Estradiol as the Trigger of Sirtuin-1-Dependent Cell Signaling with a Potential Utility in Anti-Aging Therapies

Abstract

Aging entails the inevitable loss of the structural and functional integrity of cells and tissues during the lifetime. It is a highly hormone-dependent process; although, the exact mechanism of hormone involvement, including sex hormones, is unclear. The marked suppression of estradiol synthesis during menopause suggests that the hormone may be crucial in maintaining cell lifespan and viability in women. Recent studies also indicate that the same may be true for men. Similar anti-aging features are attributed to sirtuin 1 (SIRT1), which may possibly be linked at the molecular level with estradiol. This finding may be valuable for understanding the aging process, its regulation, and possible prevention against unhealthy aging. The following article summarizes the initial studies published in this field with a focus on age-associated diseases, like cancer, cardiovascular disease and atherogenic metabolic shift, osteoarthritis, osteoporosis, and muscle damage, as well as neurodegenerative and neuropsychiatric diseases.

Keywords: aging; estradiol; sirtuin 1.

Figure 1

Estradiol (E2) or phytoestrogens (PEs) interact with one of the estrogen receptors (ERs) and intensify the activity of sirtuin 1 (SIRT1), which may increase the expression of the ER. SIRT1 modulates the activity of transcription factors involved in the processes regulating, among others, osteogenesis, chondrogenesis, the metabolism of molecules affecting the rate of atherogenesis, cardiac fibrosis and hypertrophy, neuroprotection, and carcinogenesis.