SIRT1/SIRT3 Modulates Redox Homeostasis during Ischemia/Reperfusion in the Aging Heart

Abstract

Ischemia/reperfusion (I/R) injury is the central cause of global death in cardiovascular diseases, which is characterized by disorders such as angina, stroke, and peripheral vascular disease, finally causing severe debilitating diseases and death. The increased rates of morbidity and mortality caused by I/R are parallel with aging. Aging-associated cardiac physiological structural and functional deterioration were found to contribute to abnormal reactive oxygen species (ROS) production during I/R stress. Disturbed redox homeostasis could further trigger the related signaling pathways that lead to cardiac irreversible damages with mitochondria dysfunction and cell death. It is notable that sirtuin proteins are impaired in aged hearts and are critical to maintaining redox homeostasis via regulating substrate metabolism and inflammation and thus preserving cardiac function under stress. This review discussed the cellular and functional alterations upon I/R especially in aging hearts. We propose that mitochondria are the primary source of reactive oxygen species (ROS) that contribute to I/R injury in aged hearts. Then, we highlight the cardiomyocyte protection of the age-related proteins Sirtuin1 (SIRT1) and Sirtuin1 (SIRT3) in response to I/R injury, and we discuss their modulation of cardiac metabolism and the inflammatory reaction that is involved in ROS formation.

Sirtuin 3 deficiency aggravates angiotensin II‐induced hypertensive cardiac injury by the impairment of lymphangiogenesis

“…Previous studies have found that Ang II cause hypertension and hypertensive cardiac hypertrophy and fibrosis 23,24 . SIRT3 can protect the heart from multiple types of diseases which cause cardiac hypertrophy and fibrosis, through the regulation of oxidative stress, metabolism and aging 14,25‐27 . It was consistent with the previous study that SIRT3 deficiency aggravated Ang II‐induced heart injury.…”

Moringa oleifera Leaf Extract Upregulates Nrf2/HO-1 Expression and Ameliorates Redox Status in C2C12 Skeletal Muscle Cells

“…Our previous study showed that Moringa oleifera leaf extract (MOLE), due to the presence of glucosinolates, flavonoids and phenolic acids, improved oxidative capacity in C2C12 skeletal muscle cells, as displayed by the increased reliance on fat metabolism through the activation of the SIRT1-PPARα pathway [ 21 ]. Indeed, a number of studies has shown that SIRT1, besides being a critical energy sensor able to modulate transcription factors involved in muscle mitochondrial biogenesis and function [ 22 , 23 ], is also involved in maintaining cellular redox homeostasis [ 24 , 25 ]. In fact, this protein is very effective in attenuating oxidative stress through the deacetylation of transcription factors, including nuclear factor erythroid 2-related factor (Nrf2) [ 26 ], and in such a way potentiates the cellular defense system.…”

Role of Oxidative DNA Damage and Repair in Atrial Fibrillation and Ischemic Heart Disease

“…NAD + is also a rate-limiting co-substrate for sirtuin family proteins (SIRT1-7), which all serve as important regulators of redox homeostasis and are implicated in various cardiac diseases [ 189 , 190 ]. NAD + depletion will thus lead to reduction in the activity of SIRT1 [ 191 ] and SIRT3 [ 192 ], which impairs mitochondrial biogenesis and antioxidant defense, further enhancing mitochondrial dysfunction, one of the hallmarks of IRI [ 193 ] ( Figure 4 ).…”