Controversial Impact of Sirtuins in Chronic Non-Transmissible Diseases and Rehabilitation Medicine

Abstract

A large body of evidence reports about the positive effects of physical activity in pathophysiological conditions associated with aging. Physical exercise, alone or in combination with other medical therapies, unquestionably causes reduction of symptoms in chronic non-transmissible diseases often leading to significant amelioration or complete healing. The molecular basis of this exciting outcome—however, remain largely obscure. Epigenetics, exploring at the interface between environmental signals and the remodeling of chromatin structure, promises to shed light on this intriguing matter possibly contributing to the identification of novel therapeutic targets. In this review, we shall focalize on the role of sirtuins (Sirts) a class III histone deacetylases (HDACs), which function has been frequently associated, often with a controversial role, to the pathogenesis of aging-associated pathophysiological conditions, including cancer, cardiovascular, muscular, neurodegenerative, bones and respiratory diseases. Numerous studies, in fact, demonstrate that Sirt-dependent pathways are activated upon physical and cognitive exercises linking mitochondrial function, DNA structure remodeling and gene expression regulation to designed medical therapies leading to tangible beneficial outcomes. However, in similar conditions, other studies assign to sirtuins a negative pathophysiological role. In spite of this controversial effect, it is doubtless that studying sirtuins in chronic diseases might lead to an unprecedented improvement of life quality in the elderly.

Yiqigubiao pill treatment regulates Sirtuin 5 expression and mitochondrial function in chronic obstructive pulmonary disease

“…Sirtuins (Sirts) are found in all organisms and are involved in many other processes that occur within cells, including participation in the regulation of the cell cycle and energy metabolism, apoptosis, and oxidative stress processes ( 28 ). In fact, the functions of Sirts have been implicated in the pathogenesis of respiratory diseases, including COPD ( 29 ). Wang et al confirmed the involvement of SIRT5 in the process of COPD by inhibiting CSE-induced apoptosis of lung epithelial cells ( 30 ).…”

The epigenetic landscape of exercise in cardiac health and disease

“… 94 SIRTs have been frequently associated with an equivocal role in the pathologic process of aging-associated pathophysiological conditions, including cancer and cardiovascular, muscular, neurodegenerative, bone, and respiratory diseases. 95 , 96 , 97 , 98 Specifically, numerous studies have demonstrated that SIRT-dependent pathways are activated by exercise, which modulates chromatin structure, gene expression and mitochondrial function that lead to beneficial outcomes. 99 In addition to DNA methylation, histone trimethylation in histone-3 lysine-4 after exercise modulates PGC-1α, which upregulates PGC-1α and remodels metabolism of skeletal muscle.…”