Relieving Cellular Energy Stress in Aging, Neurodegenerative, and Metabolic Diseases, SIRT1 as a Therapeutic and Promising Node

Abstract

The intracellular energy state will alter under the influence of physiological or pathological stimuli. In response to this change, cells usually mobilize various molecules and their mechanisms to promote the stability of the intracellular energy status. Mitochondria are the main source of ATP. Previous studies have found that the function of mitochondria is impaired in aging, neurodegenerative diseases, and metabolic diseases, and the damaged mitochondria bring lower ATP production, which further worsens the progression of the disease. Silent information regulator-1 (SIRT1) is a multipotent molecule that participates in the regulation of important biological processes in cells, including cellular metabolism, cell senescence, and inflammation. In this review, we mainly discuss that promoting the expression and activity of SIRT1 contributes to alleviating the energy stress produced by physiological and pathological conditions. The review also discusses the mechanism of precise regulation of SIRT1 expression and activity in various dimensions. Finally, according to the characteristics of this mechanism in promoting the recovery of mitochondrial function, the relationship between current pharmacological preparations and aging, neurodegenerative diseases, metabolic diseases, and other diseases was analyzed.

Prefoldin Function in Cellular Protein Homeostasis and Human Diseases

“…The holdase function of prefoldin is ATP-independent, similar to stress-inducible small HSPs ( Webster et al, 2019 ). Its ATP independence raises the question of whether prefoldin has additional functions under conditions of low cellular energy levels such as mitochondrial dysfunction and metabolic disorders, aging, or chronic stress ( Chaudhari and Kipreos, 2018 ; Andreasson et al, 2019 ; Fang et al, 2021 ).…”

The ABA-LANCL1/2 Hormone-Receptors System Protects H9c2 Cardiomyocytes from Hypoxia-Induced Mitochondrial Injury via an AMPK- and NO-Mediated Mechanism

“…Given its pivotal role in the control of energy expenditure, it is not surprising that a dysfunctional AMPK/PGC-1α/Sirt1 signaling axis should be responsible for reduced muscle energy expenditure, as occurs in aging and in metabolic disorders, such as type 2 diabetes (T2D) [ 49 ]. Consequently, pharmacological activation of this pathway holds promise as a new strategy to protect muscle and heart function under conditions that reduce myocyte vitality (aging, hypoxia, diabetes) [ 28 , 50 , 51 , 52 , 53 ].…”

Sirt1 overexpression improves senescence‐associated pulmonary fibrosis induced by vitamin D deficiency through downregulating IL‐11 transcription

“…Sirt1 is a member of the class III histone deacetylases with important regulatory roles in a variety of pathophysiological processes (Zeng et al, 2017). Accumulating evidence has shown that Sirt1 plays a protective role in preventing cellular metabolism, cell senescence, and inflammation by regulating several signaling pathways, especially via its ability to deacetylate target proteins (Fang et al, 2021; Xu et al, 2020). Sirt1 not only catalyzes the deacetylation of lysine residues in histone substrates such as H1, H3, and H4, but also removes many acetyl groups from nonhistone substrates (Ren et al, 2019), including peroxisome proliferator‐activated receptor‐γ coactivator‐1α, forkhead box class O family, Nrf1/2, p53, eIF2α (Prola et al, 2017), NF‐κB, and others (Maiese, 2021).…”