Do mutations or DNA strand breaks cause human aging? Why?

I am not an expert in this field, but I am very interested and have researched to find an answer. Could you please review the response below to see if it is correct?

Mutations and DNA strand breaks significantly contribute to human aging. DNA damage accumulates over time due to various genotoxic insults and impaired repair mechanisms, leading to cellular dysfunction and senescence [1][2][3][7]. Specifically, DNA double-strand breaks (DSBs) have been implicated in aging-related decline in oocyte quality and overall reproductive capacity [4][10]. Additionally, mitochondrial DNA mutations, often arising from oxidative stress, contribute to aging by causing respiratory chain deficiencies and cellular energy deficits [5][8][9][12]. These cumulative genetic abnormalities disrupt cellular homeostasis, thereby accelerating the aging process and increasing susceptibility to age-related diseases [2][3][6][11].

Reference

[1] Hoeijmakers, J. (2009). DNA damage, aging, and cancer.. The New England journal of medicine, 361 15, 1475-85 .

[2] Ou, H., & Schumacher, B. (2018). DNA damage responses and p53 in the aging process.. Blood, 131 5, 488-495 .

[3] Maynard, S., Fang, E., Scheibye-Knudsen, M., Croteau, D., & Bohr, V. (2015). DNA Damage, DNA Repair, Aging, and Neurodegeneration.. Cold Spring Harbor perspectives in medicine, 5 10.

[4] Titus, S., Li, F., Stobezki, R., Akula, K., Unsal, E., Jeong, K., Dickler, M., Robson, M., Moy, F., Goswami, S., & Oktay, K. (2013). Impairment of BRCA1-Related DNA Double-Strand Break Repair Leads to Ovarian Aging in Mice and Humans. Science Translational Medicine, 5, 172ra21 - 172ra21.

[5] Larsson, N. (2010). Somatic mitochondrial DNA mutations in mammalian aging.. Annual review of biochemistry, 79, 683-706 .

[6] Rübe, C., Fricke, A., Widmann, T., Fürst, T., Madry, H., Pfreundschuh, M., & Rübe, C. (2011). Accumulation of DNA Damage in Hematopoietic Stem and Progenitor Cells during Human Aging. PLoS ONE, 6.

[7] Burhans, W., & Weinberger, M. (2007). DNA replication stress, genome instability and aging. Nucleic Acids Research, 35, 7545 - 7556.

[8] Zapico, S. C., & Ubelaker, D. (2013). mtDNA Mutations and Their Role in Aging, Diseases and Forensic Sciences.. Aging and disease, 4 6, 364-80 .

[9] Gredilla, R. (2010). DNA Damage and Base Excision Repair in Mitochondria and Their Role in Aging. Journal of Aging Research, 2011.

[10] Lin, W. T., Titus, S., Moy, F., Ginsburg, E., & Oktay, K. (2017). Ovarian Aging in Women With BRCA Germline Mutations. The Journal of Clinical Endocrinology & Metabolism, 102, 3839–3847.

[11] Pan, M., Li, K., Lin, S., & Hung, W. (2016). Connecting the Dots: From DNA Damage and Repair to Aging. International Journal of Molecular Sciences, 17.

[12] Baines, H. L., Turnbull, D., & Greaves, L. C. (2014). Human stem cell aging: do mitochondrial DNA mutations have a causal role?. Aging Cell, 13, 201 - 205.

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