# Sirtuin 1 and Hormonal Regulations in Aging
###### Abstract  
Aging affects the structure and functions of all organs and systems in the organism. In the elderly, significant changes in hormonal levels are observed. These translate to a predisposition for chronic diseases, including cardiovascular, neurodegenerative, and metabolic disorders. Therefore, tremendous scientific effort is focused on investigating molecular mechanisms and drugs with the potential to reduce hormonal changes in old age and their impact. Sirtuin 1 (SIRT1), a member of the sirtuin family of deacetylases, has been extensively studied as a regulator of multiple pathways related to antioxidant properties, optimal immune response, and metabolism. SIRT1 plays a key role in regulating various hormonal pathways and maintaining homeostasis. In the present study, we review the interplay between SIRT1 and hormonal regulations, including the endocrine role of the hypothalamic-pituitary-thyroid, -adrenal, -gonadal, and -liver axes, of other endocrine glands, and of non-endocrine tissues in the aging organism. The application of natural SIRT1 activators, such as resveratrol, curcumin, paeonol, and Buyang Huanwu Decoction, for the treatment of aging and senescence is discussed. SIRT1 activators improve mitochondrial function, reduce oxidative stress, and promote longevity, but their clinical application is limited by low bioavailability and poor permeability across biological barriers. For this reason, advanced delivery strategies are being considered, including nose-to-brain drug delivery and nanotechnology-based formulations. s 2024202024  
the liver via growth hormone (Figures 1 and 2). In addition, the hypothalamus secretes the neurohormones vasopressin and oxytocin. Sympathetic autonomic neurons, which are also under hypothalamic control, activate the secretion of adrenaline, noradrenaline, and dopamine from the adrenal medulla [1]. The autonomic nervous system also regulates other endocrine cells. Aging is a process of gradual decline in physiological functions and an increase in the risk of various diseases, including cardiovascular, metabolic, and neurodegenerative disorders. Hormonal changes play a key role in the aging process, affecting homeostasis, metabolism, and overall health. Recent studies highlight the importance of sirtuins, particularly Sirutin 1 (SIRT1), for regulating various hormonal pathways that contribute to aging and age-related diseases. SIRT1, the most studied member of the sirtuin family of NAD\({}^{+}\)-dependent deacetylases with ADP-ribosyl transferase activity [2], is known for its ability to influence cellular homeostasis, stress response, and longevity by regulating the expression of key genes involved in metabolism, inflammation, oxidative stress, and hormonal release [3; 4; 5; 6]. In addition to its role in metabolism and hormonal regulation, SIRT1 interacts with several other aging-related processes. For example, SIRT1 plays a critical role in modulating the oxidative stress response by activating antioxidant defense mechanisms such as upregulation superoxide dismutase (SOD) and catalase. It also suppresses the production of reactive oxygen species (ROS) through the inhibition of pro-oxidative factors such as nuclear factor-\(\kappa\)B (NF-\(\kappa\)B) [4; 5; 6]. Furthermore, SIRT1 contributes to the immune response by influencing the activity of immune cells, including T cells and macrophages, which are pivotal for maintaining homeostasis and combating age-related inflammation. SIRT1-mediated deacetylation of transcription factors such as forkhead box O (FOXO) proteins and p53 further underscores its role in integrating stress signals and coordinating cellular defense mechanisms. Natural compounds such as resveratrol, curcumin, and paeonol have been identified as activators of SIRT1, demonstrating potential therapeutic benefits for combating age-related hormonal imbalance and for extending life [5; 6; 7; 8].