Genomic Instability and Epigenetic Changes during Aging

Abstract

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 revision 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. In conclusion, this review highlights the fundamental role that genomic instability plays in the aging process and underscores the need for continued research into these complex biological mechanisms.

Keywords: aging; chromatin; epigenetics; genomic instability; histones.

Figure 1

The hallmarks of aging and the central role of genomic instability. Indicated are the cellular and organismal functions, which are known to contribute to the aging process (adapted from López-Otín et al. [5]). Genomic instability is functionally interconnected with all other hallmarks because it comprises telomere length shortening, causes epigenetic alterations through the mutation of epigenetic modifiers or during the process of DNA repair, alters proteostasis via the increase in aberrant, mutated proteins, affects macro-autophagy via its involvement in the DNA repair process, leads to mitochondrial dysfunction via mutations in mitochondrial genomes, can trigger senescence upon DNA damage, is dependent on nutrient sensing pathways such as TOR for DNA repair, might alter intercellular communication through the impairment of the activation of the relevant signaling pathways, lowers the stem cell renewal potential via epigenetic alterations, triggers inflammation programs via DNA mutation and damage and might induce dysbiosis through the accumulation of genomic mutations in intestinal cells.