Telomeres, the loop tying cancer to organismal life‐histories

Abstract

Recent developments in telomere and cancer evolutionary ecology demonstrate a very complex relationship between the need of tissue repair and controlling the emergence of abnormally proliferating cells. The trade‐off is balanced by natural and sexual selection and mediated via both intrinsic and environmental factors. Here, we explore the effects of telomere‐cancer dynamics on life history traits and strategies as well as on the cumulative effects of genetic and environmental factors. We show that telomere‐cancer dynamics constitute an incredibly complex and multifaceted process. From research to date, it appears that the relationship between telomere length and cancer risk is likely nonlinear with good evidence that both (too) long and (too) short telomeres can be associated with increased cancer risk. The ability and propensity of organisms to respond to the interplay of telomere dynamics and oncogenic processes, depends on the combination of its tissue environments, life history strategies, environmental challenges (i.e., extreme climatic conditions), pressure by predators and pollution, as well as its evolutionary history. Consequently, precise interpretation of telomere‐cancer dynamics requires integrative and multidisciplinary approaches. Finally, incorporating information on telomere dynamics and the expression of tumour suppressor genes and oncogenes could potentially provide the synergistic overview that could lay the foundations to study telomere‐cancer dynamics at ecosystem levels.

A unified framework for evolutionary genetic and physiological theories of aging

“…Second, if the costly nature of telomere maintenance were to be established, experimental approaches would need to demonstrate that selection for an increased allocation towards growth or reproductive effort happens at the expense to an allocation towards the broad telomeric maintenance component, or vice-versa ( Fig 2 ). However, several lines of evidence suggest that telomerase repression in somatic cells is adaptive, as short telomeres buffer the risk of cell proliferation once a cell becomes malignant (see [ 86 , 87 ] for reviews). The relative allocation of resources towards telomere maintenance mechanisms, such as telomerase activation (at the expense of an allocation towards growth and reproduction), and its benefits in terms of fitness should be largely modulated by the balance between cancer risk and aging, which itself depends on both local conditions and species life history [ 87 ].…”

“…However, several lines of evidence suggest that telomerase repression in somatic cells is adaptive, as short telomeres buffer the risk of cell proliferation once a cell becomes malignant (see [ 86 , 87 ] for reviews). The relative allocation of resources towards telomere maintenance mechanisms, such as telomerase activation (at the expense of an allocation towards growth and reproduction), and its benefits in terms of fitness should be largely modulated by the balance between cancer risk and aging, which itself depends on both local conditions and species life history [ 87 ]. Therefore, even if telomerase expression buffers biological aging [ 88 ], natural selection could favor, under high cancer risk, the allocation of resources towards DNA repair mechanisms other than telomere maintenance.…”

Integrating telomere biology into the ecology and evolution of natural populations: Progress and prospects

“…Altogether, elucidating the ecology of gene expression and epigenetics in telomere maintenance across natural populations should therefore be considered an important task for the future. Ujarvi et al (2022) discuss what is known about cancer and telomeres in the wild, a topic of considerable interest since telomeres have historically been studied in the context of cancer, with somatic downregulation of telomerase postulated as a tumour protection mechanism in large bodies/long lived species. Telomerase activation has been identified as critical mutations that are associated with malignant cells.…”

“…Telomerase activation has been identified as critical mutations that are associated with malignant cells. Ujarvi et al (2022) emphasize that telomere‐cancer dynamics constitute a complex and a multifaceted process, in part because in humans both (too) long and (too) short telomeres can be associated with an increased cancer risk. Whether similar effects can be observed in natural populations of other species remains to be seen.…”

Editorial 2023

“…Additional studies also emphasize that what qualifies as a stressor depends greatly on the biology of the organism (Friesen et al, 2022; Wood et al, 2022), and demonstrate there is much to be gained by examining telomere dynamics across diverse forms of life (Bae et al, 2022; Boonekamp et al, 2022; McLennan et al, 2022; Power et al, 2022; Rouan et al, 2022). The third suite of articles in this special issue addresses the idea that telomeres may mediate life history trade‐offs, examining correlations between telomere length and reproductive fitness (Heidinger et al, 2022; Kauzálová et al, 2022; Ravindran et al, 2022; Sepp et al, 2022) physical state (e.g., body mass, size: Atema et al, 2022; Le Pepke, Kvalnes, Rønning, et al, 2022), and cancer prevalence (Le Pepke & Eisenberg, 2022; Ujvari et al, 2022) in natural and experimental systems. A final group of manuscripts explores the intriguing nature of heritability of telomere length and rate of shortening (Bauch et al, 2022; Kärkkäinen, Briga, et al 2022; Le Pepke, Kvalnes, Lundregan, et al, 2022; Sparks et al, 2022; Vedder et al, 2022).…”