Telomere attrition: metabolic regulation and signalling function?

Abstract

Stress exposure can leave long-term footprints within the organism, like in telomeres (TLs), protective chromosome caps that shorten during cell replication and following exposure to stressors. Short TLs are considered to indicate lower fitness prospects, but why TLs shorten under stressful conditions is not understood. Glucocorticoid hormones (GCs) increase upon stress exposure and are thought to promote TL shortening by increasing oxidative damage. However, evidence that GCs are pro-oxidants and oxidative stress is causally linked to TL attrition is mixed . Based on new biochemical findings, we propose the metabolic telomere attrition hypothesis: during times of substantially increased energy demands, TLs are shortened as part of the transition into an organismal ‘emergency state’, which prioritizes immediate survival functions over processes with longer-term benefits. TL attrition during energy shortages could serve multiple roles including amplified signalling of cellular energy debt to re-direct critical resources to immediately important processes. This new view of TL shortening as a strategy to resolve major energetic trade-offs can improve our understanding of TL dynamics. We suggest that TLs are master regulators of cell homeostasis and propose future research avenues to understand the interactions between energy homeostasis, metabolic regulators and TL.

Impact of continuous predator threat on telomere dynamics in parent and nestling pied flycatchers

“…A recent hypothesis also suggests that telomere shortening may increase during times of substantially increased energy demands due to specific metabolic adjustments (Casagrande and Hau 2019). For instance, a study on humans found that individuals with high physical activity had shorter telomeres than individuals with moderate physical activity (Ludlow et al 2008).…”

Ageing before birth: pace and stability of prenatal growth affect telomere dynamics

“…Prenatal exposure to glucocorticoids has been shown to accelerate telomere shortening [25], and therefore variation in prenatal glucocorticoid levels linked to incubation temperature stability could contribute to the observed differences in hatching telomere length, since we found that embryos experiencing unstable incubation conditions had higher plasma glucocorticoid levels and shorter telomeres at hatching. This effect on telomeres could be a consequence of either reduced telomerase activity ( [48], but see [49]) or reprogramming of cellular metabolism as recently proposed by the metabolic telomere attrition hypothesis [32]. However, shorter telomeres at hatching in the high temperature group could not be explained by differences in prenatal glucocorticoid exposure, nor by oxidative stress (see above).…”

“…Additionally, it is important to identify the underlying mechanisms driving telomere shortening in response to prenatal conditions. While oxidative stress is a first obvious candidate [13], glucocorticoid hormones have been suggested to influence prenatal telomere shortening [25], in a manner that could be independent of oxidative stress but linked to cellular metabolic reprogramming [32].…”

Flexibility Is Costly: Hidden Physiological Damage From Seasonal Phenotypic Transitions in Heterothermic Species

“…Telomere shortening during this seasonal transition may be an adaptive response. Indeed, this attrition would contribute to the amplification of the signaling of metabolic debt and therefore to the prioritization of somatic maintenance processes ( Casagrande and Hau, 2019 ). In this respect, telomerase, whose activity varies across species, cell types and life stages ( Gomes et al, 2010 ), represents the most widespread repair mechanism in normal cells.…”