Global heterochromatin loss: a unifying theory of aging? - PubMed (original) (raw)

Global heterochromatin loss: a unifying theory of aging?

Amy Tsurumi et al. Epigenetics. 2012 Jul.

Abstract

The aging field is replete with theories. Over the past years, many distinct, yet overlapping mechanisms have been proposed to explain organismal aging. These include free radicals, loss of heterochromatin, genetically programmed senescence, telomere shortening, genomic instability, nutritional intake and growth signaling, to name a few. The objective of this Point-of-View is to highlight recent progress on the "loss of heterochromatin" model of aging and to propose that epigenetic changes contributing to global heterochromatin loss may underlie the various cellular processes associated with aging.

PubMed Disclaimer

Figures

None

Figure 1. Heterochromatin redistribution during aging. Aging is associated with a loss of constitutive heterochromatin, as demonstrated by a decrease in H3K9 methylation and delocalization of HP1 proteins. Concurrently, increases in facultative heterochromatin occur at specific loci, particularly at Senescence-Associated Heterochromatin Foci (SAHFs) that depend on the activity of H3K9 methyltransferases, on recruitment of HP1 proteins and histone chaperones, and on the presence of macro H2A. The decrease in activity of the maintenance DNA methyltransferase Dnmt1 and the increase in de novo Dnmt3 methyltransferases during aging may also contribute to heterochromatin redistribution.

None

Figure 2. Epigenetic changes resulting in a decrease and redistribution of global heterochromatin may underlie the various models of aging. The models of free radical accumulation, genetically programmed senescence, telomere shortening, genomic instability, nutritional intake and growth signaling are distinct, yet overlapping theories of aging that may all be linked by heterochromatin redistribution.

Similar articles

Cited by

References

    1. Hansen JC. Conformational dynamics of the chromatin fiber in solution: determinants, mechanisms, and functions. Annu Rev Biophys Biomol Struct. 2002;31:361–92. doi: 10.1146/annurev.biophys.31.101101.140858. - DOI - PubMed
    1. Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature. 1997;389:251–60. doi: 10.1038/38444. - DOI - PubMed
    1. Radak Z, Chung HY, Goto S. Exercise and hormesis: oxidative stress-related adaptation for successful aging. Biogerontology. 2005;6:71–5. doi: 10.1007/s10522-004-7386-7. - DOI - PubMed
    1. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128:693–705. doi: 10.1016/j.cell.2007.02.005. - DOI - PubMed
    1. Wallrath LL. Unfolding the mysteries of heterochromatin. Curr Opin Genet Dev. 1998;8:147–53. doi: 10.1016/S0959-437X(98)80135-4. - DOI - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources