A recent study reveals how aging in the amphibian axolotl is nearly completely halted.
In most animals, aging is marked by noticeable changes—such as a gradual decline in health and physiological function. But the axolotl (Ambystoma mexicanum), an amphibian in the salamander suborder, stands out as a rare exception.It likely experiences negligible senescence, a phenomenon where the aging process is significantly slowed or nearly absent.
The axolotl possesses a range of extraordinary traits associated with this slowed aging. Notably, it can regenerate damaged organs and tissues—including those in the eyes, lungs, and even the heart. It also demonstrates a heightened resistance to cancer and accumulates fewer senescent cells over its lifespan. Senescent cells, which stop dividing but don’t die, are a hallmark of aging and contribute to age-related diseases. In captivity, axolotls typically live between 10 and 13 years, making them a valuable model for studying their aging processes. A recent, yet-to-be peer-reviewed study, offers new insights into the molecular mechanisms underlying the axolotl’s slowed aging.
At the molecular level, one of the most prominent markers of aging is the accumulation of DNA methylation. This process involves the addition of a methyl group (CH₃) to DNA without altering its underlying sequence. These changes—known as epigenetic modifications—can either suppress or activate the expression of specific genes.Methylation does not occur randomly along the DNA strand. It most often happens at sites where the nitrogenous bases cytosine (C) and guanine (G)—two of the building blocks of DNA—appear together. These sites are known as CpG sites or cytosine-guanine (CG) dinucleotide sites. These CG pairs can occur in long stretches, and as an organism ages, they tend to become increasingly methylated. The overall level of methylation, referred to as the epigenetic clock, can be used to estimate a cell’s biological age.
According to epigenetic clocks, the axolotl ages only during its first four years. Axolotl in an aquarium | rsaggin, Shutterstock
The Battery That Just Keeps Going
Researchers examined DNA methylation changes in axolotl tissues throughout their lifespan, analyzing samples from the tail, skin, liver, and other organs in individuals aged from four weeks to 21 years. They found that, unlike in mammals, methylation levels in axolotls remained remarkably stable. According to the axolotl’s epigenetic clocks, aging occurs only during the first four years of life—after which its aging appears to halt, with no molecular changes in the tissues associated with aging. Researcher Maximina H. Yun suggests this may be evidence of negligible aging in axolotls—at least at the epigenetic level. She adds that it’s still unclear what actually causes the death of axolotls.
The methylation patterns observed during the first third of the axolotl’s life closely resemble those found in frogs and humans, suggesting that common biological mechanisms underlie aging across different species. While the axolotl’s later-life epigenetic patterns differ from typical aging processes, these molecular changes alone are insufficient to conclusively classify its aging as negligible. Researcher João Pedro de Magalhães of the University of Birmingham, who was not involved in the study, emphasizes the need to evaluate the axolotl’s physical traits and abilities alongside its epigenetic changes to fully understand its aging process. While further research is required, this study offers valuable molecular insights into negligible senescence and advances our understanding of aging dynamics across animals.