A genomic predictor of lifespan in vertebrates

Mayne, Benjamin; Berry, Oliver; Davies, Campbell R.; Farley, Jessica; Jarman, Simon

doi:10.1038/s41598-019-54447-w

Cited by 55 publications

(39 citation statements)

References 82 publications

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“…Conversely, DNAm often increases (i.e., shows hypermethylation) at CpG islands, which are as other vertebrates 28 , but the genes involved were not enriched for any pathway or biological process.…”

Section: Introductionmentioning

confidence: 88%

Genome Methylation Predicts Age and Longevity of Bats

Wilkinson

Adams

Arnold

et al. 2020

Preprint

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Bats hold considerable potential for understanding exceptional longevity because some species can live eight times longer than other mammals of similar size [1]. Estimating their age or longevity is difficult because they show few signs of aging. DNA methylation (DNAm) provides a potential solution given its utility for estimating age [2-4] and lifespan [5-7] in humans. Here, we profile DNAm from wing biopsies of nearly 700 individuals representing 26 bat species and demonstrate that DNAm can predict chronological age accurately. Furthermore, the rate DNAm changes at age-informative sites is negatively related to longevity. To identify longevity-informative sites, we compared DNAm rates between three long-lived and two short-lived species. Hypermethylated age and longevity sites are enriched for histone and chromatin features associated with transcriptional regulation and preferentially located in the promoter regions of helix-turn-helix transcription factors (TFs). Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results, in part, from augmented immune response and cancer suppression.

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Section: Introductionmentioning

confidence: 88%

Genome Methylation Predicts Age and Longevity of Bats

Wilkinson

Adams

Arnold

et al. 2020

Preprint

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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 prediction was determined using the model developed previously that is exclusive to five vertebrate classes [12]. Lifespan prediction is conducted by determining the CpG density within selected genomic promoters.…”

Section: Predicting Lifespanmentioning

confidence: 99%

“…In this study, sanger sequencing was used to determine CpG density thereby removing the possibility of a lack of coverage. Lifespan prediction from DNA has shown to be highly predictive across most speciose vertebrate classes, including reptilia [12]. In the absence of robust observational information on the lifespans of wild marine turtles, molecular predictions represent useful consistently derived foundation values for this iconic and vulnerable group of marine animals.…”

Section: Plos Onementioning

confidence: 99%

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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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“…Bowhead whales ( Balaena mysticetus ) are unusually long‐lived species of baleen whale (George et al, 1999, in press; Mayne, Berry, Davies, Farley, & Jarman, 2019; Seim et al, 2014; Tacutu et al, 2012). Although the skeletal anatomy of bowheads is well‐described (Eschricht & Reinhardt, 1866), the molecular signals underlying bone phenotypes mostly remain at best inferred based on gene expression and protein signaling studies from other aquatic taxa.…”

Section: Introductionmentioning

confidence: 99%

Linking gene expression and phenotypic changes in the developmental and evolutionary origins of osteosclerosis in the ribs of bowhead whales (Balaena mysticetus)

et al. 2020

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Bowhead whales are among the longest-lived mammals with an extreme lifespan of about 211 years. During the first 25 years of their lives, rib bones increase in mineral density and the medulla transitions from compact to trabecular bone. Molecular drivers associated with these phenotypic changes in bone remain unknown. This study assessed expression levels of osteogenic genes from samples of rib bones of bowheads. Samples were harvested from prenatal to 86-year-old whales, representing the first third of the bowhead lifespan. Fetal to 2-year-old bowheads showed expression levels consistent with the rapid deposition of the bone extracellular matrix. Sexually mature animals showed expression levels associated with low rates of osteogenesis and increased osteoclastogenesis. After the first 25 years of life, declines in osteogenesis corresponded with increased expression of EZH2, an epigenetic regulator of osteogenesis. These findings suggest EZH2 may be at least one epigenetic modifier that contributes to the age-related changes in the rib bone phenotype along with the transition from compact to trabecular bone. Ancient cetaceans and their fossil relatives also display these phenotypes, suggesting EZH2 may have shaped the skeleton of whales in evolutionary history.

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A genomic predictor of lifespan in vertebrates

Cited by 55 publications

References 82 publications

Genome Methylation Predicts Age and Longevity of Bats

Genome Methylation Predicts Age and Longevity of Bats

Lifespan estimation in marine turtles using genomic promoter CpG density

Linking gene expression and phenotypic changes in the developmental and evolutionary origins of osteosclerosis in the ribs of bowhead whales (Balaena mysticetus)

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