SIRT3/6: an amazing challenge and opportunity in the fight against fibrosis and aging

Abstract

Fibrosis is a typical aging-related pathological process involving almost all organs, including the heart, kidney, liver, lung, and skin. Fibrogenesis is a highly orchestrated process defined by sequences of cellular response and molecular signals mechanisms underlying the disease. In pathophysiologic conditions associated with organ fibrosis, a variety of injurious stimuli such as metabolic disorders, epigenetic changes, and aging may induce the progression of fibrosis. Sirtuins protein is a kind of deacetylase which can regulate cell metabolism and participate in a variety of cell physiological functions. In this review, we outline our current understanding of common principles of fibrogenic mechanisms and the functional role of SIRT3/6 in aging-related fibrosis. In addition, sequences of novel protective strategies have been identified directly or indirectly according to these mechanisms. Here, we highlight the role and biological function of SIRT3/6 focus on aging fibrosis, as well as their inhibitors and activators as novel preventative or therapeutic interventions for aging-related tissue fibrosis.

Keywords: Aging; Fibrosis; SIRT3; SIRT6; Signal pathway.

Fig. 1

The role of SIRT3 and SIRT6 in several tissue fibrosis diseases. Mechanically, tissue fibrosis diseases include liver fibrosis, kidney fibrosis, lung fibrosis, and cardiac fibrosis

Fig. 2

Schematic representation of the pathological mechanism of SIRT3/6 in fibrosis and aging. The pathological process of fibrosis is characterized by inflammation, oxidative stress, and apoptosis and energy metabolism. ETC electron transport chain; MnSOD manganese superoxide dismutase; PI3K phosphatidylinositol 3-kinase