Abstract
Telomeres play a fundamental role in the maintenance of genomic integrity at a cellular level, and average leukocyte telomere length (LTL) has been proposed as a biomarker of organismal aging. However, studies tracking LTL across the entire life course of individuals are lacking. Here, we examined lifelong patterns of variation in LTL among four birth cohorts of female Soay sheep (Ovis aries) that were longitudinally monitored and sampled from birth to death. Over the first 4months of life, there was within-individual loss of LTL, consistent with findings in the human and primate literature, but there was little evidence of consistent LTL loss associated with age after this point. Overall, we observed only weak evidence of individual consistency in LTL across years and over the entire lifespan: Within-individual variation was considerable, and birth cohorts differed markedly in their telomere dynamics. Despite the high levels of LTL variation within the lifetimes of individuals, there remained significant associations between LTL and longevity. Detailed analysis of the longitudinal data set showed that this association was driven by improved survival of individuals with longer LTL over the first 2years of life. There was no evidence that LTL predicted survival in later adulthood. Our data provide the first evidence from a mammal that LTL can predict mortality and lifespan under natural conditions, and also highlight the potentially dynamic nature of LTL within the lifetimes of individuals experiencing a complex and highly variable environment.
Highlights
Telomeres are DNA–protein complexes at the ends of linear chromosomes that protect against DNA degradation, fusion, and recognition as a DNA discontinuity or break (De Lange, 2004)
We found that the population-level relationship between mean relative leukocyte telomere length (RLTL) and age was complex and driven both by within-individual changes and (A)
There was a notable decline in RLTL between birth and 4 months of age followed by an increase until 64 months (5 years old), and a secondary decline thereafter (Fig. 2A)
Summary
Telomeres are DNA–protein complexes at the ends of linear chromosomes that protect against DNA degradation, fusion, and recognition as a DNA discontinuity or break (De Lange, 2004). The immature germline and highly proliferative cell types express an enzyme called the telomerase reverse transcriptase (TERT) that replenishes telomeric tracts through the reverse transcription of its telomerase RNA component (hTR) (Cech, 2004). Telomere erosion in specific tissues has been documented during organismal aging, which has led to the notion that TL may affect organismal lifespan as well as cellular lifespan (Vera et al, 2012; Lopez-Otin et al, 2013). In laboratory murine strains, an increase in telomerase expression ameliorates tissue decline with age and results in an increase in average lifespan (de Jesus et al, 2011; Vera et al, 2013). Whether short telomeres predict subsequent lifespan and healthspan in organisms outside the laboratory, including humans, and whether cellular TL could have any causal effect on organismal function remain questions under intense current investigation (Monaghan & Haussmann, 2006; Aubert & Lansdorp, 2008)
Sign-in/Register to view highlights & summary 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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
