SIRT1-induced deacetylation of Akt expedites platelet phagocytosis and delays HEMEC aging

Abstract

Maintaining the health of the endothelium is of critical importance to prevention against cell aging. The current study was performed to clarify the role of sirtuin1 (SIRT1) in platelet phagocytosis in cell aging and identified its downstream molecular mechanism. Platelet phagocytosis by human endometrial microvascular endothelial cells (HEMECs) was characterized by transmission electron and fluorescence microscopy. Functional experiments were conducted to examine platelet phagocytosis and cell aging using the overexpression or knockdown plasmids of SIRT1 and G alpha-interacting, vesicle-associated protein (GIRDIN) as well as Akt inhibitor and activator. It was found that SIRT1 facilitated platelet phagocytosis by HEMECs, contributing to inhibition of cell aging. Akt activation facilitated platelet phagocytosis and repressed cell aging. GIRDIN overexpression accelerated platelet phagocytosis by HEMECs, leading to a delay in cell aging. GIRDIN phosphorylation at Ser1417 was induced by Akt activation, while activation of Akt was induced by SIRT1-mediated deacetylation, consequently augmenting platelet phagocytosis and delaying cell aging. Taken together, SIRT1 delayed aging of HEMECs by deacetylating Akt, phosphorylating GIRDIN, and inducing platelet phagocytosis. The study highlights a possible target for the prevention of HEMEC aging.

An orchestra of machine learning methods reveals landmarks in single-cell data exemplified with aging fibroblasts

“…The second-ranked gene, Coiled-Coil Domain Containing 88A (CCDC88A), has also been associated with cancer and aging [ 44 , 45 ] and is involved in various biological processes, including tumor angiogenesis, cancer migration and invasion, tumor metastasis, and epithelial wound healing [ 44 ].…”

“…Besides being of interest due to its involvement in cancer and epithelial regeneration/repair [46], the role of CCDC88A in cell aging has also garnered interest due to its function as a direct downstream mediator of Akt signaling [45]. Lan et al (2021) observed in human endometrial microvascular endothelial cells (HEMECs) that the activation of CCDC88A, which is mediated by Sirtuin 1 (SIRT1) and its deacetylation of Akt and PDK1, which subsequently activate CCDC88A, results in delayed aging [45]. Both SIRT1 and Akt are involved in aging and have already been shown to play essential roles in HEMEC aging [45].…”

“…Lan et al (2021) observed in human endometrial microvascular endothelial cells (HEMECs) that the activation of CCDC88A, which is mediated by Sirtuin 1 (SIRT1) and its deacetylation of Akt and PDK1, which subsequently activate CCDC88A, results in delayed aging [45]. Both SIRT1 and Akt are involved in aging and have already been shown to play essential roles in HEMEC aging [45]. SIRT1, along with all Sirtuin isoforms, for example, is well-known as an attractive therapeutic target for aging-related diseases and for its activation by the Sirtuin activating compound resveratrol, which can be found in grapes and red wine [50].…”

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

“…In the last decade, researchers have found that the level of yeast Sir2 (a homolog of Sirt1) decreases as the increasing number of replications, which is one of the causes of yeast aging (Dang et al, 2009 ). Until now, accumulating scientific evidence indicates that the expression and activity of SIRT1 in mammalian cells decreased progressively with aging (Lamichane et al, 2019 ; Lin et al, 2020 ; Lan et al, 2021 ). This may be due to NAD+, the major cofactor of SIRT1, also shows a progressive decline with aging (Covarrubias et al, 2021b ).…”

Eicosapentaenoic Acid‐Enriched Phospholipids Alleviate Skeletal Muscle Atrophy in Lewis Lung Carcinoma Mouse Model

“…[14] SIRT1 directly deacetylates NF-𝜅B, Akt, FoxO3a, and PGC-1𝛼 to regulate their nuclear translocation and/or activities. [15][16][17][18] A growing body of evidence suggests that activation of SIRT1 could ameliorate several skeletal muscle diseases such as cancer, aging, glucocorticoids, and chronic kidney disease-induced muscle atrophy. [19][20][21][22] Thus, SIRT1 seems to be an attractive therapeutic target for preventing skeletal muscle atrophy.…”