24 December 2021

A watch for a digger

Gerontologists have learned to measure the biological age of naked diggers

Polina Loseva, N+1

American researchers have created an epigenetic clock that can be used to estimate the age of a naked digger. Thus, they found out that, at least at the cellular level, naked diggers age. Moreover, the queen of a colony that reproduces ages more slowly than non-reproducing workers. The work was published in the journal Nature Aging (Ruby et al., Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age).

A naked digger is sometimes called an animal that does not age — although no one is sure about this. On the one hand, it does not obey Gompertz's law, which applies to all aging species and according to which the risk of dying from natural causes increases over time. Naked diggers, unlike, for example, people, have not yet found such dependence. On the other hand, naked diggers have different age—related diseases - although much less often than other rodents. They were found to have tumors, kidney pathologies, and signs of decreased fertility. Therefore, the digger is not yet listed in the list of "negligibly aging" animals of the AnAge database.

To find out whether the digger is actually aging, a group of American gerontologists decided to look for signs of aging at the cellular level. The most accurate marker of biological age today is considered to be the epigenetic clock — a set of chemical labels on DNA, some of which appear with age, while others, on the contrary, disappear. Such watches for humans were built by Steve Horvath from the University of California in 2013, and since then they have been created for various other species. For example, with their help, scientists were able to compare the aging rate of humans and dogs.

Now Steve Horvath, together with his colleagues, undertook to build an epigenetic clock for a naked digger. To do this, they collected 382 DNA samples from different tissues in animals aged 0 to 26 years (the maximum known life expectancy in diggers is 37 years) and checked the presence or absence of epigenetic tags on 27917 genome sites. They built seven different clock models that allow predicting the age of a digger from a set of epigenetic markers. Four of them rely on data on individual tissues: skin, blood, liver and kidneys. The fifth watch allows you to use any available fabric sample from the digger. Finally, the researchers trained two more models on a mixed sample from the tissues of a digger and a human — and it turned out that all eight models allow us to accurately estimate the age of the diggers.

mole-rat1.jpg

The real (horizontal) and predicted (vertical) age of people (pink dots) and naked diggers (all other colors). Both models of watches are trained on a mixed sample of samples. Drawings from the article by Horvath et al.

Then the researchers tested their clocks on reprogrammed cells — these are the cells of adult diggers, which were artificially rejuvenated, turning into an analogue of embryonic cells (for more information about this method and its connection with aging therapy, see the article "Plans for old Age"). Their age turned out to be negative (on average -0.5 years) — which is expected, since these cells correspond to the embryonic stage of development of diggers, before birth.

Then the authors of the work tested their watches on diggers with different social statuses. Naked diggers are eusocial: only one female queen and a pair of males reproduce in their colony, and the rest of the individuals do not have a chance to reproduce unless someone from the "elite" dies. In other eusocial species (for example, Damarian sandworms, as well as ants and bees), representatives of the breeding caste live longer than all others. Therefore, the researchers compared the predictions of their epigenetic clocks for queens and ordinary female naked diggers. And in many cases, the real age of the queens turned out to be really lower than predicted — and the older they were, the stronger the spread turned out to be.

mole-rat2.jpg

The age of breeding (red) and non-breeding (black) individuals, real (horizontally) and predicted (vertically). F and M denote the sex of individuals. Queens (F red) often turn out to be younger than their non-reproducing peers

Thus, the authors of the work managed to find evidence that some aging processes are still going on in the cells of diggers. Nevertheless, the existence of all other aging processes in the digger will have to be proved separately — since it is known that epigenetic age does not always correlate with other biological clocks, for example, age calculated by the length of telomeres. And the researchers themselves do not claim in conclusion that they have received evidence of the aging of the diggers as a whole — only at the epigenetic level.

At the same time, the authors of the work note that naked diggers, apparently, somehow learned to separate epigenetic aging from physiological aging - that is, they acquired mechanisms that do not allow epigenetic changes to affect their health. And these mechanisms also have yet to be studied.

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