New research shows that stochastic variation alone could create aging clocks that correlate with actual biological age.
We all witness aging in different ways – the fraying threads of muscle and memory that come undone as time passes. But not everyone ages in a similar fashion, and while some aging is due to the body’s reduced capacity for repair, some is due to an accumulation of unpredictable, stochastic damages.
Stochastic damage can be due to factors like oxidative stress, environmental exposures and other age-related biological processes, and these “frayed threads” gradually unravel cellular structures, raising susceptibility to age-related conditions such as cardiovascular disease, diabetes and neurological disorders
Researchers have come up with aging clocks in recent years that provide information on the biological age of organisms. One of the first aging clocks, developed in 2011, was based on cytosine phosphate guanine (CpG) islands which indicate different aspects of health [1]. Continuing development of aging clocks have sparked the question: Is aging merely a result of stochastic (random) events?
Longevity.Technology: Epigenetic drift may sound like a progressive rock concept album from the Seventies, but it refers to the gradual and often age-related changes in DNA methylation patterns that occur over time. Often caused by the imperfect preservation of epigenetic markers over time, this drift can lead to a loss of distinct methylation patterns between genomic regions, which were initially established during early development. Such changes can affect gene expression and are thought to contribute to aging and age-related diseases.
Epigenetic clocks, therefore, seek to map these changes, predicting how close a biological system might be to aging milestones. Across species, epigenetic drift is consistent, with about 30% of the mouse genome showing age-linked epigenetic alterations – a promising foundation for building biological clocks.
A new study published in Nature Aging aimed to determine whether stochastic changes alone can create aging clocks. Interestingly, researchers discovered that even minor variations in this random damage were capable of accurately predicting age-related changes. Stochastic variation was sufficient to estimate age across different species, such as the worm C elegans, with considerable accuracy (correlating with the biological age of 993 independent C elegans RNA-seq samples) [2].
While an increase in stochastic variation was observed to accelerate the aging process, this study also demonstrated that aging clocks could estimate the effects of therapeutic interventions aimed at slowing biological aging. It was shown that a slight reduction in stochastic variation – akin to halting the fraying of those cellular threads – could decelerate predicted aging rates [2]. The stochastic transcriptomic data-based clock predictions of C elegans could also predict the chronological age as well as the deceleration of biological age due to a pharmacological intervention – good news for tracking effectiveness of therapies.
By manipulating DNA methylation data, scientists found that stochastic models accurately mirrored biological age, even across diverse tissues and experimental platforms. It was also reported that even high maintenance rates could give accurate age predictions and that simulating epigenetic stochastic data starting from a young biological sample could also produce predictions that are correlated with the chronological age of independent biological samples. Finally, the stochastic data-based clock was also found to identify tissue and platform-independent signatures of age, thereby accurately predicting biological age [2].
The research suggests that stochastic variation accumulation can serve as a potent measure of both biological and chronological age. These aging clocks, based on random damage, may have significant implications for aging therapies, as well as being able to provide insights into how aging could be driven by entropy and randomness rather than a predetermined aging program.. By reducing the random wear-and-tear at a molecular level, future treatments could not only slow aging but potentially enhance the quality of life. These findings demonstrate the power of biological aging clocks and reinforce the notion that while aging may well be inevitable, its speed – and perhaps even its impact – can be modulated.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245174/
[2] https://www.nature.com/articles/s43587-024-00619-x
