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. 2022 Dec;17(12):1774-1785.
doi: 10.1080/15592294.2022.2080993. Epub 2022 Jun 2.

Epigenetic ageing of the prefrontal cortex and cerebellum in humans and chimpanzees

Elaine E Guevara  1   2   3 , William D Hopkins  4   5   6 , Patrick R Hof  7   8 , John J Ely  2   9 , Brenda J Bradley  2 , Chet C Sherwood  2
Affiliations

Epigenetic ageing of the prefrontal cortex and cerebellum in humans and chimpanzees

Elaine E Guevara et al. Epigenetics. 2022 Dec.

Abstract

Epigenetic age has emerged as an important biomarker of biological ageing. It has revealed that some tissues age faster than others, which is vital to understanding the complex phenomenon of ageing and developing effective interventions. Previous studies have demonstrated that humans exhibit heterogeneity in pace of epigenetic ageing among brain structures that are consistent with differences in structural and microanatomical deterioration. Here, we add comparative data on epigenetic brain ageing for chimpanzees, humans' closest relatives. Such comparisons can further our understanding of which aspects of human ageing are evolutionarily conserved or specific to our species, especially given that humans are distinguished by a long lifespan, large brain, and, potentially, more severe neurodegeneration with age. Specifically, we investigated epigenetic ageing of the dorsolateral prefrontal cortex and cerebellum, of humans and chimpanzees by generating genome-wide CpG methylation data and applying established epigenetic clock algorithms to produce estimates of biological age for these tissues. We found that both species exhibit relatively slow epigenetic ageing in the brain relative to blood. Between brain structures, humans show a faster rate of epigenetic ageing in the dorsolateral prefrontal cortex compared to the cerebellum, which is consistent with previous findings. Chimpanzees, in contrast, show comparable rates of epigenetic ageing in the two brain structures. Greater epigenetic change in the human dorsolateral prefrontal cortex compared to the cerebellum may reflect both the protracted development of this structure in humans and its greater age-related vulnerability to neurodegenerative pathology.

Keywords: Alzheimer‘s disease; Methylation; Pan troglodytes; ageing; development; neuroscience.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1.
Figure 1.
Life history stages are from [56]. Infancy is defined as birth until weaning, juvenility from weaning until menarche, adolescence from menarche until the onset of reproduction. Age at which 95% of adult brain size is attained from [57]. Age at peak reproduction is the peak proportion of females reproducing at this age and is from [58]. Chimpanzee estimate of age at first reproduction (AFR) is from wild populations and maximum lifespan (ML) estimates from captivity [44]. Human estimate of AFR based on compiled data from four contemporary hunter-gatherer groups (the Ache, Hadza, Hiwi, and!Kung) reported in [44]. Human ML (122) is also given in [44]. *Age at last reproduction is from [59]. The estimate of 39 for humans comes from the average age at last reproduction across three forager populations. Because most female chimpanzees die before reproductive senescence, these numbers are likely not equivalent for chimpanzees. [57], give an age at last birth of 42 for chimpanzees based on an average of maximum ages of last birth in four wild chimpanzee populations and 45 for humans, but which is based again on average age at last birth, not maximum. B.Brain regions analysed and dendrograms of hierarchical clustering based on full methylation data. Samples ending in ‘a’ are DLPFC samples and ending in ‘d’ are cerebellum samples. Sample numbers 1–8 are chimpanzee samples and sample numbers 19–24 and 26 are human samples. Chimpanzee and human brain figures taken from [60].
Figure 2.
Figure 2.
Epigenetic age estimates using the Horvath clock for humans and chimpanzees and results of the ANCOVA. A & B: Spearman’s rho is shown for each species (A = humans, B = chimpanzees) and region. C & D: Results of the ANCOVA comparing slopes of ageing for each region for (c) humans and (d) chimpanzees, along with the regression equations for each line. CB = cerebellum, DLPFC = dorsolateral prefrontal cortex.
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References

    1. Field AE, Robertson NA, Wang T, et al. DNA methylation clocks in aging: categories, causes, and consequences. Mol Cell. 2018;71:882–895. - PMC - PubMed
    1. Hannum G, Guinney J, Zhao L, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013;49:359–367. - PMC - PubMed
    1. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14:R115. - PMC - PubMed
    1. Binder AM, Corvalan C, Mericq V, et al. Faster ticking rate of the epigenetic clock is associated with faster pubertal development in girls. Epigenetics. 2018;13:85–94. - PMC - PubMed
    1. Chen BH, Marioni RE, Colicino E, et al. DNA methylation-based measures of biological age: meta-analysis predicting time to death. Aging. 8;2016:1844–1859. - PMC - PubMed

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