The diggers are still getting old
Naked digger caught aging at the cellular level
Daria Spasskaya, N+1
Researchers have found several types of cellular aging in the naked digger (Heterocephalus glaber) due to the embryonic development program or stress effects, according to an article in the Proceedings of the National Academy of Sciences (Zhao et al., Naked mole rats can undergo developmental, oncogene-induced and DNA damage-induced cellular senescence). Thus, the unique lifespan and "eternally young" phenotype of these animals is not determined by the absence of cellular aging.
Cellular aging (a process that in English terminology is referred to as senescence – in contrast to aging, which means the aging of the whole organism) is primarily determined by the irreversible blocking of the cell cycle after a series of divisions. This process is generally accompanied by a decrease in the level of metabolism and energy exchange.
Cellular aging can occur as a result of the cell reaching the Hayflick limit, which implies the ability to share only a certain number of times (replicative aging), or as a result of stress, for example, DNA damage or activation of oncogenes. The mechanisms of "aging" are also activated in tissues during embryonic development.
Thus, this process is natural for all organisms, and in the course of evolution appeared, probably, to fight cancer. Nevertheless, it contributes to the overall aging of the organism (aging) – with age in multicellular organisms, the percentage of "aged" cells increases. In experiments, the artificial removal of such cells prolonged the life of mice.
Researchers from the University of Rochester, led by Vera Gorbunova and Andrey Seluyanov, in collaboration with the Skolkovo Institute of Science and Technology in Moscow, tested the presence of three types of cellular aging in a naked digger: oncogen-induced, induced by DNA damage associated with embryonic development.
These mammals are known for a unique rodent lifespan (about 30 years), they are not subject to the law of mortality Gompertz, they are characterized by almost complete absence of signs of aging at the body level and high resistance to the formation of tumors. Previously, researchers have shown that naked diggers are not characterized by replicative aging of cells, and their resistance to cancer is due to other mechanisms (for example, the presence of a special hybrid protein-a tumor suppressor that causes the arrest of the cell cycle, which in this context can also be called cellular aging). In a new paper, scientists have found that all other types of cellular aging in these animals work.
The presence of "embryonic aging" in animals was confirmed by the color of the cells of the nail plate, dermis of the skin and hair follicles for the presence of a marker of cellular aging – beta-galactosidase. The transformation of primary skin fibroblasts and embryonic cells by oncogenic Ras protein also led to the accumulation of galactosidase in cells and the stopping of DNA synthesis, both in naked diggers and in control mice.
In the next experiment, mouse and digger fibroblasts were exposed to DNA-damaging gamma radiation. Cells of both species demonstrated cell cycle arrest and accumulation of aging markers, however, if a dose of 10 gray was enough for mouse cells, a twice as large dose was needed for digger cells. Despite the same level of DNA damage, the digger cells refused to go into apoptosis, to commit programmed cell suicide induced by significant DNA damage.
According to the authors, in order to assess the contribution of cellular aging to the aging of the body in naked diggers, it is necessary to calculate the number of senescent ("aged") cells in the body of an old animal (in old mice, for example, their number is about 17 percent). However, since diggers live too long, it is quite difficult to find a sufficient number of old individuals for statistics, so scientists have not done this yet.
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