Ectopic resurrection of embryonic/developmental genes in aging

Liu, Zunpeng; Ji, Zhejun; Wang, Si; Zhang, Weiqi; Qu, Jing; Liu, Guang‐Hui

doi:10.1007/s44194-022-00013-y

Cited by 6 publications

(4 citation statements)

References 13 publications

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“…In various tissues, such as brain and lung, aging is characterized by the promiscuous re-activation of developmental programs, associated with a loss of repressive heterochromatin. 59 Notch is a key developmental pathway. 60 We found that Notch-related genes were aberrantly upregulated in SSPCs during aging, in conjunction with increased chromatin accessibility.…”

Section: Discussionmentioning

confidence: 99%

Loss of Notch signaling in skeletal stem cells enhances bone formation with aging

Remark,

Leclerc,

Ramsukh

et al. 2023

Bone Res

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Skeletal stem and progenitor cells (SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity. The molecular mechanisms that underlie this detrimental transformation are largely unknown. Single-cell RNA sequencing revealed that Notch signaling becomes elevated in SSPCs during aging. To examine the role of increased Notch activity, we deleted Nicastrin, an essential Notch pathway component, in SSPCs in vivo. Middle-aged conditional knockout mice displayed elevated SSPC osteo-lineage gene expression, increased trabecular bone mass, reduced bone marrow adiposity, and enhanced bone repair. Thus, Notch regulates SSPC cell fate decisions, and moderating Notch signaling ameliorates the skeletal aging phenotype, increasing bone mass even beyond that of young mice. Finally, we identified the transcription factor Ebf3 as a downstream mediator of Notch signaling in SSPCs that is dysregulated with aging, highlighting it as a promising therapeutic target to rejuvenate the aged skeleton.

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Section: Discussionmentioning

confidence: 99%

Loss of Notch signaling in skeletal stem cells enhances bone formation with aging

Remark,

Leclerc,

Ramsukh

et al. 2023

Bone Res

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“…The heterochromatin also becomes globally derepressed and more accessible in senescent cells, demonstrated by the loss of constitutive histone modifications (H3K9me3 and H4K20me3) and increased chromatin accessibility . The relaxed chromatin state segregates from the leakage expression of developmentally restricted genes (e.g., placenta-specific genes [PSGs]), as well as repetitive elements that are originally sealed in LADs (e.g., HERV and LINE1 elements) (De Cecco et al, 2013a;Deng et al, 2019;Liu et al, 2021e;Liu et al, 2022c;Liu et al, 2022d;Peng and Karpen, 2007). Although these elements are typically silenced in young cells, their derepression can trigger an IFN-I response and sterile inflammation, causally linked to cellular senescence, such as in human mesodermal cells (Bi et al, 2020;De Cecco et al, 2019).…”

Section: Epigenetic Changes During Agingmentioning

confidence: 99%

The landscape of aging

Cai

Song

et al. 2022

Sci. China Life Sci.

Self Cite

200

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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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“…Although we documented this effect for CD3+ and CD3-cells in the blood and between 5 different organs, this is likely a general phenomenon. This could be explained by the age-related erosion of epigenetic and chromatin landscape 44 which increases the noise in part through cell-to-cell variation in gene expression 97 , loss of lineage fidelity with age, and activation of lineage-inappropriate genes during aging [98][99][100][101][102] . Reactivation of human endogenous retroviruses during aging could also contribute to this process 103,104 .…”

Section: Image Reveals Heterogeneity Of In Vivo Reprogramming With Os...mentioning

confidence: 99%

Imaging-based chromatin and epigenetic age, ImAge, quantitates aging and rejuvenation.

terskikh,

Alvarez-Kuglen,

Rodriguez

et al. 2023

Preprint

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Biomarkers of biological age that predict the risk of disease and expected lifespan better than chronologi-cal age are key to efficient and cost-effective healthcare1–3. To advance a personalized approach to healthcare, such biomarkers must reliably and accurately capture individual biology, predict biological age, and provide scalable and cost-effective measurements. We developed a novel approach – image-based chromatin and epigenetic age (ImAge) that captures intrinsic progressions of biological age, which readily emerge as principal changes in the spatial organization of chromatin and epigenetic marks in single nuclei without regression on chronological age. ImAge captured the expected acceleration or deceleration of bio-logical age in mice treated with chemotherapy or following a caloric restriction regimen, respectively. Im-Age from chronologically identical mice inversely correlated with their locomotor activity (greater activity for younger ImAge), consistent with the widely accepted role of locomotion as an aging biomarker across species. Finally, we demonstrated that ImAge is reduced following transient expression of OSKM cassette in the liver and skeletal muscles and reveals heterogeneity of in vivo reprogramming. We propose that Im-Age represents the first-in-class imaging-based biomarker of aging with single-cell resolution.

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Ectopic resurrection of embryonic/developmental genes in aging

Cited by 6 publications

References 13 publications

Loss of Notch signaling in skeletal stem cells enhances bone formation with aging

Loss of Notch signaling in skeletal stem cells enhances bone formation with aging

The landscape of aging

Imaging-based chromatin and epigenetic age, ImAge, quantitates aging and rejuvenation.

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