The Role of DNA Repair in Cellular Aging Process

Lagunas‐Rangel, Francisco Alejandro; Bermúdez‐Cruz, Rosa María

doi:10.5772/intechopen.84628

Cited by 11 publications

(11 citation statements)

References 88 publications

(95 reference statements)

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“…Currently, there are many theories that give their explanation of the causes of aging, but there is no unanimous opinion on the problem [12,13,14]. We share the viewpoint that in the case of a multicultural organism, aging is always accompanied by a decrease in the resources required by its cells for repair and tissue regeneration [15,16,17,18]. The reasons for such a decrease in resources are well explained in our theoretical model of the functional division of the metazoan genome [19,20].…”

Section: Introductionmentioning

confidence: 77%

DNA methylation meta-analysis confirms the division of the genome into two functional groups

Salnikov¹,

Goldberg

Sukumaran

et al. 2022

Preprint

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Based on a meta-analysis of human genome methylation data, we tested a theoretical model in which aging is explained by the redistribution of limited resources in cells between two main tasks of the organism: its self-sustenance based on the function of the housekeeping gene group (HG) and functional differentiation, provided by the (IntG) integrative gene group. A meta-analysis of methylation of 100 genes, 50 in the HG group and 50 in IntG, showed significant differences ( p<0.0001) between our groups in the level of absolute methylation values of genes bodies and its promoters. We showed a reliable decrease of absolute methylation values in IntG with rising age in contrast to HG, where this level remained constant. The one-sided decrease in methylation in the IntG group is indirectly confirmed by the dispersion data analysis, which also decreased in the genes of this group. The imbalance between HG and IntG in methylation levels suggests that this IntG-shift is a side effect of the ontogenesis grownup program and the main cause of aging. The theoretical model of functional genome division also suggests the leading role of slow dividing and post mitotic cells in triggering and implementing the aging process.

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Section: Introductionmentioning

confidence: 77%

DNA methylation meta-analysis confirms the division of the genome into two functional groups

Salnikov¹,

Goldberg

Sukumaran

et al. 2022

Preprint

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“…A common denominator of aging is the accumulation of genetic damage and a considerable decrease in the efficiency of its repair. In addition, numerous diseases of premature aging, such as Werner's syndrome and Bloom's syndrome, result from an increased accumulation of DNA damage [ 53 ]. SIRT7 has been reported to be rapidly and transiently recruited in a PARP1-dependent manner to DNA damage sites and is required for efficient double-strand break (DSB) repair via homologous recombination (HR) and non-homologous end joining (NHEJ) [ 4 , 17 , 30 , 31 ].…”

Section: Sirt7 Association With Agingmentioning

confidence: 99%

SIRT7 in the aging process

Lagunas‐Rangel

2022

Cell. Mol. Life Sci.

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Aging is the result of the accumulation of a wide variety of molecular and cellular damage over time. This has been associated with a number of features termed hallmarks of aging, including genomic instability, loss of proteostasis, telomere attrition, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and impaired intercellular communication. On the other hand, sirtuins are enzymes with an important role in aging and life extension, of which humans have seven paralogs (SIRT1 to SIRT7). SIRT7 is the least studied sirtuin to date, but it has been reported to serve important functions, such as promoting ribosomal RNA expression, aiding in DNA damage repair, and regulating chromatin compaction. Several studies have established a close relationship between SIRT7 and age-related processes, but knowledge in this area is still scarce. Therefore, the purpose of this review was to analyze how SIRT7 is associated with each of the hallmarks of aging, as well as with some of age-associated diseases, such as cardiovascular diseases, obesity, osteoporosis, and cancer.

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“…Another possibility that tumor cells become resistant to a variety of anticancer drugs is their ability to repair DNA damage. Cancer cells can overcome DNA damage caused by chemotherapeutic drugs by activating several different repair mechanisms and pathways [ 48 , 49 ]. For example, if the repair pathway that is responsible for triggering cell death after chemotherapy therapy is deficient, an alternative repair pathway compensates and prompts cancer cells to repair the damage, leading to resistance to chemotherapy [ 50 ].…”

Section: Molecular Mechanisms Of Chemoresistance In Cancermentioning

confidence: 99%

Can Exposure to Environmental Pollutants Be Associated with Less Effective Chemotherapy in Cancer Patients?

Lagunas‐Rangel

Liu

Schiöth

2022

IJERPH

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Since environmental pollutants are ubiquitous and many of them are resistant to degradation, we are exposed to many of them on a daily basis. Notably, these pollutants can have harmful effects on our health and be linked to the development of disease. Epidemiological evidence together with a better understanding of the mechanisms that link toxic substances with the development of diseases, suggest that exposure to some environmental pollutants can lead to an increased risk of developing cancer. Furthermore, several studies have raised the role of low-dose exposure to environmental pollutants in cancer progression. However, little is known about how these compounds influence the treatments given to cancer patients. In this work, we present a series of evidences suggesting that environmental pollutants such as bisphenol A (BPA), benzo[a]pyrene (BaP), persistent organic pollutants (POPs), aluminum chloride (AlCl3), and airborne particulate matter may reduce the efficacy of some common chemotherapeutic drugs used in different types of cancer. We discuss the potential underlying molecular mechanisms that lead to the generation of this chemoresistance, such as apoptosis evasion, DNA damage repair, activation of pro-cancer signaling pathways, drug efflux and action of antioxidant enzymes, among others.

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The Role of DNA Repair in Cellular Aging Process

Cited by 11 publications

References 88 publications

DNA methylation meta-analysis confirms the division of the genome into two functional groups

DNA methylation meta-analysis confirms the division of the genome into two functional groups

SIRT7 in the aging process

Can Exposure to Environmental Pollutants Be Associated with Less Effective Chemotherapy in Cancer Patients?

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