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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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Citations
Cites
Crystal structure of the nucleosome core particle at 2.8 Å resolution
Luger, K., Mäder, A. W., Richmond, R. K., Sargent, D. F., & Richmond, T. J. (1997) · Nature · doi:10.1038/38444 · Cited by 9,466
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
Imai, S.-I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000) · Nature · doi:10.1038/35001622 · Cited by 3,510
The Role of Chromatin during Transcription
Li, B., Carey, M., & Workman, J. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.015 · Cited by 3,503
Kaeberlein, M., McVey, M., & Guarente, L. (1999) · Genes & Development · doi:10.1101/gad.13.19.2570 · Cited by 2,253 · cited 9×
“Collectively, these data indicate that extra histone supply is unlikely to extend life span via the identical pathways by which ERC accumulation and Sir2 influence life span. ram (aged) from strain UCC5181 were subject to ChIP analysis for histone H3 pendent experiments, whose results are shown individually in Figures…”
BackgroundInfluentialHistone H4-K16 Acetylation Controls Chromatin Structure and Protein Interactions
Shogren‐Knaak, M. A., Ishii, H., Sun, J.-M., Pazin, M. J., Davie, J., & Peterson, C. L. (2006) · Science · doi:10.1126/science.1124000 · Cited by 1,959
Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients
Kaeberlein, M., Powers, R. W., Steffen, K. K., Westman, E. A., Hu, D., Dang, N., Kerr, E. O., Kirkland, K. T., Fields, S., & Kennedy, B. K. (2005) · Science · doi:10.1126/science.1115535 · Cited by 1,293
Chromatin Challenges during DNA Replication and Repair
Groth, A., Rocha, W., Verreault, A., & Almouzni, G. (2007) · Cell · doi:10.1016/j.cell.2007.01.030 · Cited by 733
DNA methylation and histone modifications: teaming up to silence genes
Fuks, F. (2005) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2005.08.002 · Cited by 669
Histone H4 lysine 16 acetylation regulates cellular lifespan
Dang, W., Steffen, K. K., Perry, R., Dorsey, J. A., Johnson, F. B., Shilatifard, A., Kaeberlein, M., Kennedy, B. K., & Berger, S. L. (2009) · Nature · doi:10.1038/nature08085 · Cited by 667
The RCAF complex mediates chromatin assembly during DNA replication and repair
Tyler, J. K., Adams, C. R., Chen, S.-R., Kobayashi, R., Kamakaka, R. T., & Kadonaga, J. T. (1999) · Nature · doi:10.1038/990147 · Cited by 555
Self-citationGottlieb, S., & Esposito, R. E. (1989) · Cell · doi:10.1016/0092-8674(89)90681-8 · Cited by 543
Yeast Life Span Extension by Depletion of 60S Ribosomal Subunits Is Mediated by Gcn4
Steffen, K. K., MacKay, V. L., Kerr, E. O., Tsuchiya, M., Hu, D., Fox, L. A., Dang, N., Johnston, E. D., Oakes, J. A., Tchao, B. N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.02.037 · Cited by 465
Identification of High-Copy Disruptors of Telomeric Silencing in Saccharomyces cerevisiae
Singer, M. S., Kahana, A., Wolf, A. J., Meisinger, L. L., Peterson, S. E., Goggin, C., Mahowald, M., & Gottschling, D. E. (1998) · Genetics · doi:10.1093/genetics/150.2.613 · Cited by 463
Acetylation of Histone H3 Lysine 56 Regulates Replication-Coupled Nucleosome Assembly
Li, Q., Zhou, H., Wurtele, H., Davies, B., Horazdovsky, B., Verreault, A., & Zhang, Z. (2008) · Cell · doi:10.1016/j.cell.2008.06.018 · Cited by 447 · cited 1×
“This may reflect a defect in chromatin assembly in the absence of Rtt109 and Asf1 (Li et al., 2008).”
