Age‐associated increase in heterochromatic marks in murine and primate tissues

Aging Cell

Jill A. Kreiling¹  Mimi Tamamori-Adachi¹  Alec N. Sexton¹  Jessie C. Jeyapalan¹  Ursula Munoz-Najar¹  Abigail L. Peterson¹  Jayameenakshi Manivannan¹  Elizabeth S. Rogers¹  Nikolay A. Pchelintsev²  Peter D. Adams² 

[1] Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02903, USA;CRUK Beatson Labs, University of Glasgow, Glasgow G61 1BD, UK

关键词: aging;    cellular senescence;    epigenetics;    heterochromatin;    immunofluorescence;   

DOI  :  10.1111/j.1474-9726.2010.00666.x

来源: Wiley

【 摘 要 】

Summary

Chromatin is highly dynamic and subject to extensive remodeling under many physiologic conditions. Changes in chromatin that occur during the aging process are poorly documented and understood in higher organisms, such as mammals. We developed an immunofluorescence assay to quantitatively detect, at the single cell level, changes in the nuclear content of chromatin-associated proteins. We found increased levels of the heterochromatin-associated proteins histone macro H2A (mH2A) and heterochromatin protein 1 beta (HP1β) in human fibroblasts during replicative senescence in culture, and for the first time, an age-associated increase in these heterochromatin marks in several tissues of mice and primates. Mouse lung was characterized by monophasic mH2A expression histograms at both ages, and an increase in mean staining intensity at old age. In the mouse liver, we observed increased age-associated localization of mH2A to regions of pericentromeric heterochromatin. In the skeletal muscle, we found two populations of cells with either low or high mH2A levels. This pattern of expression was similar in mouse and baboon, and showed a clear increase in the proportion of nuclei with high mH2A levels in older animals. The frequencies of cells displaying evidence of increased heterochromatinization are too high to be readily accounted for by replicative or oncogene-induced cellular senescence, and are prominently found in terminally differentiated, postmitotic tissues that are not conventionally thought to be susceptible to senescence. Our findings distinguish specific chromatin states in individual cells of mammalian tissues, and provide a foundation to investigate further the progressive epigenetic changes that occur during aging.

【 授权许可】

Unknown   
© 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland