Research Paper Advance Articles

The effects of early-life growth hormone intervention on tissue specific histone H3 modifications in long-lived Ames dwarf mice

Fang Zhang1, , Mert Icyuz1, , Andrzej Bartke2, , Liou Y. Sun1, ,

  • 1 Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35254, USA
  • 2 Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62702, USA

Received: September 15, 2020       Accepted: October 29, 2020       Published: December 28, 2020      

https://doi.org/10.18632/aging.202451
How to Cite

Copyright: © 2020 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Histone modifications, specifically in the lysine residues of histone H3, have been implicated in lifespan regulation in several model organisms. Our previous studies showed that growth hormone (GH) treatment during early life can dramatically influence lifespan in long-lived Ames dwarf mice. However, the effects of this hormonal intervention on epigenetic modifications have never been examined. In this study, we sought to compare tissue-specific histone H3 lysine methylation and acetylation markers in Ames dwarf and wild type (WT) mice and to determine how these markers are affected by early-life GH intervention. Ames dwarf mice exhibited suppressed H3K4me in both hepatic and brain tissues, while showing elevated H3K27me in the brain. Early-life GH intervention significantly altered the histone H3 markers in those tissues. Furthermore, early GH intervention increased expression of histone H3 acetylation at multiple lysine residues in a tissue-specific manner. This included changes in H3K14ac and H3K18ac in the liver and brain, H3K18ac in visceral adipose tissue and H3K9ac, H3K14ac and H3K27ac in subcutaneous adipose tissue. This study serves as an initial, but important step in elucidating the epigenetic mechanisms by which hormonal signals during early life can influence aging and longevity in mammals.

Abbreviations

GH: growth hormone; WT: wild type; DNMTs: DNA methyltransferases; AD: Alzheimer's disease; H3K4me3: tri-methylation of histone H3 at lysine 4; H3K27me3: tri-methylation of histone H3 at lysine 27; H3K9ac: acetylation in the 9 lysine of histone H3; H3K14ac: acetylation in lysine 14 of histone H3; H3K18ac: acetylation in lysine 18 of histone H3; H3K27ac: Lysine 27 acetylation in histone H3; H3K56ac: Acetylation of lysine 56 in histone H3; EZH2: enhancer of zeste homolog 2.