DNA Repair and Cellular Processes

**163**

**Chapter 8**

**Abstract**

associated.

**1. Introduction**

The Role of DNA Repair in

Aging is defined as the time-dependent decline of functional properties. One common denominator of aging is mitochondrial dysfunction and accumulation of genetic damage throughout life. In fact, the imperfect maintenance of nuclear and mitochondrial DNA likely represents a critical contributor of aging. Each day, the integrity and stability of DNA are challenged by exogenous physical, chemical, or biological agents, as well as by endogenous processes, including DNA replication mistakes, spontaneous hydrolytic reactions, and reactive oxygen species. In this way, DNA repair systems have evolved a complex network that is collectively able of dealing with most of the damages inflicted. However, their efficiency may decrease with age and, therefore, influence the rate of aging. Thus, the purpose of this work is to summarize the recent knowledge in cellular aging process and its link with DNA repair systems, with a particular emphasis on the molecular mechanisms

Aging is a complex biological process that results in a progressive loss of physi-

ological integrity. Overall, aging is a consequence of accumulation of cellular damage and is characterized by nine hallmarks: genomic instability, telomere attrition, epigenetic alterations, cellular senescence, mitochondrial dysfunction, loss of proteostasis, deregulated nutrient sensing, stem cell exhaustion, and altered intercellular communication (**Figure 1**) [1]. Although aging may involve damage to various cellular constituents, there is evidence suggesting that DNA constitutes the key target in this process [2]; consequently, genomic instability is the main factor of aging [3–5]. Genome instability has been implicated as a cause of aging since unrepaired DNA damage, DNA mutations, and epimutations accumulate in an age-related manner [3]. In the same way, the notion that multi-system premature aging syndromes are mainly caused by defects in genome maintenance or affect genome function highlights the role of genome integrity in aging [6]. Meanwhile, normal aging is accompanied by telomere shortening with cell division due to the "end-replication problem" and telomere end processing. Currently, there is a wide body of evidence associating reduction in the length of telomeres with failure of cell division and senescence of normal cells, and oxidative stress and inflammation can contribute to the rate of attrition of telomere length [7]. Age-related changes involve

**Keywords:** DNA damage, DNA repair, BER, NER, MMR, HR, NHEJ

Cellular Aging Process

*Francisco Alejandro Lagunas-Rangel* 

*and Rosa María Bermúdez-Cruz*
