All's well that ends well: why large species have short telomeres

Abstract

Among mammal species, almost all life-history traits are strongly size dependent. This size dependence even occurs at a molecular level. For example, both telomere length and telomerase expression show a size-dependent threshold. With some exceptions, species smaller than approximately 2 kg express telomerase, while species larger than that do not. Among species greater than approximately 5 kg, telomeres tend to be short-less than 25 kb-while among smaller species, some species have short and some have long telomeres. Here, we present a model to explore the role of body size-dependent trade-offs in shaping this threshold. We assume that selection favours short telomeres as a mechanism to protect against cancer. At the same time, selection favours long telomeres as a protective mechanism against DNA damage and replicative senescence. The relative importance of these two selective forces will depend on underlying intrinsic mortality and risk of cancer, both of which are size-dependent. Results from this model suggest that a cost-benefit model for the evolution of telomere length could explain phylogenetic patterns observed within the Class Mammalia. In addition, the model suggests a general conceptual framework to think about the role that body size plays in the evolution of tumour suppressor mechanisms.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.

From zygote to a multicellular soma: body size affects optimal growth strategies under cancer risk

“…telomerase expression observed in most human tumours (Kim et al, 1994), allowing tumour cells to divide without hitting the Hayflick limit (Blasco, 2005;Shay and Wright, 2019). Comparative studies have revealed correlations between body size and/or lifespan and telomerase activity and telomere length (Seluanov et al, 2007;Gomes et al, 2011), a pattern also predicted by theory (Risques and Promislow, 2018). For example, the finding that telomerase expression is repressed in somatic tissues of humans and larger mammals (Kim et al, 1994;Gomes et al, 2011) fits in well with the idea that telomerase expression is not a risk-free way to increase lifespan.…”

The role of telomeres in the mechanisms and evolution of life-history trade-offs and ageing

“…Accordingly, telomerase knock-out experiments in mice have been found to inhibit cancer inception and progression [ 86 ], fuelling interest in the therapeutic potential of anti-telomerase treatments in the fight against cancer [ 67 ]. Furthermore, comparative studies of mammals are suggestive of evolutionary changes in telomeric traits consistent with a function in tumour suppression: larger bodied species, whose larger number of cells are collectively expected to pose a greater cancer risk, tend to have somatic cells with shorter telomeres and lower levels of telomerase expression, which together may increase the stringency of telomere-mediated cancer surveillance ([ 27 , 67 , 74 , 84 ], see also [ 87 ] for supporting theory).…”

In medio stat virtus : unanticipated consequences of telomere dysequilibrium

“…An increasing number of human cancer types exhibit mutations in the TERT promoter that lead to upregulated telomerase activity or mutations within shelterin components such as POT1, both of which often result in a longer average telomere length [ 49 , 50 ]. Thus, deviations from the norm (too long or too short) may both signal a loss of telomere integrity, although presumably through distinct mechanisms (as below; see also [ 51 ]).…”