# Sirtuin 1 and Hormonal Regulations in Aging
## 3 SIRT1, Hypothalamus, and Endocrine Regulations
### SIRT1 and Other Hormonal Regulations  
The prevalence of type II diabetes increases markedly after the age of 65 years, largely due to the reduced sensitivity of pancreatic beta cells to incretins and insufficient insulin secretion, coupled with insulin resistance caused by obesity and reduced physical activity [36]. Furthermore, older men are more affected by these conditions due to declining testosterone levels and altered metabolic profiles. Increased expression of SIRT1 has been shown to reduce oxidative stress and prevent apoptosis in pancreatic beta cells, thereby increasing their insulin secretion [37]. In one study, SIRT1 activation by resveratrol (2.5 mg/kg/day) in a diabetic mouse model improved glucose tolerance and reduced hyperglycemia, demonstrating enhanced beta-cell function and insulin sensitivity [38]. Furthermore, during prolonged fasting, SIRT1 promotes energy production by facilitating fat oxidation, whereas during shorter periods of fasting it minimizes gluconeogenesis, conserving energy stores in mice [37]. SIRT1 also regulates glucose uptake in response to obestatin--a 23-amino acid peptide hormone derived from the preproghrelin transcript secreted primarily by the gastric mucosa--in the mouse 3T3-L1 preadipocyte cell line [39]. SIRT1 plays a critical role in the protection against diabetes-induced vascular cell self-lesions and matrix calcification by enhancing DNA repair mechanisms in diabetic vascular smooth muscle cells in mammals [2; 5; 40]. It has been shown that miRNA-34a, which induces senescence and promotes vascular calcification, suppresses SIRT1 expression and its anti-aging effects in murine blood vessels [41; 42]. Experimental data have shown that silencing miRNA-34a in old male mice (21 months) restores SIRT1 levels and reduces vascular calcification, underscoring the therapeutic potential of targeting miRNA-SIRT1 pathways [43]. The antidiabetic drug omarigliptin, an inhibitor of dipeptidyl peptidase-4 (DPP-4), stimulates SIRT1 expression and enhances its antioxidant activity, offering potential benefits for preventing atherosclerotic changes in high-fat diet-induced mice model of nonalcoholic fatty liver disease [44]. Overall, SIRT1 is considered to be a promising antidiabetic agent due to its beneficial effects on glucose homeostasis. In human low vitamin D3 levels have been associated with cardiovascular and cognitive pathologies [45], as well as with colorectal, breast and prostate cancer and colorectal adenoma [46]. In the elderly, reduced production of cholecalciferol in the epidermis impairs calcium absorption and increases the risk of osteoporosis [47]. Supplementation with the active form of vitamin D3 has been shown to promote myogenic differentiation in C2C12 myoblast cells and prevent myotube atrophy by regulating SIRT1 expression [48]. Furthermore, vitamin D3-induced SIRT1 expression significantly reduced senescent changes in human aortic endothelial cells exposed to the chemotherapeutic agent doxorubicin [49]. A study conducted on 4-week-old male Wistar rats demonstrated that vitamin D3 supplementation for 8 weeks significantly improved coronary arteriole function by enhancing SIRT1 expression and reducing oxidative stress markers, providing additional evidence for its protective role [50]. These findings suggest that vitamin D-activated SIRT1 expression may reduce the risk of various pathologies, including metabolic syndrome, cardiovascular disease, immune disorders, and chronic kidney disease [51]. SIRT1 also interacts with hormones such as irisin, a myokine produced by skeletal muscle fibers during intense exercise, and melatonin secreted by the pineal gland. Both hormones are potent antioxidants and act as anti-aging agents that help prevent cardiac and neurodegenerative disorders [6; 52; 53]. Irisin has been shown to reduce microvascular damage in lipopolysaccharide-induced acute lung injury in lipopolysaccharide-induced acute lung injury in male Sprague-Dawley rats and A549 cells by upregulating SIRT1 [54].