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Depletion of SAM leading to loss of heterochromatin drives muscle stem cell ageing – Nature Metabolism

  • Benayoun, B. A., Pollina, E. A. & Brunet, A. Epigenetic regulation of ageing: linking environmental inputs to genomic stability. Nat. Rev. Mol. Cell Biol. 16, 593–610 (2015).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Villeponteau, B. The heterochromatin loss model of aging. Exp. Gerontol. 32, 383–394 (1997).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Ljungman, M. & Hanawalt, P. C. Efficient protection against oxidative DNA damage in chromatin. Mol. Carcinog. 5, 264–269 (1992).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Wood, J. G. & Helfand, S. L. Chromatin structure and transposable elements in organismal aging. Front. Genet. 4, 274 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Larson, K. et al. Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis. PLoS Genet. 8, e1002473 (2012).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Smeal, T., Claus, J., Kennedy, B., Cole, F. & Guarente, L. Loss of transcriptional silencing causes sterility in old mother cells of S. cerevisiae. Cell 84, 633–642 (1996).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Wasserzug-Pash, P. et al. Loss of heterochromatin and retrotransposon silencing as determinants in oocyte aging. Aging Cell 21, e13568 (2022).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Scaffidi, P. & Misteli, T. Lamin A-dependent nuclear defects in human aging. Science 312, 1059–1063 (2006).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Lee, J.-H., Kim, E. W., Croteau, D. L. & Bohr, V. A. Heterochromatin: an epigenetic point of view in aging. Exp. Mol. Med. 52, 1466–1474 (2020).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Bi, S. et al. SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer. Protein Cell 11, 483–504 (2020).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Liu, L. et al. Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist.Proc. Natl Acad. Sci. USA 118, e2025281118 (2021).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Liang, C. et al. Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration. Cell Res. 31, 187–205 (2021).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Berger, S. L. & Sassone-Corsi, P. Metabolic signaling to chromatin.Cold Spring Harb. Perspect. Biol. 8, a019463 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Su, X., Wellen, K. E. & Rabinowitz, J. D. Metabolic control of methylation and acetylation. Curr. Opin. Chem. Biol. 30, 52–60 (2016).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Chiang, P. K. et al. S-Adenosylmethionine and methylation. FASEB J. 10, 471–480 (1996).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Mews, P. et al. Acetyl-CoA synthetase regulates histone acetylation and hippocampal memory. Nature 546, 381–386 (2017).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Tsukada, Y. et al. Histone demethylation by a family of JmjC domain-containing proteins. Nature 439, 811–816 (2006).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Carey, B. W., Finley, L. W. S., Cross, J. R., Allis, C. D. & Thompson, C. B. Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature 518, 413–416 (2015).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Shiraki, N. et al. Methionine metabolism regulates maintenance and differentiation of human pluripotent stem cells. Cell Metab. 19, 780–794 (2014).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Yucel, N. et al. Glucose metabolism drives histone acetylation landscape transitions that dictate muscle stem cell function. Cell Rep. 27, 3939–3955 (2019).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Brunet, A., Goodell, M. A. & Rando, T. A. Ageing and rejuvenation of tissue stem cells and their niches. Nat. Rev. Mol. Cell Biol. 24, 45–62 (2023).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Goodell, M. A. & Rando, T. A. Stem cells and healthy aging. Science 350, 1199–1204 (2015).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Liu, B., Qu, J., Zhang, W., Izpisua Belmonte, J. C. & Liu, G.-H. A stem cell aging framework, from mechanisms to interventions. Cell Rep. 41, 111451 (2022).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Conboy, I. M. & Rando, T. A. Aging, stem cells and tissue regeneration: lessons from muscle. Cell Cycle 4, 407–410 (2005).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Liu, L. et al. Impaired Notch signaling leads to a decrease in p53 activity and mitotic catastrophe in aged muscle stem cells. Cell Stem Cell 23, 544–556 (2018).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Porpiglia, E. et al. Elevated CD47 is a hallmark of dysfunctional aged muscle stem cells that can be targeted to augment regeneration. Cell Stem Cell 29, 1653–1668 (2022).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Hernando-Herraez, I. et al. Ageing affects DNA methylation drift and transcriptional cell-to-cell variability in mouse muscle stem cells. Nat. Commun. 10, 4361 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, L. et al. Chromatin modifications as determinants of muscle stem cell quiescence and chronological aging. Cell Rep. 4, 189–204 (2013).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Zhang, X. et al. The loss of heterochromatin is associated with multiscale three-dimensional genome reorganization and aberrant transcription during cellular senescence. Genome Res. 31, 1121–1135 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Benjamin, D. I. et al. Multiomics reveals glutathione metabolism as a driver of bimodality during stem cell aging. Cell Metab. 35, 472–486 (2023).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Liu, F. et al. Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP. J. Med. Chem. 56, 8931–8942 (2013).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Greiner, D., Bonaldi, T., Eskeland, R., Roemer, E. & Imhof, A. Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3-9. Nat. Chem. Biol. 1, 143–145 (2005).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Kikuchi, H. & Sato, S. Fractionation of nonhistone proeins on a column of daunomycin-CH-Sepharose 4B. Biochim. Biophys. Acta 532, 113–121 (1978).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Haws, S. A. et al. Methyl-metabolite depletion elicits adaptive responses to support heterochromatin stability and epigenetic persistence. Mol. Cell 78, 210–223 (2020).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Ohtani, M. et al. Spermidine regulates insulin synthesis and cytoplasmic Ca2+ in mouse beta-TC6 insulinoma cells. Cell Struct. Funct. 34, 105–113 (2009).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Massaro, C., Thomas, J. & Phanstiel Iv, O. Investigation of polyamine metabolism and homeostasis in pancreatic cancers.Med. Sci. 5, 32 (2017).


