- Shortening of telomeres is a natural biological process that occurs during each cell division and is closely linked to cellular aging, genomic stability, and disease development.
- Telomeres are repetitive nucleotide sequences (TTAGGG in humans) located at the ends of linear chromosomes, serving as protective caps that prevent the degradation of essential genetic information and guard against chromosome fusion or inappropriate repair mechanisms. They are bound by specialized proteins forming a protective complex known as the shelterin complex, which helps maintain chromosome integrity.
- With each round of DNA replication, a portion of the telomeric DNA is not fully replicated due to the so-called “end-replication problem.” As a result, telomeres shorten progressively every time a cell divides. In most somatic cells, where the enzyme telomerase is inactive or present at very low levels, this gradual shortening ultimately leads to a critical telomere length at which cells enter replicative senescence—a state of irreversible growth arrest—or undergo apoptosis (programmed cell death). This process is considered a key mechanism of biological aging and contributes to age-related decline in tissue function.
- Shortened telomeres are associated with a range of chronic diseases and conditions, including cardiovascular disease, type 2 diabetes, pulmonary fibrosis, and neurodegenerative disorders. Telomere shortening is also seen in individuals exposed to chronic psychological stress, inflammation, oxidative stress, and certain environmental toxins, all of which accelerate the erosion of telomeric DNA. In contrast, longer telomeres have been linked to a slower biological aging process and greater cellular longevity, although excessively long telomeres may sometimes be associated with increased cancer risk.
- In cancer biology, telomere shortening plays a dual role. On the one hand, it can act as a barrier to uncontrolled proliferation by inducing senescence or apoptosis. On the other hand, in tumorigenesis, some cells bypass this barrier by reactivating telomerase or using an alternative lengthening mechanism (ALT), enabling them to maintain telomere length and become immortalized, which is a hallmark of many cancer types.
- In stem cells, germ cells, and certain immune cells, telomerase remains active, allowing these cells to maintain longer telomeres and support tissue regeneration and repair. Therapeutic strategies aimed at slowing telomere attrition, activating telomerase, or protecting telomeres are being explored in the fields of anti-aging research, regenerative medicine, and oncology.
