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Telomeres are protein structures located at the ends of each eukaryotic DNA chromosomal arm. These chromosomal caps are 1 of the most important structures that preserve the structural integrity of linear DNA during each cycle of replication.[1] Functions of telomeres include protecting the ends of the DNA from binding to one another and to itself, allowing for complete chromosomal replication, and serving as a molecular timer by controlling the lifespan of a eukaryotic cell. Telomeres also prevent the free ends of the chromosome from appearing as DNA double-stranded breaks, which in turn safeguards the ends from accidental DNA repair.[2] Telomeres play a significant role in cellular senescence in humans and have made major contributions to human aging. Pathologically, dysregulated expression of the telomere synthesis mechanism causes cellular immortality, leading to potential oncogenesis and tumorigenesis.[3]

Cellular Senescence Telomeres play a crucial role in cellular senescence and, thus, biological aging. Cellular senescence refers to the irreversible loss of cellular division capability. The end replication problem, which describes the loss of base pairs during each S phase of cellular synthesis, can expose the ends of the DNA of a somatic cell, activating a process called DNA damage response. The purpose of this phenomenon is to prevent abnormal fusion of exposed chromosomal ends as well as chromosomal instability. The telomeres shorten without telomere elongation, characteristic of most somatic cells. Telomerase can elongate telomere structures; however, with persistent telomeric DNA damage response activation, a senescence-initiating signal can be elicited in addition to DNA damage. Cellular or replicative senescence also initiates when the telomere shortens to below a critical length.[25][26] DNA damage response involves multiple cellular signaling pathways that activate cell cycle checkpoints to prevent the formation of potentially pathophysiologic mutations.[27] In cancer cells, as described later under clinical significance, unlimited self-renewal capacity is acquired through uninhibited telomerase activation.[13]