DNA Repair

06 July 2023

DNA Repair and Bio-Rejuvenation: The Blueprint to Reverse Aging

Introduction

The role of DNA repair in bio-rejuvenation has been a topic of intense research in the field of biogerontology. As DNA damage accumulates with age, understanding and enhancing DNA repair mechanisms could potentially reverse aging and extend both the healthspan and lifespan (1).

Understanding DNA Damage and Repair

DNA damage occurs continuously in cells due to exposure to environmental toxins, radiation, and normal cellular processes. The human body employs various DNA repair mechanisms to maintain genomic integrity, including direct repair, base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), and double-strand break repair (DSBR) (2).

Despite these repair processes, damage can accumulate, resulting in genetic mutations and cellular dysfunction, which contribute to aging and age-related diseases such as cancer, neurodegenerative disorders, and cardiovascular disease (3).

DNA Repair and Aging

The connection between DNA repair and aging is well-established. As the efficiency of DNA repair mechanisms declines with age, there is an increase in DNA damage, genomic instability, and cellular senescence, contributing to the aging process and the onset of age-related diseases (4).

Notably, several genetic disorders characterized by premature aging, such as Werner syndrome and Hutchinson-Gilford progeria syndrome, are linked to defects in DNA repair mechanisms (5).

DNA Repair in Bio-Rejuvenation

Enhancing DNA repair could slow down or reverse the biological aging process, extending healthspan and potentially lifespan. Recent research in this area has focused on several strategies:

• DNA repair enzymes: The use of enzymes involved in DNA repair, such as telomerase, has shown potential in reducing cellular aging. These enzymes can potentially extend the lifespan of cells and delay age-related decline (6).

• Caloric restriction and DNA repair: Studies have shown that caloric restriction can enhance DNA repair and extend lifespan in various organisms. The mechanisms involved are not yet fully understood, but it is thought that caloric restriction reduces oxidative stress, which in turn reduces DNA damage (7).

• Pharmacological interventions: Certain drugs and compounds, such as poly(ADP-ribose) polymerase (PARP) inhibitors and NAD+ precursors, have been shown to enhance DNA repair and extend lifespan in model organisms (8).

Conclusion

While the full potential of DNA repair in bio-rejuvenation is yet to be realized, the existing evidence strongly supports the role of DNA repair mechanisms in aging and age-related diseases. By further elucidating the underlying mechanisms, we can develop novel strategies to improve healthspan and lifespan through enhanced DNA repair.

References

• López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

• Jeggo, P. A., Pearl, L. H., & Carr, A. M. (2016). DNA repair, genome stability and cancer: a historical perspective. Nature Reviews Cancer, 16(1), 35-42.

• Vijg, J., & Suh, Y. (2013). Genome instability and aging. Annual review of physiology, 75, 645-668.

• Gorbunova, V., Seluanov, A., & Mao, Z. (2007). DNA double strand break repair, aging and the chromatin connection. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 621(1-2), 9-22.

• Martin, G. M. (2005). Genomic instability and aging: clinical and experimental evidence. Current gerontology and geriatrics research, 2(1), 17-27.

• de Lange, T. (2005). Shelterin: the protein complex that shapes and safeguards human telomeres. Genes & development, 19(18), 2100-2110.

• Colman, R. J., Anderson, R. M., Johnson, S. C., Kastman, E. K., Kosmatka, K. J., Beasley, T. M., ... & Weindruch, R. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science, 325(5937), 201-204.

• Fang, E. F., Kassahun, H., Croteau, D. L., Scheibye-Knudsen, M., Marosi, K., Lu, H., ... & Clish, C. B. (2016). NAD+ replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair. Cell metabolism, 24(4), 566-581.