Abstract
The senescence-accelerated SAMP8 mouse model displays features of cognitive decline and Alzheimer's disease. With the purpose of identifying potential epigenetic markers involved in aging and neurodegeneration, here we analyzed the expression of 84 mature miRNAs, the expression of histone-acetylation regulatory genes and the global histone acetylation in the hippocampus of 8-month-old SAMP8 mice, using SAMR1 mice as control. We also examined the modulation of these parameters by 8 weeks of voluntary exercise. Twenty-one miRNAs were differentially expressed between sedentary SAMP8 and SAMR1 mice and seven miRNAs were responsive to exercise in both strains. SAMP8 mice showed alterations in genes involved in protein acetylation homeostasis such as Sirt1 and Hdac6 and modulation of Hdac3 and Hdac5 gene expression by exercise. Global histone H3 acetylation levels were reduced in SAMP8 compared with SAMR1 mice and reached control levels in response to exercise. In sum, data presented here provide new candidate epigenetic markers for aging and neurodegeneration and suggest that exercise training may prevent or delay some epigenetic alterations associated with accelerated aging.
Highlights
Epigenetic changes are currently recognized as part of the aging process and have been implicated in many age-related chronic diseases (Jakovcevski and Akbarian, 2012; Akbarian et al, 2013; Lopez-Otin et al, 2013)
Altered expression of miRNAs has been described in different chronic pathologies and they are currently considered to be critical in the aging process (Jung and Suh, 2012). miRNAs seem to play an important role in the developing nervous system, in the physiology of high-order brain functions such as learning, memory, and emotion regulation, and in the manifestation of neurological disorders such as amyotrophic lateral sclerosis, Tourette’s syndrome, Alzheimer’s disease (AD) and others (Yang et al, 2007; Mastroeni et al, 2011; Goldie and Cairns, 2012; Van Den Hove et al, 2014)
With the purpose of identifying potential epigenetic markers involved in aging and neurodegeneration, here we studied the expression levels of a set of 84 mature miRNAs with reported effects on neurological development and disease, the expression of several genes involved in maintenance of the histone acetylation balance (HATs and histone deacetylases (HDACs)) and the levels of histone global acetylation (H3ac, H4ac) in the hippocampus of 8-monthold SAMP8 and SAMR1 mice
Summary
Epigenetic changes are currently recognized as part of the aging process and have been implicated in many age-related chronic diseases (Jakovcevski and Akbarian, 2012; Akbarian et al, 2013; Lopez-Otin et al, 2013). The term epigenetics includes a variety of processes known to regulate gene expression in a stable and potentially reversible way, without altering the primary DNA sequence (Jaenisch and Bird, 2003). Altered expression of miRNAs has been described in different chronic pathologies and they are currently considered to be critical in the aging process (Jung and Suh, 2012). HATs transfer an acetyl group to the amino groups of histone lysine residues and generally increase DNA transcription. For their part, HDACs decrease DNA accessibility by deacetylation of histone lysines (Legube and Trouche, 2003). Alterations in histone acetylation levels have been observed in several models of neurodegenerative diseases, including AD (Scheff et al, 2007; Arendt, 2009)
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