Resveratrol Ameliorates Mitochondrial Elongation via Drp1/Parkin/PINK1 Signaling in Senescent‐Like Cardiomyocytes

Abstract

Resveratrol is widely known for its antiaging properties and exerts cardiovascular protective effects in different experimental models. The role of resveratrol in regulating mitochondrial functions and dynamics during the cardiac aging process remains poorly understood. In this study, the effects of resveratrol on mitochondrial morphology and mitochondrial depolarization and on expressions of Drp1, parkin, PINK1, and LC3 were investigated in H9c2 cells after D-galactose treatment that induced senescent-like cardiomyocytes. The results show that downregulation of Drp1 markedly increased mitochondrial elongation. Senescent-like cardiomyocytes were more resistant to CCCP-induced mitochondrial depolarization, which was accompanied by suppressed expression of parkin, PINK1, and LC3-II. Resveratrol treatment significantly increased Drp1 expression, ameliorated mitochondrial elongation, and increased the mitochondrial translocations of parkin and PINK1. In addition, resveratrol significantly enhanced LC3-II expression and decreased TOM20-labeled mitochondrial content. Resveratrol also suppressed the phosphorylation of parkin and PINK1, which may relate to its abilities to degrade the impaired mitochondria in senescent-like cardiomyocytes. These findings show that suppressing mitochondrial elongation in a Drp1-dependent manner is involved in the effect of resveratrol on attenuating the development of aging cardiomyocytes. Activation of parkin and PINK1 may be a potential mechanism of resveratrol for treating cardiovascular complications related to aging.

Pharmacological basis and new insights of resveratrol action in the cardiovascular system

“…An increased mitochondrial biogenesis can ameliorate the impaired energy homeostasis of aging heart and vasculature. In senescent cardiomyocytes, resveratrol suppressed mitochondrial elongation through up‐regulating the expression of dynamin‐related protein 1 (Ren et al, ). The elongated and dysfunctional mitochondria eventually accumulate in cardiomyocytes, underlying the reduction in ischaemic preconditioning of aged hearts.…”

The Aging Heart: Mitophagy at the Center of Rejuvenation

“…Although autophagy is clearly diminished with age in tissues, including the heart (5,(9)(10)(11)(12), exactly why cardiac autophagy is reduced during aging is still unclear. Most of our current knowledge comes from studies in cell lines or other tissues.…”

“…It is also a key pathway in cellular quality control by eliminating dysfunctional or unwanted organelles and protein aggregates. However, there is strong evidence that autophagy is decreased with age in tissues, including the heart (5,(9)(10)(11)(12)(13)(14)(15).…”

Autophagy—A key pathway for cardiac health and longevity

“…There is strong evidence that both autophagy and mitophagy decrease with age in numerous tissues, including the heart . However, the mechanistic underpinnings for the age‐related decline in autophagy remain unclear and likely complex.…”

“…There is strong evidence that both autophagy and mitophagy decrease with age in numerous tissues, including the heart. [33][34][35][36] However, the mechanistic underpinnings for the age-related decline in autophagy remain unclear and likely complex. One simple yet plausible explanation is that the autophagy machinery is simply overburdened in the ageing cell, struggling to keep pace with increased ROS generation and oxidative damage.…”