Abstract
Epidemiological studies have principally relied on measurements of telomere length (TL) in leucocytes, which reflects TL in other somatic cells. Leucocyte TL (LTL) displays vast variation across individuals—a phenomenon already observed in newborns. It is highly heritable, longer in females than males and in individuals of African ancestry than European ancestry. LTL is also longer in offspring conceived by older men. The traditional view regards LTL as a passive biomarker of human ageing. However, new evidence suggests that a dynamic interplay between selective evolutionary forces and TL might result in trade-offs for specific health outcomes. From a biological perspective, an active role of TL in ageing-related human diseases could occur because short telomeres increase the risk of a category of diseases related to restricted cell proliferation and tissue degeneration, including cardiovascular disease, whereas long telomeres increase the risk of another category of diseases related to increased proliferative growth, including major cancers. To understand the role of telomere biology in ageing-related diseases, it is essential to expand telomere research to newborns and children and seek further insight into the underlying causes of the variation in TL due to ancestry and geographical location.This article is part of the theme issue ‘Understanding diversity in telomere dynamics’.
Highlights
The effort to identify persons whose biological age is out of step with their calendrical age has largely fuelled the field of telomere epidemiology
Engineered deficiencies in telomerase and other telomere-maintenance proteins [1,2,3] have confirmed that short telomeres curtail the lifespan of mice, but only after several generations
That is because inbred strains of mice have very long telomeres; sustained deficiency in telomere maintenance across several generations is necessary to shorten telomeres to a length that impacts health and longevity of these mice
Summary
The effort to identify persons whose biological age is out of step with their calendrical age has largely fuelled the field of telomere epidemiology. The wide TL variation across newborns and children suggests a considerable influence of TL in early life on TL throughout the human life course [11,27] Such findings do not challenge the potential role of oxidative stress and inflammation during the life course in the association of short LTL with cardiovascular disease. This conclusion suggests that mechanisms other than, or in addition to, oxidative stress and inflammation during adulthood might explain LTL variation across the general population and TL disease association These include diminished replicative potential and perhaps compromised repair ability when TL is short and increased proliferative potential and increased risk of cancer when TL is long [94,95]. These findings indicate that the mere presence of senescent cells might bring about both tissue degeneration and cancer susceptibility through mechanisms that are telomere dependent and independent
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
