Aging occurs when the components of our cells are damaged. In most cases, this damage occurs randomly. The accuracy of these aging clocks suggests that the aging process follows a program.
Scientists David Meyer and Professor Björn Schumacher from CECAD, the University of Cologne’s cluster of excellence for cellular stress responses in aging-related diseases, have discovered that the aging clock measures increasing stochastic changes in cells.
For this study, scientists combined the precision of aging clocks with the accumulation of completely stochastic changes within cells.
As we age, our ability to regulate processes within our cells decreases, and outcomes become increasingly random. This is especially evident when looking at the accumulation of random variation in DNA methylation. Chemical changes that affect DNA, the basic unit of the genome, are called methylation. In the body, these methylation activities are tightly controlled. However, methylation patterns change randomly throughout life. Total variation is a very reliable way to calculate a person’s age.
DNA methylation is not the only factor contributing to loss of cellular control and increased stochastic variation. Scientists have shown that aging clocks can also be created by measuring increased stochastic fluctuations in gene activity.
Mr Schumacher said: “In principle, we could take this even further and use stochastic fluctuations in any process within a cell to predict age.” In particular, it will be important to see whether such aging clocks can indicate the success of interventions that slow the aging process or deleterious factors that accelerate aging.
Using available datasets, the scientists found that the variance in methylation patterns was reduced in mice subjected to “anti-aging” therapies such as caloric restriction, and that smoking promotes random changes in humans. was demonstrated. Furthermore, they demonstrated that stochastic noise is reversible by converting somatic cells into stem cells.
Reprogrammed human fibroblasts from the skin, which are rejuvenated cells, were compared to other human fibroblasts. The low stochastic noise of youthful stem cells was opposed to the significant variation indicating age of somatic cells.
This research is expected to lead to new interventions that may address the root causes of aging and even lead to cellular rejuvenation. Such interventions could target the repair of stochastic changes in DNA or improve control of gene expression.
Reference magazines:
- Meyer, DH, Schumacher, B. Clock aging based on accumulation of stochastic fluctuations. Nat Aging (2024). DOI: 10.1038/s43587-024-00619-x
