DNA damage, which results in genomic instability, is one of the primary hallmarks of aging. Today, we want to highlight an recent open access review that explores the DNA damage response during aging.
The role of DNA damage
Some researchers have long suggested that damage to our DNA is a major reason why we age and a strong determinant of species longevity; indeed, many-long lived species have extremely stable genomes, such as bristlecone pines, which have lifespans of over 5000 years.
The naked mole rat lives for 30 years or more, making it a record holder for longevity among rodents. This is because it, like some other species, has very efficient DNA repair and therefore excellent genomic stability. It seems likely that the stability of the genome and the ability to repair its damage with minimal errors are substantial factors in the lifespan of a species.
Recently, researchers have shown evidence that DNA damage leads to epigenetic alterations, a process that causes cells to stop working properly and forget what cell types they are and appears to drive aging by causing disruption to metabolism. These epigenetic alterations are another hallmark of aging and are, at least in part, triggered by damage to the DNA and the resulting repair process, which causes gene expression to change over time as more double-strand breaks occur and are repaired. This is an intriguing development as it shows a direct causal link between genomic damage and changes in gene expression, both of which occur as we age.
In this new review, the researchers delve into the various mechanisms and evidence supporting the role of DNA damage in aging and is well worth reading to get a better understanding of the forces at play here.
Ageing appears to be a nearly universal feature of life, ranging from unicellular microorganisms to humans. Longevity depends on the maintenance of cellular functionality, and an organism’s ability to respond to stress has been linked to functional maintenance and longevity. Stress response pathways might indeed become therapeutic targets of therapies aimed at extending the healthy lifespan. Various progeroid syndromes have been linked to genome instability, indicating an important causal role of DNA damage accumulation in the ageing process and the development of age-related pathologies. Recently, non-cell-autonomous mechanisms including the systemic consequences of cellular senescence have been implicated in regulating organismal ageing. We discuss here the role of cellular and systemic mechanisms of ageing and their role in ageing-associated diseases.
Conclusion
It is becoming increasingly clear that DNA damage and the resulting epigenetic alterations that happen during aging are causes rather than consequences. As our understanding of these processes increases and our ability to reverse those changes is refined through partial cellular reprogramming, there is a real possibility that this particular hallmark could be mitigated, thus providing a potential treatment for the numerous diseases that have a genomic/epigenomic basis, including cancer, the poster child of age-related diseases.
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