    Google Scholar
     

  • Tabor, H. The protective effect of spermine and other polyamines against heat denaturation of deoxyribonucleic acid. Biochemistry 1, 496–501 (1962).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Eisenberg, T. et al. Induction of autophagy by spermidine promotes longevity. Nat. Cell Biol. 11, 1305–1314 (2009).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Agrimi, G. et al. Identification of the human mitochondrial S-adenosylmethionine transporter: bacterial expression, reconstitution, functional characterization and tissue distribution. Biochem. J. 379, 183–190 (2004).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Sun, Y. & Locasale, J. W. Rethinking the bioavailability and cellular transport properties of S-adenosylmethionine. Cell Stress 6, 1–5 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, S. E., Huskey, W. P., Borchardt, R. T. & Schowen, R. L. Chiral instability at sulfur of S-adenosylmethionine. Biochemistry 22, 2828–2832 (1983).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Albers, E. Metabolic characteristics and importance of the universal methionine salvage pathway recycling methionine from 5′-methylthioadenosine. IUBMB Life 61, 1132–1142 (2009).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Mentch, S. J. et al. Histone methylation dynamics and gene regulation occur through the sensing of one-carbon metabolism. Cell Metab. 22, 861–873 (2015).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Yu, W. et al. One-carbon metabolism supports S-adenosylmethionine and histone methylation to drive Inflammatory macrophages. Mol. Cell 75, 1147–1160 (2019).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Dai, Z., Mentch, S. J., Gao, X., Nichenametla, S. N. & Locasale, J. W. Methionine metabolism influences genomic architecture and gene expression through H3K4me3 peak width. Nat. Commun. 9, 1955 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sadhu, M. J. et al. Nutritional control of epigenetic processes in yeast and human cells. Genetics 195, 831–844 (2013).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Toraño, E. G., García, M. G., Fernández-Morera, J. L., Niño-García, P. & Fernández, A. F. The impact of external factors on the epigenome: in utero and over lifetime. BioMed. Res. Int. 2016, 2568635 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hyun, K., Jeon, J., Park, K. & Kim, J. Writing, erasing and reading histone lysine methylations. Exp. Mol. Med. 49, e324 (2017).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Pan, Y.-H. et al. The critical roles of polyamines in regulating ColE7 production and restricting ColE7 uptake of the colicin-producing Escherichia coli. J. Biol. Chem. 281, 13083–13091 (2006).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Rato, C., Amirova, S. R., Bates, D. G., Stansfield, I. & Wallace, H. M. Translational recoding as a feedback controller: systems approaches reveal polyamine-specific effects on the antizyme ribosomal frameshift. Nucleic Acids Res. 39, 4587–4597 (2011).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Wang, C. et al. Defining the molecular requirements for the selective delivery of polyamine conjugates into cells containing active polyamine transporters. J. Med. Chem. 46, 5129–5138 (2003).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Fan, J. et al. Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway. Oncotarget 8, 17475–17490 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Luchessi, A. D. et al. Involvement of eukaryotic translation initiation factor 5A (eIF5A) in skeletal muscle stem cell differentiation. J. Cell. Physiol. 218, 480–489 (2009).