Can DNA Beat Aging
Aging is a biological process that results in a gradual loss of physiological integrity due to the waning of functional properties in humans and organisms. One of the primary aspects associated with aging is mitochondrial dysfunction, and the amassing of genetic damage as individuals grow older. In actuality, the defective preserve of nuclear and mitochondrial DNA plays an essential role in the aging process. As people become older, the integrity and constancy of DNA are defied by exogenous physical, chemical, or biological agents, besides endogenous progressions, such as DNA replication faults, unprompted hydrolytic responses, and responsive oxygen sort. Although genetic material repair systems have developed a complex network that responds to these damages, their adeptness declines with age, which implies that DNA change cannot beat aging.
The aging process and DNA variations are closely related. First, aging in humans is a natural process resulting from the accumulation of cellular damage. Second, the progression is characterized by numerous aspects such as genomic unsteadiness, telomere abrasion, epigenetic changes, cellular senescence, mitochondrial dysfunction, and transformed intercellular communication, among others. Although the aging is associated with damaged cellular elements, DNA is the primary key target in the progression. As Deelen (2013) asserts, genomic unsteadiness is the central facet of aging. Genome instability is considered as a leading factor in aging since the damaged DNA, DNA replication, and mutations accrue as individuals’ age progresses. Similarly, the concept that faults in genome actions primarily trigger early aging signs accentuates the significant role of genome integrity in aging. Overall, molecular bases that relate to DNA change or damage are linked to the aging process.
Whereas DNA encodes essential information regarding cellular content and function, age-related changes in mismatch repair (MMR) enhance the aging process. Biologically, the predominant interpretation of the causes of aging is the accretion of somatic damage. Moreover, DNA destruction leads to cell cycle arrest, cell death, or mutation. Although most of the mutations do not impair the cell, the process can result in the deregulation of transcription sequence. Normally, the MMR removes mispaired bases due to mutation faults, re-amalgamation between defectively matched patterns, and deamination of 5-methyl-cytosine. In the aging process, MMR plays an essential role in continuing recurrent systems since mutations in MMR genes are associated with a significant instability of microsatellites that increases with aging (Neri et al., 2005). Despite the considerable role MMR plays, the function declines with age. A research by Gorbunova et al. (2007) indicates a weakening in MMR with an increase in vitro age. Therefore, the decline in MMR functions implies that DNA change cannot overcome age.
DNA cannot beat aging due to the declining nucleotide excision repair (NER) actions triggered by age. NER removes short strands of oligonucleotides enclosing impaired DNA bases. Moreover, NER entails the main pathway for fixing colossal DNA lesions. Two primary sub pathways can trigger NER: global genome NER (GG-NER) and the transcription-coupled NER. Both the two pathways join to finish the excision procedure through NER components such as RPA, XPA, TFIIH, XPD, XPB, XPG, and ERCC1–XPF, among other auxiliary proteins (Lagunas-Rangel & Bermúdez-Cruz, 2019). Nonetheless, NER’s activity declines with time, perhaps due to the transcriptional downregulation of NER genes, a changed protein function or procedure, and a drop in energy production. According to Lagunas-Rangel and Bermúdez-Cruz (2019), elderly aged human skin and fibroblasts exhibited reduced levels of XPB, PCNA, RPA, XPA, and p53. Furthermore, the authors assert that UVB-prompted pyrimidine dimers slowly removes manner among the elderly as compared to youths. Therefore, a decreased NER activity with age means that DNA change does not have a significant impact on age.
The changes that occur on the base excision repair (BER) contribute to the build-up of oxidative DNA lesions and mutations during aging. Normally, excision restoration removes lesions, which impairs one DNA strand. The excision repair is essential for restoring base damage triggered by reactive oxygen types. Overall, the BER pathway improves DNA damage from oxidation, deamination, alkylation, and other minor DNA changes that do not alter the complete structure of double helix. Nonetheless, the effectiveness of BER is impaired with age, an aspect that is supported by Zhang et al. (2020). Consequently, the BER pathway is futile when repairing age-down controlled DNA.
Whereas genetic material repair systems respond to DNA damages, their aptitude declines with age, which means that DNA change cannot beat aging. Aging results from the accumulation in different cellular elements, with DNA damage being the key constituent. Several insults affect DNA, either through endogenous features such as metabolism or exogenous aspects, for instance, radiation contact or exposure to lethal substances. Notably, DNA repair systems such as MMR, NER, and BER correct the damages caused to DNA. Nonetheless, the efficiency of the systems falls with age. This decline can be associated with essential proteins involved in DNA repair that significantly drop their expression due to age factors. Therefore, DNA changes are almost insignificant to the aging process.
