Ageing clocks accurately determine the biological age of humans with remarkable precision. Unlike chronological age, calculated from birth, biological age can be swayed by environmental influences like smoking or dietary habits. This precision suggests that ageing is not merely a linear process but follows a programmed pathway. Scientists David Meyer and Professor Dr Björn Schumacher from CECAD, the Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases at the University of Cologne, have uncovered that ageing clocks primarily measure the escalation of random or stochastic cellular changes. Their findings were detailed in the ‘Aging clocks based on accumulating stochastic variation’ study published in Nature Aging.
Professor Schumacher explains, “Aging is initiated by damage to the cellular building blocks, which mostly occurs randomly. Our research aligns the precision of aging clocks with the accumulation of stochastic alterations within our cells.”
As individuals age, the regulation of cellular processes declines, leading to increasingly stochastic outcomes. This is particularly noticeable in the stochastic changes observed in DNA methylation. Methylation involves chemical modifications that affect DNA, which are the fundamental components of the genome. While these methylation processes are usually tightly controlled, random variations in these patterns emerge over a person’s lifetime. The aggregation of these variations serves as an exact indicator of age.
The researchers, Meyer and Schumacher, have also shown that the increase in stochastic variations in gene activity could serve as a basis for an aging clock. Schumacher suggests, “Theoretically, it could be possible to extend this further, allowing stochastic variations in any cellular process to predict age.” He underscores the importance of determining whether such aging clocks can accurately reflect the effectiveness of age-slowing interventions or identify detrimental factors that accelerate aging. This could open up new avenues for the development of interventions that address the fundamental causes of ageing and potentially lead to cellular rejuvenation.
In their study, using existing datasets, the scientists illustrated that smoking amplifies these random human changes while ‘anti-ageing’ interventions, such as reduced calorie consumption in mice, decrease methylation pattern variations. They also discovered that this stochastic noise is reversible through cellular reprogramming to stem cells. The scientists compared human fibroblasts from the skin reprogrammed to stem cells, which showed rejuvenation due to the reprogramming, reversing the high variation typical of aged cells back to the low stochastic noise observed in young stem cells.
Meyer and Schumacher’s insights into the loss of regulation and the increase in stochastic variations could have significant implications. They could pave the way for new interventions that address the fundamental causes of ageing and potentially lead to cellular rejuvenation. For instance, potential targets for such interventions could include repairing stochastic changes in DNA or enhancing the control of gene expression. These interventions could slow the ageing process and improve health outcomes in ageing populations.
More information: David H. Meyer et al, Aging clocks based on accumulating stochastic variation, Nature Aging. DOI: 10.1038/s43587-024-00619-x
Journal information: Nature Aging Provided by University of Cologne