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Machado, L. et al. Tissue damage induces a conserved stress response that initiates quiescent muscle stem cell activation. Cell Stem Cell 28, 1125–1135 (2021).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Park, M. H. The post-translational synthesis of a polyamine-derived amino acid, hypusine, in the eukaryotic translation initiation factor 5A (eIF5A). J. Biochem. 139, 161–169 (2006).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Uchitomi, R. et al. Metabolomic analysis of skeletal muscle in aged mice. Sci. Rep. 9, 10425 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nishimura, K., Shiina, R., Kashiwagi, K. & Igarashi, K. Decrease in polyamines with aging and their ingestion from food and drink. J. Biochem. 139, 81–90 (2006).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Minois, N., Carmona-Gutierrez, D. & Madeo, F. Polyamines in aging and disease. Aging 3, 716–732 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Casero, R. A. Jr., Murray Stewart, T. & Pegg, A. E. Polyamine metabolism and cancer: treatments, challenges and opportunities. Nat. Rev. Cancer 18, 681–695 (2018).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Murray-Stewart, T. R., Woster, P. M. & Casero, R. A. Jr. Targeting polyamine metabolism for cancer therapy and prevention. Biochem. J. 473, 2937–2953 (2016).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Lewandowski, N. M. et al. Polyamine pathway contributes to the pathogenesis of Parkinson disease. Proc. Natl Acad. Sci. USA 107, 16970–16975 (2010).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Polis, B., Karasik, D. & Samson, A. O. Alzheimer’s disease as a chronic maladaptive polyamine stress response. Aging 13, 10770–10795 (2021).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Morrison, L. D., Becker, L., Ang, L. C. & Kish, S. J. Polyamines in human brain: regional distribution and influence of aging. J. Neurochem. 65, 636–642 (1995).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Graham, S. F. et al. Untargeted metabolomic analysis of human plasma indicates differentially affected polyamine and l-arginine metabolism in mild cognitive impairment subjects converting to Alzheimer’s disease. PLoS ONE 10, e0119452 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ost, M. et al. Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux. FASEB J. 29, 1314–1328 (2015).

    Article 
    PubMed 
    CAS 

    Google Scholar
     

  • Cosgrove, B. D. et al. Rejuvenation of the muscle stem cell population restores strength to injured aged muscles. Nat. Med. 20, 255–264 (2014).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Price, F. D. et al. Inhibition of JAK-STAT signaling stimulates adult satellite cell function. Nat. Med. 20, 1174–1181 (2014).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Liu, L., Cheung, T. H., Charville, G. W. & Rando, T. A. Isolation of skeletal muscle stem cells by fluorescence-activated cell sorting. Nat. Protoc. 10, 1612–1624 (2015).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Charville, G. W. et al. Ex vivo expansion and in vivo self-renewal of human muscle stem cells. Stem Cell Reports 5, 621–632 (2015).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Anders, S. & Huber, W. Differential expression analysis for sequence count data. Genome Biol. 11, R106 (2010).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

  • Brett, J. O. et al. Exercise rejuvenates quiescent skeletal muscle stem cells in old mice through restoration of Cyclin D1. Nat. Metab. 2, 307–317 (2020).

    Article 
    PubMed 
    PubMed Central 
    CAS 

    Google Scholar
     

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