clocks, which measure the rate of aging through chemical marks on DNA
An experiment in wild wood mice shows that supplementary feeding and treatment for intestinal parasites slow epigenetic clocks, which measure the rate of aging through chemical marks on DNA
A team from Edinburgh and the biotechnology company Altos Labs developed a DNA methylation clock for wood mice and applied it to a wild population near Edinburgh. The version dated 16 September describes a field experiment in which mice received both supplementary food and treatment for intestinal parasites. Their clocks ran significantly more slowly than those of untreated animals of the same chronological age.
The exact age of a wild animal is almost never known: animals are rarely captured at birth, and methods based on body mass, tooth wear or telomere length either provide only rough estimates or require the animal to be killed. Epigenetic clocks take a different approach. At specific sites in DNA, methylation, a chemical mark that influences gene activity, changes predictably with age. A set of these marks can therefore be used to predict age.
Sarah Wolf and her colleagues on the same team first trained the clock using 177 such marks in 74 laboratory wood mice of known age. Its age prediction error was 5,45 days in the training set and 14,64 days in an independent validation set. This is an order of magnitude more accurate than universal “pan-mammalian” clocks trained on 185 mammalian species. In the same laboratory mice, those clocks had errors of 152–175 days and sometimes overestimated age threefold, assigning ages of more than a thousand days, beyond the lifespan of a wood mouse.
Before relying on the clock in the field, the authors tested it on 273 samples from 163 wild mice captured in woodland near Edinburgh. In juveniles, predicted ages fell within an independently established age range. Across the sample, predicted age increased when the same animal was recaptured, declined over the breeding season as young animals entered the population, and was higher in mice with heavier mite infestations and viral infections.
The researchers chose these stressors for a specific reason: wild wood mice face both food shortages and intestinal parasites, and each factor has independently been associated with accelerated epigenetic aging in humans. Researchers cannot manipulate these exposures in humans, whereas short-lived mice can be assigned to experimental groups and recaptured within a few months.
The mice were randomly assigned to four groups, receiving either supplementary food or no supplementary food, and either an antiparasitic drug or water. Among the 101 mice captured twice, the clock advanced, on average, at almost the same rate as chronological time. In mice that received both food and the antiparasitic drug, however, the clock ran significantly more slowly than in the other groups. Because group assignment was random rather than based on health, the difference can be attributed to the intervention.
Two hypotheses could explain the mechanism. First, the additional energy from food may have supported tissue repair rather than growth and reproduction. Second, the effect was largely driven by mice that survived the winter in torpor. When a similar state was artificially induced in laboratory mice for nine consecutive months, it likewise slowed their blood epigenetic clocks by 37%.
Previous studies of epigenetic clocks in wild species generally went no further than showing agreement with expected age patterns. Here, supplementary feeding and treatment for intestinal parasites provided the first experimental demonstration in a wild mammal that an environmental intervention causally slows the rate of aging measured by an epigenetic clock. One co-author is Steve Horvath, who first described a human multi-tissue epigenetic clock in 2013, in a paper that has since been cited more than 7500 times. He is now a leading researcher at Altos Labs, a biotechnology company working on cellular rejuvenation.