Connecting the Dots: From DNA Damage and Repair to Aging

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2016 May 11

PMID 27164092

Citations 38

Authors

Mei-Ren Pan

Kaiyi Li

Shiaw-Yih Lin

Wen-Chun Hung

Affiliations

Soon will be listed here.

Abstract

Mammalian cells evolve a delicate system, the DNA damage response (DDR) pathway, to monitor genomic integrity and to prevent the damage from both endogenous end exogenous insults. Emerging evidence suggests that aberrant DDR and deficient DNA repair are strongly associated with cancer and aging. Our understanding of the core program of DDR has made tremendous progress in the past two decades. However, the long list of the molecules involved in the DDR and DNA repair continues to grow and the roles of the new "dots" are under intensive investigation. Here, we review the connection between DDR and DNA repair and aging and discuss the potential mechanisms by which deficient DNA repair triggers systemic effects to promote physiological or pathological aging.

Citing Articles

The kinetics of uracil-N-glycosylase distribution inside replication foci.

Ligasova A, Frydrych I, Pisklakova B, Friedecky D, Koberna K Sci Rep. 2025; 15(1):3026.

PMID: 39849039 PMC: 11757751. DOI: 10.1038/s41598-024-84408-x.

Aging and cancer: Clinical role of tumor markers in the geriatric population (Review).

Sundaresan S, Rajapriya P, Lavanya S Med Int (Lond). 2024; 4(3):21.

PMID: 39640494 PMC: 11618985. DOI: 10.3892/mi.2024.145.

Gerotherapeutics: aging mechanism-based pharmaceutical and behavioral interventions to reduce cancer racial and ethnic disparities.

Mandelblatt J, Antoni M, Bethea T, Cole S, Hudson B, Penedo F J Natl Cancer Inst. 2024; 117(3):406-422.

PMID: 39196709 PMC: 11884862. DOI: 10.1093/jnci/djae211.

Chronic HIV Transcription, Translation, and Persistent Inflammation.

Kilroy J, Leal A, Henderson A Viruses. 2024; 16(5).

PMID: 38793632 PMC: 11125830. DOI: 10.3390/v16050751.

Crosstalk between DNA Damage Repair and Metabolic Regulation in Hematopoietic Stem Cells.

Xu J, Fei P, Simon D, Morowitz M, Mehta P, Du W Cells. 2024; 13(9.

PMID: 38727270 PMC: 11083014. DOI: 10.3390/cells13090733.

References

Seviour E, Lin S . The DNA damage response: Balancing the scale between cancer and ageing. Aging (Albany NY). 2010; 2(12):900-7. PMC: 3034178. DOI: 10.18632/aging.100248. View

Tyner S, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H . p53 mutant mice that display early ageing-associated phenotypes. Nature. 2002; 415(6867):45-53. DOI: 10.1038/415045a. View

Caldecott K . Protein ADP-ribosylation and the cellular response to DNA strand breaks. DNA Repair (Amst). 2014; 19:108-13. DOI: 10.1016/j.dnarep.2014.03.021. View

Lombard D, Chua K, Mostoslavsky R, Franco S, Gostissa M, Alt F . DNA repair, genome stability, and aging. Cell. 2005; 120(4):497-512. DOI: 10.1016/j.cell.2005.01.028. View

Wong K, Maser R, Bachoo R, Menon J, Carrasco D, Gu Y . Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature. 2003; 421(6923):643-8. DOI: 10.1038/nature01385. View

Bertola D, Cao H, Albano L, Oliveira D, Kok F, Marques-Dias M . Cockayne syndrome type A: novel mutations in eight typical patients. J Hum Genet. 2006; 51(8):701-705. DOI: 10.1007/s10038-006-0011-7. View

Scheibye-Knudsen M, Mitchell S, Fang E, Iyama T, Ward T, Wang J . A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in cockayne syndrome. Cell Metab. 2014; 20(5):840-855. PMC: 4261735. DOI: 10.1016/j.cmet.2014.10.005. View

Campisi J . Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005; 120(4):513-22. DOI: 10.1016/j.cell.2005.02.003. View

Zeman M, Cimprich K . Causes and consequences of replication stress. Nat Cell Biol. 2013; 16(1):2-9. PMC: 4354890. DOI: 10.1038/ncb2897. View

10.

Li H, Vogel H, Holcomb V, Gu Y, Hasty P . Deletion of Ku70, Ku80, or both causes early aging without substantially increased cancer. Mol Cell Biol. 2007; 27(23):8205-14. PMC: 2169178. DOI: 10.1128/MCB.00785-07. View

11.

Dobbelstein M, Sorensen C . Exploiting replicative stress to treat cancer. Nat Rev Drug Discov. 2015; 14(6):405-23. DOI: 10.1038/nrd4553. View

12.

Vyjayanti V, Rao K . DNA double strand break repair in brain: reduced NHEJ activity in aging rat neurons. Neurosci Lett. 2005; 393(1):18-22. DOI: 10.1016/j.neulet.2005.09.053. View

13.

Hoeijmakers J . DNA damage, aging, and cancer. N Engl J Med. 2009; 361(15):1475-85. DOI: 10.1056/NEJMra0804615. View

14.

Baker D, Wijshake T, Tchkonia T, LeBrasseur N, Childs B, van de Sluis B . Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011; 479(7372):232-6. PMC: 3468323. DOI: 10.1038/nature10600. View

15.

Gorbunova V, Seluanov A, Mao Z, Hine C . Changes in DNA repair during aging. Nucleic Acids Res. 2007; 35(22):7466-74. PMC: 2190694. DOI: 10.1093/nar/gkm756. View

16.

Hyun M, Lee J, Lee K, May A, Bohr V, Ahn B . Longevity and resistance to stress correlate with DNA repair capacity in Caenorhabditis elegans. Nucleic Acids Res. 2008; 36(4):1380-9. PMC: 2275101. DOI: 10.1093/nar/gkm1161. View

17.

Molinete M, Gradwohl G, Simonin F, de Murcia G . Zinc-binding domain of poly(ADP-ribose)polymerase participates in the recognition of single strand breaks on DNA. J Mol Biol. 1989; 210(1):229-33. DOI: 10.1016/0022-2836(89)90302-1. View

18.

Coppe J, Patil C, Rodier F, Sun Y, Munoz D, Goldstein J . Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008; 6(12):2853-68. PMC: 2592359. DOI: 10.1371/journal.pbio.0060301. View

19.

Starr M, Evers B, Saito H . Age-associated increase in cytokine production during systemic inflammation: adipose tissue as a major source of IL-6. J Gerontol A Biol Sci Med Sci. 2009; 64(7):723-30. PMC: 2844135. DOI: 10.1093/gerona/glp046. View

20.

Kunkel T . Celebrating DNA's Repair Crew. Cell. 2015; 163(6):1301-3. DOI: 10.1016/j.cell.2015.11.028. View