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Elevated Histone Expression Promotes Life Span Extension
Open accessAbstract
Changes to the chromatin structure accompany aging, but the molecular mechanisms underlying aging and the accompanying changes to the chromatin are unclear. Here, we report a mechanism whereby altering chromatin structure regulates life span. We show that normal aging is accompanied by a profound loss of histone proteins from the genome. Indeed, yeast lacking the histone chaperone Asf1 or acetylation of histone H3 on lysine 56 are short lived, and this appears to be at least partly due to their having decreased histone levels. Conversely, increasing the histone supply by inactivation of the histone information regulator (Hir) complex or overexpression of histones dramatically extends life span via a pathway that is distinct from previously known pathways of life span extension. This study indicates that maintenance of the fundamental chromatin structure is critical for slowing down the aging process and reveals that increasing the histone supply extends life span.
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“Overexpression of SIR2, histones, or deletion of the histone methyltransferase gene SET2, extends yeast lifespan, indicating that epigenetic changes are not merely a biomarker, but a cause of yeast aging (Dang et al., 2009; Feser et al., 2010; Hu et al., 2014; Kaeberlein et al., 1999; Ryu et al., 2014).”
From Loss of epigenetic information as a cause of mammalian aging (2023) · cites this paper as Feser et al., 2010
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“Nucleosome occupancy can decrease with age (Figure 2), and ameliorating this loss in yeast increases lifespan (Feser et al., 2010; Hu et al., 2014; Ivanov et al., 2013).”
From The Aging Epigenome (2016) · cites this paper as Feser et al., 2010
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Metadata
- Authors
- Feser, J., Truong, D., Das, C., Carson, J. J., Kieft, J., Harkness, T., & Tyler, J. K.
- Affiliations
- University of Colorado Anschutz (US)
- Howard Hughes Medical Institute (US)
- University of Saskatchewan (CA)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Tyler, Jessica K.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 39
- Issue
- 5
- Pages
- 724-735
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3966075
- OpenAlex
- W1990955843
- Cited by
- 435
- References
- 62
- Citations by year
- 2026: 8 · 2025: 22 · 2024: 21 · 2023: 29 · 2022: 19 · 2021: 48 · 2020: 33 · 2019: 27 · 2018: 36 · 2017: 23 · 2016: 28 · 2015: 32 · 2014: 25 · 2013: 30 · 2012: 25
- FWCI
- 8.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Cancer Center, University of Colorado
- National Cancer Institute (R01CA095641)
- National Institute of General Medical Sciences (GM64475, R01GM064475, T32-GM08370)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- histone expression, lifespan extension, aging, chromatin structure, histone H3 lysine 56 acetylation, yeast
- MeSH terms
- Chromatin, Histones, Saccharomyces cerevisiae, Gene Expression Regulation, Fungal, Saccharomyces cerevisiae Proteins
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