BackgroundChen, C., Carson, J. J., Feser, J., Tamburini, B. A. J., Zabaronick, S., Linger, J. G., & Tyler, J. K. (2008) · Cell · doi:10.1016/j.cell.2008.06.035 · Cited by 426
Self-citationRtt109 Acetylates Histone H3 Lysine 56 and Functions in DNA Replication
Han, J., Zhou, H., Horazdovsky, B. F., Zhang, K., Xu, R.-M., & Zhang, Z. (2007) · Science · doi:10.1126/science.1133234 · Cited by 421
Genomewide studies of histone deacetylase function in yeast
Bernstein, B., Tong, J. K., & Schreiber, S. L. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.250477697 · Cited by 419
A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans
Rea, S. L., Wu, D., Cypser, J. R., Vaupel, J. W., & Johnson, T. E. (2005) · Nature Genetics · doi:10.1038/ng1608 · Cited by 414
Elimination of Replication Block Protein Fob1 Extends the Life Span of Yeast Mother Cells
Defossez, P., Prusty, R., Kaeberlein, M. R., Lin, S.-J., Ferrigno, P. K., Silver, P. A., Keil, R., & Guarente, L. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80472-4 · Cited by 401
Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast
Wyrick, J. J., Holstege, F. C. P., Jennings, E. G., Causton, H. C., Shore, D., Grunstein, M. R., Lander, E. S., & Young, R. A. (1999) · Nature · doi:10.1038/46567 · Cited by 394
Acetylation in Histone H3 Globular Domain Regulates Gene Expression in Yeast
Xu, F., Zhang, K., & Grunstein, M. R. (2005) · Cell · doi:10.1016/j.cell.2005.03.011 · Cited by 394
Kaufman, P. D., Kobayashi, R., & Stillman, B. (1997) · Genes & Development · doi:10.1101/gad.11.3.345 · Cited by 380
Daughter cells of Saccharomyces cerevisiae from old mothers display a reduced life span.
Kennedy, B. K., Austriaco, N. P. G., & Guarente, L. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.127.6.1985 · Cited by 305
Replicative Aging in Yeast: The Means to the End
Steinkraus, K. A., Kaeberlein, M. R., & Kennedy, B. K. (2008) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.23.090506.123509 · Cited by 282
Longevity Regulation by Drosophila Rpd3 Deacetylase and Caloric Restriction
Rogina, B., Helfand, S. L., & Frankel, S. A. (2002) · Science · doi:10.1126/science.1078986 · Cited by 276
Frei, C., & Gasser, S. M. (2000) · Genes & Development · doi:10.1101/gad.14.1.81 · Cited by 264
Cell Cycle and Checkpoint Regulation of Histone H3 K56 Acetylation by Hst3 and Hst4
Maas, N. L., Miller, K. M., DeFazio, L. G., & Toczyski, D. P. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.06.006 · Cited by 237
Williams, S. K., Truong, D. M., & Tyler, J. K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800057105 · Cited by 229
Self-citationHST2 Mediates SIR2 -Independent Life-Span Extension by Calorie Restriction
Lamming, D. W., Latorre‐Esteves, M., Medvedik, O., Wong, S. N., Tsang, F. A., Wang, C., Lin, S.-J., & Sinclair, D. A. (2005) · Science · doi:10.1126/science.1113611 · Cited by 227
Replication-Independent Histone Deposition by the HIR Complex and Asf1
Green, E. M., Antczak, A. J., Bailey, A. O., Franco, A. A., Wu, K. J., Yates, J. R., & Kaufman, P. D. (2005) · Current Biology · doi:10.1016/j.cub.2005.10.053 · Cited by 227
Smith, J. S., Caputo, E. M., & Boeke, J. D. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.4.3184 · Cited by 225
Modulation of Life-span by Histone Deacetylase Genes inSaccharomyces cerevisiae
Kim, S., Benguría, A., Lai, C.-Y., & Jazwinski, S. M. (1999) · Molecular Biology of the Cell · doi:10.1091/mbc.10.10.3125 · Cited by 212
Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans
McColl, G., Killilea, D. W., Hubbard, A. E., Vantipalli, M. C., Melov, S., & Lithgow, G. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m705028200 · Cited by 202
Quantitative evidence for conserved longevity pathways between divergent eukaryotic speciesPreprint
Smith, E. D., Tsuchiya, M., Fox, L. A., Dang, N., Hu, D., Kerr, E. O., Johnston, E. D., Tchao, B. N., Pak, D. N., Welton, K. L., et al. (2008) · Genome Research · doi:10.1101/gr.074724.107 · Cited by 200
Lindstrom, D. L., & Gottschling, D. E. (2009) · Genetics · doi:10.1534/genetics.109.106229 · Cited by 197
Lin, S., Manchester, J. K., & Gordon, J. I. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103509200 · Cited by 188
Chaperone Control of the Activity and Specificity of the Histone H3 Acetyltransferase Rtt109
Fillingham, J., Recht, J., Silva, A. C., Suter, B., Emili, A., Štagljar, I., Krogan, N. J., Allis, C. D., Keogh, M., & Greenblatt, J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00182-08 · Cited by 188
Han, J., Zhou, H., Li, Z., Xu, R.-M., & Zhang, Z. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702496200 · Cited by 182
