The evolution of CpG density and lifespan in conserved primate and mammalian promoters

McLain, Adam T.; Faulk, Christopher

doi:10.18632/aging.101413

Cited by 25 publications

(23 citation statements)

References 36 publications

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“…This hypothesis was strongly supported in an investigation showing that CpG density is correlated with lifespan among a set of conserved mammalian promoters 26 . McLain and Faulk 33 identified 1,079 promoters where the CpG density correlated with increasing lifespan (q < 0.05). This suggests a functional role for CpG density in the maximum lifespan of mammalian species.…”

Section: Introductionmentioning

confidence: 99%

A genomic predictor of lifespan in vertebrates

Mayne

Berry

Davies

et al. 2019

Sci Rep

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Biological ageing and its mechanistic underpinnings are of immense biomedical and ecological significance. Ageing involves the decline of diverse biological functions and places a limit on a species’ maximum lifespan. Ageing is associated with epigenetic changes involving DNA methylation. Furthermore, an analysis of mammals showed that the density of CpG sites in gene promoters, which are targets for DNA methylation, is correlated with lifespan. Using 252 whole genomes and databases of animal age and promotor sequences, we show a pattern across vertebrates. We also derive a predictive lifespan clock based on CpG density in a selected set of promoters. The lifespan clock accurately predicts maximum lifespan in vertebrates (R2 = 0.76) from the density of CpG sites within only 42 selected promoters. Our lifespan clock provides a wholly new method for accurately estimating lifespan using genome sequences alone and enables estimation of this challenging parameter for both poorly understood and extinct species.

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Section: Introductionmentioning

confidence: 99%

A genomic predictor of lifespan in vertebrates

Mayne

Berry

Davies

et al. 2019

Sci Rep

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“…For example, rhesus macaques ( Macaca mulatta ) exhibit many age‐related changes in physiological parameters similar to humans (Maestripieri & Hoffman, ; Smucny et al, ) and were the first primates in which caloric restriction was demonstrated to delay age‐related illness and mortality (Colman et al, ). Recent calls have been made for more research on effects of allostatic load on health and aging in primates (Edes & Crews, ; Maestripieri & Hoffman, ), and some work has taken advantage of the primate group to investigate evolutionary origins of senescence (Bronikowski et al, ) and genetic mechanisms of aging (de Magalhães & Church, ; McLain & Faulk, ). Yet, the great majority of aging studies in NHPs have focused on a few commonly studied species rather than cross‐species comparisons and none have focused on dysregulation per se.…”

Section: Introductionmentioning

confidence: 99%

Conservation of physiological dysregulation signatures of aging across primates

et al. 2019

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Two major goals in the current biology of aging are to identify general mechanisms underlying the aging process and to explain species differences in aging. Recent research in humans suggests that one important driver of aging is dysregulation, the progressive loss of homeostasis in complex biological networks. Yet, there is a lack of comparative data for this hypothesis, and we do not know whether dysregulation is widely associated with aging or how well signals of homeostasis are conserved. To address this knowledge gap, we use unusually detailed longitudinal biomarker data from 10 species of nonhuman primates housed in research centers and data from two human populations to test the hypotheses that (a) greater dysregulation is associated with aging across primates and (b) physiological states characterizing homeostasis are conserved across primates to degrees associated with phylogenetic proximity. To evaluate dysregulation, we employed a multivariate distance measure, calculated from sets of biomarkers, that is associated with aging and mortality in human populations. Dysregulation scores positively correlated with age and risk of mortality in most nonhuman primates studied, and signals of homeostatic state were significantly conserved across species, declining with phylogenetic distance. Our study provides the first broad demonstration of physiological dysregulation associated with aging and mortality risk in multiple nonhuman primates. Our results also imply that emergent signals of homeostasis are evolutionarily conserved, although with notable variation among species, and suggest promising directions for future comparative studies on dysregulation and the aging process.

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“…Previous research has found the frequency of cytosine-phosphate-guanine (CpG) sites in selected gene promoters can be predictive of lifespan [11,12]. This provides an alternative method to predicting lifespan in long-lived species.…”

Section: Open Accessmentioning

confidence: 99%

Lifespan estimation in marine turtles using genomic promoter CpG density

Mayne

Tucker²,

Berry

et al. 2020

PLoS ONE

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Maximum lifespan for most animal species is difficult to define. This is challenging for wildlife management as it is critical for estimating important aspects of population biology such as mortality rate, population viability, and period of reproductive potential. Recently, it has been shown cytosine-phosphate-guanine (CpG) density is predictive of maximum lifespan in vertebrates. This has made it possible to predict lifespan in long-lived species, which are generally the most intractable. In this study, we use gene promoter CpG density to predict the lifespan of five marine turtle species. Marine turtles are a particularly difficult group for lifespan estimation because of their migratory behaviour, longevity and high juvenile mortality rates, which all restrict individual tracking over their lifespan. Sanger sequencing was used to determine the CpG density in selected promoters. We predicted the lifespans for marine turtle species ranged from 50.4 years (flatback turtle, Natator depressus) to 90.4 years (leatherback turtle, Dermochelys coriacea). These lifespan predictions have broad applications in marine turtle research such as better understanding life cycles and determining population viability.

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The evolution of CpG density and lifespan in conserved primate and mammalian promoters

Cited by 25 publications

References 36 publications

A genomic predictor of lifespan in vertebrates

A genomic predictor of lifespan in vertebrates

Conservation of physiological dysregulation signatures of aging across primates

Lifespan estimation in marine turtles using genomic promoter CpG density

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