The Role of Telomeres in Senescence, Aging and Disease: Fiction and Reality

Telomeres are repetitive structures at the ends of linear chromosomes. Due to incomplete DNA replication at the end of linear DNA molecules, the so called “end replication problem”, telomeres shorten consecutively during cell division. In addition, telomere sequences are highly susceptible to oxidative stress damaging telomeres and resulting in their dysfunction even in non-dividing cells. Telomere shortening has been identified as one of the underlying causes for replicative senescence that can also contribute to aging due to the accumulation of senescent cells with advanced age in various tissues. These cells, in addition to an irreversible cell cycle arrest, are also characterized by a specific senescence-associated secretory phenotype (SASP) and hence increased inflammation. However, also postmitotic cells that do not shorten telomeres can have damaged and dysfunctional telomeres, undergo senescence without a specific cycle arrest and have a SASP. The influence of senescence on the aging process can be partially reversed by removing senescent cells from the body using senolytic agents. Many studies related to this topic, analyze predominantly blood leukocyte telomere length and suggest a direct causal relationship between telomeres, aging and diseases. Importantly, it is now more and more accepted that telomere length has a strong genetic element that is already obvious in newborns and might determine the trajectory of telomere dynamics through the entire adult life and thus pre-determine lifespan, aging and the susceptibility to various ageing-associated diseases. Moreover, there are additional factors such as oxidative stress and inflammation as well as lifestyle interventions that are able to influence telomere length (TL) and telomere shortening rate (TSR) during an individual’s lifetime. The review aims to raise awareness of the different factors that impact telomeres for a better understanding of the intricate relationship between telomeres, senescence, aging and age-related diseases.