Epigenetic aging of human hematopoietic cells is not accelerated upon transplantation into mice

Frobel, Joana; Rahmig, Susann; Franzen, Julia; Waskow, Claudia; Wagner, Wolfgang

doi:10.1186/s13148-018-0499-7

Cited by 13 publications

(8 citation statements)

References 25 publications

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“…In analogy to the age-associated DNA methylation patterns, the epigenetic modifications during replicative senescence are also reset during reprogramming into induced pluripotent stem cells [74]. In regard to the cellular niche, human hematopoietic cells do not exhibit epigenetic age acceleration upon transplantation into a faster aging species, the mouse [75]. Similarly, the DNA methylation age measurement from hematopoietic stem cell transfusion matches the age of the donor and not that of an older recipient [76, 77].…”

Section: Challengementioning

confidence: 99%

DNA methylation aging clocks: challenges and recommendations

et al. 2019

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Epigenetic clocks comprise a set of CpG sites whose DNA methylation levels measure subject age. These clocks are acknowledged as a highly accurate molecular correlate of chronological age in humans and other vertebrates. Also, extensive research is aimed at their potential to quantify biological aging rates and test longevity or rejuvenating interventions. Here, we discuss key challenges to understand clock mechanisms and biomarker utility. This requires dissecting the drivers and regulators of age-related changes in single-cell, tissue- and disease-specific models, as well as exploring other epigenomic marks, longitudinal and diverse population studies, and non-human models. We also highlight important ethical issues in forensic age determination and predicting the trajectory of biological aging in an individual.

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Section: Challengementioning

confidence: 99%

DNA methylation aging clocks: challenges and recommendations

et al. 2019

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“…Recently, Frobel et al (2018) reported an interesting use of the epigenetic clock in determining the effect of the tissue micro-environment on the cellular aging of human hematopoietic stem cells. They used the Horvath and Hannum clocks to determine whether human stem cells transplanted into mice showed an increased rate of epigenetic aging because of the accelerated aging environment of the mouse.…”

Section: Epigenetic Clocksmentioning

confidence: 99%

The role of DNA methylation in epigenetics of aging

Unnikrishnan

Freeman

Jackson

et al. 2019

Pharmacology & Therapeutics

234

158

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Recent research suggests that epigenetics, especially DNA methylation, plays a mechanistic role in aging. Epigenetic clocks, which measure changes in a few hundred specific CpG sites, can accurately predict chronological age in a variety of species, including humans. These clocks are currently the bestbiomarkers for predicting mortality in humans. Additionally, several studies have characterized the effects of aging across the methylome in a wide variety of tissues from humans and mice. A small fraction (~2%) of the CpG sites show age-related changes, either hypermethylation or hypomethylation with aging. Evaluation of non-CpG site methylation has only been examined in a few studies, with about ~0.5% of these sites showing achange with age. Therefore, while only a small fraction of cytosines in the genome show changes in DNA methylation with age, this represents 2 to 3 million cytosines in the genome. Importantly, the only study to compare the effect of aging on DNA methylation in male and female mice and humans found that N95% of the age-related changes in DNA methylation in the hippocampus were sexually divergent, i.e., the methylation did not differ between males and females atyoung age but age-related changes occurred in one sex but not the other. The age-related changes in DNA methylation tend to be enriched and under-represented in specific genomic contexts, with some commonalities between tissues and species that require further investigation. The strongest evidence that the age-related changes in DNA methylation play a role in aging comes from studies of anti-aging interventions (e.g., caloric restriction, dwarfism, and rapamycin treatment) in mice. These anti-aging interventions deaccelerate the epigenetic clocks and reverse/prevent 20 to 40% of the age-related changes in DNA methylation. It will be important in the future to demonstrate that at least some of the age-related changes in DNA methylation directly lead to alterations in the transcriptome of cells/tissues that could potentially contribute to aging.

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“…Importantly, hematopoietic stem cell transplantation patients have shown that the recipient’s blood cells continue to reflect the DNAm age of the donor despite large differences between donor and recipient ages, indicating that DNAm clock age is a cell-intrinsic property [ 57 ]. Remarkably, a lack of age acceleration in human hematopoietic cells that are transplanted into mice provides further evidence for a cell-intrinsic DNAm clock [ 58 ]. Many other DNAm clocks have been developed since the initial multi-tissue clock, including a clock for mouse tissues [ 59 ] as well as for cells in culture [ 60 ].…”

Section: Nature Of Somatic Cellular Clocks: Epigenetic (Dnam) Clockmentioning

confidence: 99%

No Time to Age: Uncoupling Aging from Chronological Time

LaRocca¹,

Lee²,

West³

et al. 2021

Genes

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Multicellular life evolved from simple unicellular organisms that could replicate indefinitely, being essentially ageless. At this point, life split into two fundamentally different cell types: the immortal germline representing an unbroken lineage of cell division with no intrinsic endpoint and the mortal soma, which ages and dies. In this review, we describe the germline as clock-free and the soma as clock-bound and discuss aging with respect to three DNA-based cellular clocks (telomeric, DNA methylation, and transposable element). The ticking of these clocks corresponds to the stepwise progressive limitation of growth and regeneration of somatic cells that we term somatic restriction. Somatic restriction acts in opposition to strategies that ensure continued germline replication and regeneration. We thus consider the plasticity of aging as a process not fixed to the pace of chronological time but one that can speed up or slow down depending on the rate of intrinsic cellular clocks. We further describe how germline factor reprogramming might be used to slow the rate of aging and potentially reverse it by causing the clocks to tick backward. Therefore, reprogramming may eventually lead to therapeutic strategies to treat degenerative diseases by altering aging itself, the one condition common to us all.

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Epigenetic aging of human hematopoietic cells is not accelerated upon transplantation into mice

Cited by 13 publications

References 25 publications

DNA methylation aging clocks: challenges and recommendations

DNA methylation aging clocks: challenges and recommendations

The role of DNA methylation in epigenetics of aging

No Time to Age: Uncoupling Aging from Chronological Time

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