ATP-dependent chromatin remodelers in ageing and age-related disorders
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REVIEW ARTICLE
ATP-dependent chromatin remodelers in ageing and agerelated disorders Pynskhem Bok Swer . Ramesh Sharma
Received: 22 July 2020 / Accepted: 16 September 2020 Ó Springer Nature B.V. 2020
Abstract Ageing is characterized by the perturbation in cellular homeostasis associated with genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intracellular communication. Changes in the epigenome represent one of the crucial mechanisms during ageing and in age-related disorders. The ATP-dependent chromatin remodelers are an evolutionarily conserved family of nucleosome remodelling factors and generally regulate DNA repair, replication, recombination, transcription and cell cycle. Here, we review the chromatin based epigenetic changes that occur in ageing and agerelated disorders with a specific reference to chromatin remodelers. We also discuss the link between dietary restriction and chromatin remodelers in regulating age-related processes with a view for consideration in future intervention studies. Keywords Ageing Epigenetics Chromatin remodelers Dietary restriction
P. B. Swer R. Sharma (&) Department of Biochemistry, North-Eastern Hill University, Shillong 793022, India e-mail: [email protected]
Introduction Ageing, the process which manifests itself as the progressive decline in basic metabolic functions in a time-dependent manner, is contributed by myriad factors: the aetiology of which is broad and widespread. It is a common biological phenomenon in all living organisms and involves highly conserved longevity pathways (Pitt and Kaeberlein 2015). Although the pathways leading to ageing are conserved but the underlying mechanisms are different between the organisms being compared. In general, ageing increases the susceptibility to many chronic diseases which includes Alzheimer disease, chronic kidney disease, coronary artery disease, osteoarthritis, stroke, type 2 diabetes mellitus and common cancers, such as breast, prostate and colorectal cancer (Franceschi et al. 2018). Thus, slowing the ageing process might prevent some of these diseases or at least partially reverse features of ageing. Dietary restriction (DR), the reduction in calorie intake without malnutrition, has been shown to delay the ageing process and extend lifespan in multiple organisms (Sharma 2004; Kapahi et al. 2017). In addition, perturbation of the nutrient sensing and response pathways can have similar effects on longevity. Of note, the insulin-like signaling (ILS)/mechanistic target of rapamycin (mTOR) network has been found to play a central role in regulating life span in yeast, worms, fruit flies, and mice (Kenyon 2010; Johnson et al. 2013). The
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Biogerontology
beneficial effects of DR on health and longevity are mediated by the inhibition of ILS and mTOR. Attempts have been made over the years to categorize and understand v
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