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. Author manuscript; available in PMC: 2024 Oct 1.
Published in final edited form as: Exerc Sport Sci Rev. 2023 Jun 7;51(4):150–160. doi: 10.1249/JES.0000000000000324

Figure 1. Telomere and telomerase biology and their role in cellular senescence.

Figure 1.

Telomeres are specialized DNA structures at the end of chromosomes. Shelterin is a protein complex that coordinates telomere structure formation. Shelterin consists of six proteins including TRF1, TRF2, RAP1, TIN2, POT1 and TPP1. TRF1 and TRF2 bind to double-stranded DNA, while POT1 binds to single-stranded DNA. RAP1 interacts with TRF2, and TIN2 interacts with TRF1 and TRF2. In telomere-looping structure, TPP1 interacts with TIN2 and POT1 (A). When telomeres are long and intact, the telomeres are functional and inhibit the DNA damage response that induces replicative senescence in cells. However, when telomeres become critically short by cell division and/or DNA damage, the DNA damage response (DDR) is induced and cells enter cellular senescence (i.e., irreversible cessation of cell division). Telomeric DNA damage-induced DNA damage response can also be telomere length independent and result in telomere associated DNA damage foci (TAFs) or telomere damage induced foci (TIFs) which can also induce cellular senescence, even in post-mitotic cell types such as skeletal muscle and cardiac muscle (B). Telomerase is a reverse transcriptase enzyme that can synthesize telomere repeats. The two minimal essential components for telomerase activity are the protein catalytic component, telomerase reverse transcript (TERT), and the RNA template (telomerase RNA component, TERC or TR) (C). Abbreviation: TRF1 (Telomere Repeat binding Factor 1), TRF2 (Telomere Repeat binding Factor 2), RAP1 (Repressor / Activator Protein 1), POT1 (Protection of Telomere 1), TPP1 (adrenocortical dysplasia homolog shelterin complex subunit and Telomerase Recruitment Factor), TIN2 (telomere repeat binding factor 1 interacting protein 2). Created with BioRender.com.