Age-Related DNA Damage and Epigenetic Changes

This review paper covers both genetic and epigenetic changes that occur with age, taking a broad look at everything from telomere length to stochastic mutational damage to alterations in chromatin structure. As for all aspects of aging at the level of cellular biochemistry, it is easier to catalog than it is to determine relationships between these items, or to determine whether one characteristic of aging cellular biochemistry is more or less important than another when it comes to age-related disease and loss of function. Greater funding for the field would allow researchers to take the best of brute force approaches, which is to find ways to reverse each specific form of change observed in cells, and then compare the results. This is also the most likely way forward to discovering novel rejuvenation therapies.

Aging is considered the deterioration of physiological functions along with an increased mortality rate. This scientific review focuses on the central importance of genomic instability during the aging process, encompassing a range of cellular and molecular changes that occur with advancing age. In particular, this review addresses the genetic and epigenetic alterations that contribute to genomic instability, such as telomere shortening, DNA damage accumulation, and decreased DNA repair capacity. Furthermore, the review explores the epigenetic changes that occur with aging, including modifications to histones, DNA methylation patterns, and the role of non-coding RNAs. Finally, the review discusses the organization of chromatin and its contribution to genomic instability, including heterochromatin loss, chromatin remodeling, and changes in nucleosome and histone abundance.

The simultaneous occurrence of these alterations, each with its activating or inhibiting role, affects DNA availability and contributes to genomic instability, overall decline in cellular function, and organismal dysregulation. Consequently, there is an increased susceptibility to age-related diseases such as cancer, cardiovascular diseases, and inflammation. Since the initial suggestion that DNA damage and genome instability are primary drivers and DNA repair is a key factor in aging, followed by the finding that defects in DNA repair can hasten the progression of various age-related diseases, significant progress has been made in understanding the detailed connections between genome instability and every facet of the aging process. Exploring the specific mechanisms by which DNA damage impacts each major process contributing to age-related diseases offers promising avenues to address aging at its fundamental causes, thereby mitigating diseases associated with aging.