Calcification of tissues involves the inappropriate deposition of calcium structures. It is a feature of aging in the cardiovascular system particularly, where calcification contributes to stiffening and dysfunction of tissues. Calcification proceeds alongside the development of atherosclerotic plaque, and thus has long been used as a marker to assess the extent of atherosclerotic cardiovascular disease, but it is a distinct mechanism and pathology. Two people with the same degree of vascular thickening and plaque development can have quite different degrees of calcification.
At the present time there is little that can be done about calcification of blood vessel walls and structures of the heart. As for many aspects of aging, there is evidence for some approaches to be able to modestly slow the progression of calcification, but means of robust and sizable reversal of calcification have yet to be developed. The best widely available approach achieved to date is EDTA chelation therapy, and this is nowhere near as effective or reliable as one might hope it to be.
In today's open access paper, researchers discuss the role of sirtuins in the mechanisms thought to be involved in modest slowing of vascular calcification. The primary point of focus is the long-standing antidiabetic drug metformin, and thus much of the data is derived from diabetic patients and mice. The likely effect sizes are small, and may be more relevant to a diabetic aging metabolism than to a normal aging metabolism. All in all, this is of more academic interest to those following the ongoing story of research into sirtuins than it is of relevance to efforts to treat aging as a medical condition.
Mechanism and treatment of Sirtuin family in vascular calcification
The SIRT family has shown potential in alleviating vascular aging by inhibiting inflammation, reducing endoplasmic reticulum stress, lowering mitochondrial oxidative stress, and promoting DNA damage repair, all of which contribute to the suppression of vascular calcification. Notably, SIRT1, SIRT2, SIRT3, SIRT6, and SIRT7 have demonstrated therapeutic potential in the treatment of vascular calcification (VC). The occurrence of VC involves the participation of multiple factors, primarily attributed to the abnormal deposition of calcium and phosphorus in the vascular wall. This article primarily discusses how the SIRT family can ameliorate VC through various.
Recently, some studies have confirmed that ferroptosis can promote VC, indicating that metformin may alleviate the development of hyperlipidemia-associated VC by inhibiting ferroptosis. Ferroptosis is a form of cell death characterized by iron-dependent lipid peroxidation, regulated by multiple pathways, including redox balance, lipid metabolism, and energy metabolism. Metformin enhances autophagy and inhibits abnormal cell proliferation through the AMPK/SIRT1-FoxO1 pathway, thereby mitigating oxidative stress in diabetic nephropathy. Previous studies have demonstrated that metformin can increase the expression of SIRT3 and GPX4, significantly elevate the levels of phosphorylated mTOR and phosphorylated AMPK, and improve polycystic ovary syndrome in mice by inhibiting ovarian ferroptosis.
SIRT proteins may serve as crucial intermediates for metformin's inhibition of ferroptosis-related vascular calcification. They play a synergistic role by regulating the antioxidant system, iron metabolism, and cellular phenotype transformation. Future research should concentrate on specific activation strategies for SIRT proteins, such as selective agonists, to enhance the targeted therapeutic effects of metformin.
Hesperidin has been shown to prevent the development of calcific aortic valve disease via the SIRT7-Nrf2-ARE axis. Future studies could further investigate the SIRT family's pathways that inhibit VC through ferroptosis. Moreover, the SIRT family influences VC through various signaling pathways, including the Wnt/β-catenin, Runx2, NF-κB, and JAK/STAT pathways, as well as the AMPK signaling pathway. Additionally, the role of the SIRT family in VC is noteworthy, with current research primarily focusing on SIRT1, SIRT2, SIRT3, SIRT6, and SIRT7, while the functions of other SIRT proteins in VC remain to be explored. Clinically, it has been observed that a significant number of patients requiring coronary intervention exhibit multiple calcifications in the vessel walls; thus, investigating methods to prevent and delay the progression of VC is a promising area for future research.
View the full article at FightAging
