DNA methylation aging and transcriptomic studies in horses

Horvath, Steve; Haghani, Amin; Peng, Sichong; Hales, Erin N.; Zoller, Joseph A.; Raj, Ken; Larison, Brenda; Robeck, Todd R.; Petersen, Jessica L; Bellone, Rebecca; Finno, Carrie J.

doi:10.1038/s41467-021-27754-y

Cited by 37 publications

(24 citation statements)

References 65 publications

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“…These studies already demonstrate that one can build dual species epigenetic age estimators (e.g. human-naked mole rat clocks), which we refer to as third generation epigenetic clocks [9][10][11][12][13][14][15][16] , in contrast to first and second generation clocks that measure human age 4,18,19 and mortality risk 20,21 , respectively. However, it is not yet known whether one can develop a mathematical formula to estimate age in all mammalian species.…”

Section: Universal Pan-mammalian Epigenetic Clocksmentioning

confidence: 90%

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Universal DNA methylation age across mammalian tissues

Lu¹,

Fei²,

Haghani³

et al. 2021

Preprint

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Aging is often perceived as a degenerative process caused by random accrual of cellular damage over time. In spite of this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully developed for several different species, it is difficult to ignore the likelihood that a defined and shared mechanism instead, underlies the aging process. To address this, we generated 10,000 methylation arrays, each profiling up to 37,000 cytosines in highly-conserved stretches of DNA, from over 59 tissue-types derived from 128 mammalian species. From these, we identified and characterized specific cytosines, whose methylation levels change with age across mammalian species. Genes associated with these cytosines are greatly enriched in mammalian developmental processes and implicated in age-associated diseases. From the methylation profiles of these age-related cytosines, we successfully constructed three highly accurate universal mammalian clocks for eutherians, and one universal clock for marsupials. The universal clocks for eutherians are similarly accurate for estimating ages (r>0.96) of any mammalian species and tissue with a single mathematical formula. Collectively, these new observations support the notion that aging is indeed evolutionarily conserved and coupled to developmental processes across all mammalian species - a notion that was long-debated without the benefit of this new and compelling evidence.

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Section: Universal Pan-mammalian Epigenetic Clocksmentioning

confidence: 90%

“…In separate articles, we described the application of the mammalian methylation array to individual mammalian species [9][10][11][12][13][14][15][16][17] . These studies already demonstrate that one can build dual species epigenetic age estimators (e.g.…”

Section: Universal Pan-mammalian Epigenetic Clocksmentioning

confidence: 99%

Universal DNA methylation age across mammalian tissues

Lu¹,

Fei²,

Haghani³

et al. 2021

Preprint

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“…We could not evaluate whether cytosines affect gene expression levels in opossums. However, we recently studied the relationship between cytosine methylation and gene expression levels in horses [ 62 ].…”

Section: Resultsmentioning

confidence: 99%

Epigenetic clock and methylation studies in marsupials: opossums, Tasmanian devils, kangaroos, and wallabies

et al. 2022

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The opossum (Monodelphis domestica), with its sequenced genome, ease of laboratory care and experimental manipulation, and unique biology, is the most used laboratory marsupial. Using the mammalian methylation array, we generated DNA methylation data from n = 100 opossum samples from the ear, liver, and tail. We contrasted postnatal development and later aging effects in the opossum methylome with those in mouse (Mus musculus, C57BL/6 J strain) and other marsupial species such as Tasmanian devil, kangaroos, and wallabies. While the opossum methylome is similar to that of mouse during postnatal development, it is distinct from that shared by other mammals when it comes to the age-related gain of methylation at target sites of polycomb repressive complex 2. Our immunohistochemical staining results provide additional support for the hypothesis that PRC2 activity increases with later aging in mouse tissues but remains constant in opossum tissues. We present several epigenetic clocks for opossums that are distinguished by their compatibility with tissue type (pan-tissue and blood clock) and species (opossum and human). Two dual-species human-opossum pan-tissue clocks accurately measure chronological age and relative age, respectively. The human-opossum epigenetic clocks are expected to provide a significant boost to the attractiveness of opossum as a biological model. Additional epigenetic clocks for Tasmanian devil, red kangaroos and other species of the genus Macropus may aid species conservation efforts.

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“…DNA methylation is a dynamic process that is carried out by DNA methyltransferases (DNMTs) and was recently recognized as a biomarker for biological age (Noroozi et al, 2021). "Epigenetic clocks" are based on the methylation levels of certain CpG sites (Horvath et al, 2022) and these DNA methylation-based age estimators help measure the cumulative effects of epigenetic drift on aging across a broad spectrum of human tissues and cell types (Horvath, 2013). Significant changes to histone processes, particularly in histone methylation and acetylation, are also frequently observed in senescent cells.…”

Section: Epigenetic Changes During Agingmentioning

confidence: 99%

The landscape of aging

Cai

Song

et al. 2022

Sci. China Life Sci.

132

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Aging is characterized by a progressive deterioration of physiological integrity, leading to impaired functional ability and ultimately increased susceptibility to death. It is a major risk factor for chronic human diseases, including cardiovascular disease, diabetes, neurological degeneration, and cancer. Therefore, the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences. In recent years, there has been unprecedented progress in aging research, particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes. In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases, we review the descriptive, conceptual, and interventive aspects of the landscape of aging composed of a number of layers at the cellular, tissue, organ, organ system, and organismal levels.

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DNA methylation aging and transcriptomic studies in horses

Cited by 37 publications

References 65 publications

Universal DNA methylation age across mammalian tissues

Universal DNA methylation age across mammalian tissues

Epigenetic clock and methylation studies in marsupials: opossums, Tasmanian devils, kangaroos, and wallabies

The landscape of aging

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