How do aging clocks tick?

Damage to our cells’ building blocks causes us to age. Most of the time, this injury happens randomly. The precision of these aging clocks suggests that the aging process follows a program.

Scientists David Meyer and Professor Dr Björn Schumacher at CECAD, the Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases of the University of Cologne, have discovered that aging clocks measure the increase in stochastic changes in cells.

For this work, scientists combined the accuracy of aging clocks with the accumulation of entirely stochastic changes in our cells.

As we age, our ability to regulate the processes in our cells diminishes, leading to increasingly random outcomes. This is especially clear when looking at the accumulation of random variations in DNA methylation. The chemical alterations that impact DNA, the fundamental unit of the genome, are referred to as methylation. Within the body, these methylation activities are tightly controlled. However, methylation patterns randomly alter during a person’s life. The total variation is a very reliable way to calculate someone’s age.

DNA methylation is not the only factor contributing to the loss of cell control and rise in stochastic variation. Scientists show that an aging clock can also be created by measuring the rise in stochastic variations in gene activity.

Schumacher said, “In principle, it would be feasible to take this even further, allowing the stochastic variations in any process in the cell to predict age.” Above all, it is crucial to ascertain whether such aging clocks can show the success of interventions that slow the aging process or harmful factors that accelerate aging.

By using the available datasets, scientists demonstrated that methylation pattern variance is reduced in mice that get ‘anti-aging’ therapies, such as calorie restriction, and that smoking promotes random changes in humans. Additionally, they demonstrated that the stochastic noise is reversible by converting body cells to stem cells.

The reprogrammed human fibroblasts from the skin, which are rejuvenating cells, were compared to other human fibroblasts. The low stochastic noise of youthful stem cells was the opposite of the significant variation that indicated the age of the body cells.

This study is expected to lead to new interventions that can tackle the root cause of aging and may even lead to cellular rejuvenation. Such interventions could target repairing stochastic changes in DNA or improved control of gene expression.

Journal Reference:

Meyer, D.H., Schumacher, B. Aging clocks based on accumulating stochastic variation. Nat Aging (2024). DOI: 10.1038/s43587-024-00619-x

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