Aging Triggers H3K27 Trimethylation Hoarding in the Chromatin of Nothobranchius furzeri Skeletal Muscle.

Chiara Cencioni,Johanna Heid,Stefan Guenther,Seyed Mohammad Mahdi Rasa,Carlo Gaetano,Alessandro Cellerino,Mario Baumgart,Carsten Kuenne,Anna Krepelova,Francesco Neri,Francesco Spallotta

doi:10.3390/cells8101169

Abstract

Aging associates with progressive loss of skeletal muscle function, sometimes leading to sarcopenia, a process characterized by impaired mobility and weakening of muscle strength. Since aging associates with profound epigenetic changes, epigenetic landscape alteration analysis in the skeletal muscle promises to highlight molecular mechanisms of age-associated alteration in skeletal muscle. This study was conducted exploiting the short-lived turquoise killifish Nothobranchius furzeri (Nfu), a relatively new model for aging studies. The epigenetic analysis suggested a less accessible and more condensed chromatin in old Nfu skeletal muscle. Specifically, an accumulation of heterochromatin regions was observed as a consequence of increased levels of H3K27me3, HP1α, polycomb complex subunits, and senescence-associated heterochromatic foci (SAHFs). Consistently, euchromatin histone marks, including H3K9ac, were significantly reduced. In this context, integrated bioinformatics analysis of RNASeq and ChIPSeq, related to skeletal muscle of Nfu at different ages, revealed a down-modulation of genes involved in cell cycle, differentiation, and DNA repair and an up-regulation of inflammation and senescence genes. Undoubtedly, more studies are needed to disclose the detailed mechanisms; however, our approach enlightened unprecedented features of Nfu skeletal muscle aging, potentially associated with swimming impairment and reduced mobility typical of old Nfu.

Highlights

In the last two centuries, life expectancy in Western countries has increased considerably, dramatically enlarging the elderly people population
Very little is known about the chromatin landscape of Nothobranchius furzeri (Nfu) skeletal muscle and how it changes during aging
In old skeletal muscle tissue, we observed a significant increase in H3K27me3, H3K9me3, and H4K20me3 (Figure 1a)

Summary

Introduction

In the last two centuries, life expectancy in Western countries has increased considerably, dramatically enlarging the elderly people population. The risk of developing aging-associated diseases, including cardiovascular disease, dementia, and cancer, will continue to rise [4]. This situation challenges health and social systems, with a significant economic impact worldwide. Aging is accompanied by an overall loss of fitness and a decline of cell and organ function, associated with a reduced regenerative capacity and life expectancy [5]. In this context, the understanding of aging-associated molecular mechanisms is an unmet need to test novel approaches able to promote healthy aging and improve quality of life in the growing elderly population

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