Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents

Horvath, Steve; Stein, Dan J.; Phillips, Nicole; Heany, Sarah J.; Kobor, Michæl S.; Lin, David; Myer, Landon; Zar, Heather J.; Levine, Andrew J.; Hoare, Jacqueline

doi:10.1097/qad.0000000000001854

Cited by 85 publications

(76 citation statements)

References 53 publications

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“…Tissue and organ samples from the National NeuroAIDS Tissue Consortium 52 . Blood samples from the Cape Town Adolescent Antiretroviral Cohort study 53 . Skin and other primary cells provided by Kenneth Raj 41 .…”

Section: Human Tissue Samplesmentioning

confidence: 99%

Reversing age: dual species measurement of epigenetic age with a single clock

Horvath

Singh

Raj

et al. 2020

Preprint

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Young blood plasma is known to confer beneficial effects on various organs in mice. However, it was not known whether young plasma rejuvenates cells and tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly-accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=593 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain-, liver-, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n=850 human tissue samples to the training data. We employed these six clocks to investigate the rejuvenation effects of a plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers and behavioral responses to assess cognitive functions. Cellular senescence, which is not associated with epigenetic aging, was also considerably reduced in vital organs. Overall, this study demonstrates that a plasma-derived treatment markedly reverses aging according to epigenetic clocks and benchmark biomarkers of aging.

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Section: Human Tissue Samplesmentioning

confidence: 99%

Reversing age: dual species measurement of epigenetic age with a single clock

Horvath

Singh

Raj

et al. 2020

Preprint

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“…We used these high quality DNAm data to construct different epigenetic clocks for vervet only and for both human and vervet. For the construction of the dual human-vervet clock, we used the DNAm data previously generated with the HorvathMammalMethylChip40 in 852 human samples representing 16 tissues from individuals 0 to 93 years old (Morgello et al 2001;Kabacik et al 2018;Horvath, Stein, et al 2018). Our clocks for vervet monkeys can be distinguished along three dimensions (tissue type, species, and measure of age).…”

Section: Epigenetic Clocksmentioning

confidence: 99%

“…We developed two dual species clocks based on our vervet samples and previously characterized human tissues (Morgello et al 2001;Horvath, Stein, et al 2018;Kabacik et al 2018). The human-vervet clock for chronological age (R=0.99 for the human and vervet samples and R=0.98 for the vervet samples, Figure 1E,F) and relative age (R=0.98 for the human and vervet samples and R=0.97 for the vervet samples, Figure 1G,H).…”

Section: Epigenetic Clocksmentioning

confidence: 99%

“…Tissue and organ samples were from the National NeuroAIDS Tissue Consortium (Morgello et al 2001). Blood samples were from the Cape Town Adolescent Antiretroviral Cohort study (Horvath, Stein, et al 2018). Skin and other primary cells were provided by Kenneth Raj (Kabacik et al 2018).…”

Section: Human Tissue Samplesmentioning

confidence: 99%

“…Because it is a natural host of simian immunodeficiency virus, which typically does not progress to immunodeficiency upon infection, the vervet is an established model for AIDS research (Pandrea et al 2006;Chahroudi et al 2012;Ma et al 2013;Ma et al 2014). Whereas HIV infection in humans is associated with age acceleration (Horvath, Stein, et al 2018;Horvath & Levine 2015), the links between the benign course of simian immunodeficiency virus infection and aging in the vervet remain unknown.…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic clock and methylation studies in vervet monkeys

Jasinska

Haghani²,

Zoller³

et al. 2020

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DNA methylation-based biomarkers of aging have been developed for many mammals but not yet for the vervet monkey (Chlorocebus sabaeus), which is a valuable non-human primate model for biomedical studies. We generated novel DNA methylation data from vervet cerebral cortex, blood, and liver using highly conserved mammalian CpGs represented on a custom array (HorvathMammalMethylChip40). We present six DNA methylation-based estimators of age: vervet multi-tissue epigenetic clock and tissue-specific clocks for brain cortex, blood, and liver. In addition, two dual species clocks (human-vervet clocks) for measuring chronological age and relative age, respectively. Relative age was defined as ratio of chronological age to maximum lifespan to address the species differences in maximum lifespan. The high accuracy of the human-vervet clocks demonstrates that epigenetic aging processes are evolutionary conserved in primates. When applying these vervet clocks to tissue samples from another primate species, rhesus macaque, we observed high age correlations but strong offsets. We characterized CpGs that correlate significantly with age in the vervet. CpG probes hypermethylated with age across tissues were located near the targets of Polycomb proteins SUZ12 and EED, and genes possessing the trimethylated H3K27 mark in their promoters.The epigenetic clocks are expected to be useful for age estimation of wild-born animals and anti-aging studies in vervets.

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