Reflections on telomere dynamics and ageing-related diseases in humans

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’.

Early‐life telomere length predicts lifespan and lifetime reproductive success in a wild bird

“…Given that TL heritability can be substantial (Dugdale & Richardson, 2018), this raises the question why TL are not longer, suggesting that there may be balancing selection, related to fitness costs associated with a longer TL than currently observed. This suggests that also in wild animals, there may be a balance between benefits of long telomeres and benefits of short telomeres, as has been suggested in humans for TL versus cardiovascular disease and cancer risk (Aviv & Shay, 2018). Alternatively, the TL variance component that associates with fitness is independent of the heritable variance component, in which case there is no selection for longer telomeres to evolve; in this scenario, the TL fitness association can possibly be attributed to early-life conditions that impact early-life telomere dynamics.…”

“…Once telomeres shorten to a critical length, the cell enters a senescent state or initiates cell apoptosis (von Zglinicki et al, 2001). In addition, some evidence suggests that TL may also have a role in age-related diseases such as cardiovascular disease and cancer (Aviv & Shay, 2018). The accumulation of cells in these states impairs tissue renewal capacity and function, causing the symptoms associated with organismal senescence (Aubert & Lansdorp, 2008).…”

Understanding diversity in telomere dynamics

“…They provide a general conceptual framework for considering the role of body size in the evolution of tumour suppression mechanisms. Aviv and Shay [25] also consider the costs and benefits of short and long telomeres in shaping optimal telomere length in humans, with relatively long telomeres proving potential protection against cardiovascular disease, but increasing the risk of tumour formation. There is recent empirical evidence in support of this [26].…”

Life-long telomere attrition predicts health and lifespan in a large mammal

“…They shorten with the number of cell divisions in vitro as well as in response to oxidative stress and critically short telomeres trigger a DNA damage response that leads to replicative senescence or apoptosis (Harley, Futcher, & Greider, 1990;Olovnikov, 1973;Watson, 1972). In the last decade or so, measures of average telomere length (TL) taken from blood samples have emerged as an exciting biomarker of health across disciplines including biomedicine, epidemiology, ecology and evolutionary biology (Aviv & Shay, 2018;Harrington & Pucci, 2018;Wilbourn et al, 2018). Considerable among-and within-individual variation in TL has been observed, with a general pattern of rapid telomere attrition during early life and a plateau or slower decline thereafter (Aubert & Lansdorp, 2008;Baerlocher, Rice, Vulto, & Lansdorp, 2007).…”