Muller, H. J. The remaking of chromosomes. Collecting Net, Woods Hole 13, 181–198 (1938).

Google Scholar 

McClintock, B. The behavior in successive nuclear divisions of a chromosome broken at meiosis. Proc. Natl Acad. Sci. USA 25, 405–416 (1939).

Article  CAS  PubMed  PubMed Central  Google Scholar 

McClintock, B. The stability of broken ends of chromosomes in Zea mays. Genetics 26, 234–282 (1941).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hayflick, L. & Moorhead, P. S. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25, 585–621 (1961).

Article  CAS  PubMed  Google Scholar 

Hayflick, L. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 37, 614–636 (1965).

Article  CAS  PubMed  Google Scholar 

Olovnikov, A. Principle of marginotomy in the synthesis of polynucleotides at a template. Dokl. Biochem. Biophys. 201, 394–397 (1971).

Google Scholar 

Olovnikov, A. M. Telomeres, telomerase, and aging: origin of the theory. Exp. Gerontol. 31, 443–448 (1996).

Article  CAS  PubMed  Google Scholar 

Watson, J. D. Origin of concatemeric T7 DNA. Nat. New Biol. 239, 197–201 (1972).

Article  CAS  PubMed  Google Scholar 

Greider, C. W. & Blackburn, E. H. Identification of a specific telomere terminal transferase activity in tetrahymena extracts. Cell 43, 405–413 (1985).

Article  CAS  PubMed  Google Scholar 

Moyzis, R. K. et al. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc. Natl Acad. Sci. USA 85, 6622–6626 (1988).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morin, G. B. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell 59, 521–529 (1989).

Article  CAS  PubMed  Google Scholar 

Prowse, K. R., Avilion, A. A. & Greider, C. W. Identification of a nonprocessive telomerase activity from mouse cells. Proc. Natl Acad. Sci. USA 90, 1493–1497 (1993).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Harley, C. B., Futcher, A. B. & Greider, C. W. Telomeres shorten during ageing of human fibroblasts. Nature 345, 458–460 (1990).

Article  CAS  PubMed  Google Scholar 

Hastie, N. D. et al. Telomere reduction in human colorectal carcinoma and with ageing. Nature 346, 866–868 (1990).

Article  CAS  PubMed  Google Scholar 

Schmidt, T. T. et al. High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer. Nat. Commun. 15, 5149 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

d’Adda di Fagagna, F. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194–198 (2003).

Article  PubMed  Google Scholar 

Takai, H., Smogorzewska, A. & de Lange, T. DNA damage foci at dysfunctional telomeres. Curr. Biol. 13, 1549–1556 (2003).

Article  CAS  PubMed  Google Scholar 

Shay, J. W., Pereira-Smith, O. M. & Wright, W. E. A role for both RB and p53 in the regulation of human cellular senescence. Exp. Cell Res. 196, 33–39 (1991).

Article  CAS  PubMed  Google Scholar 

Bodnar, A. G. et al. Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349–352 (1998).

Article  CAS  PubMed  Google Scholar 

Smogorzewska, A. & de Lange, T. Different telomere damage signaling pathways in human and mouse cells. EMBO J. 21, 4338–4348 (2002). This paper shows that TIF-induced cellular senescence relies on two checkpoint pathways in humans, p16INK4aand the p53–p21 pathway, but only on the latter in mouse models.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, N. W. et al. Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011–2015 (1994).

Article  CAS  PubMed  Google Scholar 

Nassour, J. et al. Autophagic cell death restricts chromosomal instability during replicative crisis. Nature 565, 659–663 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maciejowski, J. & Lange, T. D. Telomeres in cancer: tumour suppression and genome instability. Nat. Rev. Mol. Cell Biol. 18, 175–186 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Counter, C. M. et al. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J. 11, 1921–1929 (1992).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chin, L. et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97, 527–538 (1999).

Article  CAS  PubMed  Google Scholar 

Bertuch, A. A. The molecular genetics of the telomere biology disorders. RNA Biol. 13, 696–706 (2016).

Article  PubMed  Google Scholar 

Anderson, R. et al. Length-independent telomere damage drives post-mitotic cardiomyocyte senescence. EMBO J. 38, e100492 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Blasco, M. A. et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25–34 (1997). This study generates a telomerase-activity-deficient mouse model through deletion of mTR. Successive inbreeding of these mice reveals a generational reduction in telomere sequence length, which eventually results in telomere dysfunction.

Article  CAS  PubMed  Google Scholar 

Lee, H.-W. et al. Essential role of mouse telomerase in highly proliferative organs. Nature 392, 569–574 (1998).

Article  CAS  PubMed  Google Scholar 

Herrera, E. et al. Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO J. 18, 2950–2960 (1999).

Article  CAS  PubMed  PubMed Central  Google Scholar 

He, S. & Sharpless, N. E. Senescence in health and disease. Cell 169, 1000–1011 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rossiello, F., Jurk, D., Passos, J. F. & Fagagna, F. D. A. D. Telomere dysfunction in ageing and age-related diseases. Nat. Cell Biol. 24, 135–147 (2022).

Article  CAS  PubMed  PubMed Central