Examining the role of somatic mutations in aging gives insights into genome stability and repair

Researchers studied the accumulation of somatic mutations, due to genome repair and replication errors, their role in aging, and strategies to manage these mutations. The study was published on April 28 and was authored by Jan Vijg, Björn Schumacher, Abdulkadir Abakir, and several others.

The study, published in Trends in Molecular Medicine, delves into the complex nature of de novo somatic mutations and their implications for aging. The study states that somatic mutations, which vary from cell to cell, accumulate in virtually all tissues as individuals age. Reportedly, this accumulation is largely attributed to errors in DNA replication or repair. The research highlights that the evolutionary pressure to maintain genome sequence integrity predominantly focuses on the reproductive phase of life, leaving the post-reproductive phase less protected. Recent technological advancements in single-cell and high-depth sequencing have enabled a more detailed quantitative analysis of these mutations, the research states. This analysis reportedly not only aids in understanding the role of somatic mutations in aging but also explores the causal relationship between these mutations and the aging process.

According to the study, further insights reveal that the majority of somatic mutations do not lead to cancer, but rather contribute to the risk of both cancerous and non-cancerous age-related diseases, as well as overall mortality. The study underscores the inevitability of age-related somatic mutation accumulation, a phenomenon observed across a range of tissues in human bodies and model organisms. Although the full spectrum of mutation types and their characteristics is yet to be fully quantified, the initial findings indicate a significant increase in the somatic mutation burden with age. Additionally, the study states that a small fraction of these mutations undergo clonal expansion, providing a deeper understanding of their impact on cellular and organismal aging.

The study concludes with an exploration of potential interventions to mitigate the impact of somatic mutations. The researchers propose examining genome maintenance strategies from three perspectives: long-lived animals, species in high genotoxic environments, and the cellular maintenance observed in stem or germ cells. These strategies, according to the study, could potentially lead to clinical applications aimed at preventing or eliminating cells with high mutation burdens or enhancing somatic maintenance. Since aging is a major risk factor for chronic diseases in humans, the study argues that such interventions could significantly alter the human aging process, offering new avenues for extending healthspan and potentially modifying the rate of aging in our species.

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^{Elsevier Ltd: Jan Vijg, Björn Schumacher, et al., Mitigating age-related somatic mutation burden, Trends in Molecular Medicine (2023). DOI: https://doi.org/10.1016/j.molmed.2023.04.002}