Kaufman, P. D., Cohen, J. L., & Osley, M. A. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.8.4793 · Cited by 168
Sir2 Deacetylates Histone H3 Lysine 56 to Regulate Telomeric Heterochromatin Structure in Yeast
Xu, F., Zhang, Q., Zhang, K., Xie, W., & Grunstein, M. R. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.07.021 · Cited by 161
DNA methylation in aging of mice
Singhal, R. P., Mays-Hoopes, L. L., & Eichhorn, G. L. (1987) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(87)90040-6 · Cited by 161
Enzymatic activities of Sir2 and chromatin silencing
Moazed, D. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00202-7 · Cited by 160
Yeast ASF1 Protein Is Required for Cell Cycle Regulation of Histone Gene Transcription
Sutton, A., Bucaria, J., Osley, M. A., & Sternglanz, R. (2001) · Genetics · doi:10.1093/genetics/158.2.587 · Cited by 150
Myung, K., Pennaneach, V., Kats, E. S., & Kolodner, R. D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1232239100 · Cited by 140
Spector, M. S., Raff, A. C., DeSilva, H., Lee, K. M. L., & Osley, M. A. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.2.545 · Cited by 135
Genome instability, cancer and aging
Maslov, A. Y., & Vijg, J. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.03.020 · Cited by 134
Sirtuin‐independent effects of nicotinamide on lifespan extension from calorie restriction in yeast
Tsuchiya, M., Dang, N., Kerr, E. O., Hu, D., Steffen, K. K., Oakes, J. A., Kennedy, B. K., & Kaeberlein, M. R. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00240.x · Cited by 117
Mrc1 and Srs2 are major actors in the regulation of spontaneous crossover
Robert, T., Ravault, D., Fabre, F., & Gangloff, S. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601158 · Cited by 107
Ramey, C. J., Howar, S. R., Adkins, M. W., Linger, J. G., Spicer, J., & Tyler, J. K. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.23.10313-10327.2004 · Cited by 99
Self-citationAdkins, M. W., Carson, J. J., English, C. M., Ramey, C. J., & Tyler, J. K. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608025200 · Cited by 91
Self-citationBarger, J. L., Kayo, T., Pugh, T. D., Prolla, T. A., & Weindruch, R. H. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2008.06.013 · Cited by 90
Effect of Replicative Age on Transcriptional Silencing Near Telomeres inSaccharomyces cerevisiae
Kim, S., Villeponteau, B., & Jazwinski, S. M. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0240 · Cited by 73
Mays-Hoopes, L. L., Brown, A., & Huang, R. C. C. (1983) · Molecular and Cellular Biology · doi:10.1128/mcb.3.8.1371 · Cited by 65
Genome-wide identification of conserved longevity genes in yeast and worms
Smith, E. D., Kennedy, B. K., & Kaeberlein, M. R. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.017 · Cited by 62
Transcriptional instability is not a universal attribute of aging
Warren, L. A., Rossi, D. J., Schiebinger, G. R., Weissman, I. L., Kim, S. K., & Quake, S. R. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00337.x · Cited by 56
Systems biology of aging in four species
Zahn, J. M., & Kim, S. K. (2007) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2007.07.004 · Cited by 56
Zabaronick, S., & Tyler, J. K. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.2.652-660.2005 · Cited by 53
Self-citationGenome dynamics and transcriptional deregulation in aging
Busuttil, R. A., Bahar, R., & Vijg, J. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.09.060 · Cited by 49
Pathways Change in Expression During Replicative Aging in Saccharomyces cerevisiae
Yiu, G., McCord, A., Wise, A., Jindal, R., Hardee, J. J., Kuo, A., Shimogawa, M. M., Cahoon, L. A., Wu, M., Kloke, J., et al. (2008) · The Journals of Gerontology Series A · doi:10.1093/gerona/63.1.21 · Cited by 49
Drosophila longevity is not affected by heterochromatin‐mediated gene silencing
Frankel, S. A., & Rogina, B. (2005) · Aging Cell · doi:10.1111/j.1474-9726.2005.00143.x · Cited by 17
The HIR4-1 mutation defines a new class of histone regulatory genes in Saccharomyces cerevisiae.
Spector, M. S., & Osley, M. A. (1993) · Genetics · doi:10.1093/genetics/135.1.25 · Cited by 17
Sequence Analysis of 203 Kilobases from Saccharomyces cerevisiae Chromosome VII
Rieger, M. A., Brückner, M., Schäfer, M., & Müller-Auer, S. (1997) · Yeast · doi:10.1002/(sici)1097-0061(19970915)13:11 · Cited by 5
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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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