Genomic Instability |
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Hallmarks of Aging Miniseries No. 1 Genomic Instability
As cells age, chromosomes lose their stability. Genomic instability is a key hallmark of aging.
Although there is much evidence linking genomic and epigenomic changes to disorders involving accelerated aging, it’s been trickier to relate these changes to natural aging. Of all the DNA lesions that occur as a result of endogenous and environmental insults, it’s clear that some (like retrotransposon movement and large chromosomal rearrangements) contribute more than others.
Underlying all the manifestations of genomic instability is compromised DNA repair. Indeed, today’s aging research focuses on age-related changes in activation of key DNA repair pathways, involving p53, ATM, histone H2A.X, XRCC4 and ligase 4. What environmental factors can hinder DNA repair? Evidence points to general physiological stress (exacerbated by behaviors like chronic alcohol consumption) and disrupted circadian rhythm. That’s right – don’t stay up all night, so your genome can recover from daytime damage!
Of course, it’s also possible that decreased DNA repair is itself a symptom, not a cause, of aging. To investigate this possibility, researchers will need to examine changes in transcriptional regulators of repair genes, such as ncRNAs, hormones, and other chromatin modulators.
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