Pan-primate studies of age and sex

Horvath, Steve; Haghani, Amin; Zoller, Joseph A.; Lu, Ake T.; Ernst, Jason; Pellegrini, Matteo; Jasinska, Anna J.; Mattison, Julie A.; Salmon, Adam B.; Raj, Ken; Horvath, Markus; Paul, Kimberly C.; Ritz, Beate; Robeck, Todd R.; Spriggs, Maria; Ehmke, Erin; Jenkins, Susan L.; Li, Cun; Nathanielsz, Peter W.

doi:10.1007/s11357-023-00878-3

Cited by 8 publications

(2 citation statements)

References 78 publications

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“…To build the human-rat clock, we analyzed previously generated methylation data from n = 1366 human tissue samples (adipose, blood, bone marrow, dermis, epidermis, heart, keratinocytes, fibroblasts, kidney, liver, lung, lymph node, muscle, pituitary, skin, spleen) from individuals whose ages ranged from 0 to 93. The data come from our study of primates [66]. Tissue and organ samples are from the National NeuroAIDS Tissue Consortium [67].…”

Section: Human Tissue Samplesmentioning

confidence: 99%

Reversal of biological age in multiple rat organs by young porcine plasma fraction

Horvath,

Singh,

Raj

et al. 2023

GeroScience

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Young blood plasma is known to confer beneficial effects on various organs in mice and rats. However, it was not known whether plasma from young adult pigs rejuvenates old rat 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 = 613 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 = 1366 human tissue samples to the training data. We employed these six rat clocks to investigate the rejuvenation effects of a porcine 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, behavioral responses encompassing cognitive functions. An immunoglobulin G (IgG) N-glycosylation pattern shift from pro- to anti-inflammatory also indicated reversal of glycan aging. Overall, this study demonstrates that a young porcine plasma-derived treatment markedly reverses aging in rats according to epigenetic clocks, IgG glycans, and other biomarkers of aging.

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Section: Human Tissue Samplesmentioning

confidence: 99%

Reversal of biological age in multiple rat organs by young porcine plasma fraction

Horvath,

Singh,

Raj

et al. 2023

GeroScience

Self Cite

View full text Add to dashboard Cite

show abstract

“…(1234567890) dermis, epidermis, heart, keratinocytes, fibroblasts, kidney, liver, lung, lymph node, muscle, pituitary, skin, spleen) from individuals whose ages ranged from 0 to 93. The data come from our study of primates [66]. Tissue and organ samples are from the National NeuroAIDS Tissue Consortium [67].…”

Section: Human Tissue Samplesmentioning

confidence: 99%

Reversal of Biological Age in Multiple Rat Organs by Young Porcine Plasma Fraction

Horvath,

Singh,

Raj

et al. 2023

Preprint

Self Cite

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Young blood plasma is known to confer beneficial effects on various organs in mice and rats. However, it was not known whether plasma from young pigs rejuvenates old rat 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=613 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=1366 human tissue samples to the training data. We employed these six rat clocks to investigate the rejuvenation effects of a porcine 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. An immunoglobulin G (IgG) N-glycosylation pattern shift from pro- to anti-inflammatory also indicated reversal of glycan aging. Overall, this study demonstrates that a young porcine plasma-derived treatment markedly reverses aging in rats according to epigenetic clocks, IgG glycans, and other biomarkers of aging.

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Cognitive rejuvenation in old rats by hippocampal OSKM gene therapy

Horvath,

Lacunza,

Mallat

et al. 2024

GeroScience

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Several studies have indicated that interrupted epigenetic reprogramming using Yamanaka transcription factors (OSKM) can rejuvenate cells from old laboratory animals and humans. However, the potential of OSKM-induced rejuvenation in brain tissue has been less explored. Here, we aimed to restore cognitive performance in 25.3-month-old female Sprague–Dawley rats using OSKM gene therapy for 39 days. Their progress was then compared with the cognitive performance of untreated 3.5-month-old rats as well as old control rats treated with a placebo adenovector. The Barnes maze test, used to assess cognitive performance, demonstrated enhanced cognitive abilities in old rats treated with OSKM compared to old control animals. In the treated old rats, there was a noticeable trend towards improved spatial memory relative to the old controls. Further, OSKM gene expression did not lead to any pathological alterations within the 39 days. Analysis of DNA methylation following OSKM treatment yielded three insights. First, epigenetic clocks for rats suggested a marginally significant epigenetic rejuvenation. Second, chromatin state analysis revealed that OSKM treatment rejuvenated the methylome of the hippocampus. Third, an epigenome-wide association analysis indicated that OSKM expression in the hippocampus of old rats partially reversed the age-related increase in methylation. In summary, the administration of Yamanaka genes via viral vectors rejuvenates the functional capabilities and the epigenetic landscape of the rat hippocampus.

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Pan-primate studies of age and sex

Cited by 8 publications

References 78 publications

Reversal of biological age in multiple rat organs by young porcine plasma fraction

Reversal of biological age in multiple rat organs by young porcine plasma fraction

Reversal of Biological Age in Multiple Rat Organs by Young Porcine Plasma Fraction

Cognitive rejuvenation in old rats by hippocampal OSKM gene therapy

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