Sirtuin 1 (SIRT1) is a NAD+_dependent class III histone deacetylase, and a key gene linked to control of longevity, gene silencing, cell cycle progression, apoptosis, inflammation, stress resistance and energy homeostasis. SIRT1 is activated in response to low cellular energy stores and have been implicated in the control of many physiological processes including senescence. SIRT1 also regulates steroid hormone signaling through a variety of molecular mechanisms and modulate pathways that modify steroid hormone receptors. Declining of sex steroid hormones, including estrogens and androgens, is involved in the aging process and age-related diseases such as sarcopenia, falling, osteoporosis, cognitive and mood disorders, cardiovascular diseases, and sexual disturbance.

In this review, we will focus on the effects of sex steroid hormones on SIRT1 gene expression in endothelial cells and the advantages in the treatments with each hormone will be discussed in terms of understanding mammalian aging and longevity control. The sirtuins comprise a family of enzymes belonging to class III histone deacetylase (HDAC), which operate by removing acetyl groups from histones and other protein regulatory factors, resulting infunctional consequences on chromatin remodeling and gene expression profiles. Moreover, the sirtuin family is highly conserved from archaebacteria to eukaryotes.

Energy metabolism is deeply involved in cellular aging. It is widely known that calorie restriction has the effect of suppressing aging and extending life span across species. In particular, moderate calorie restriction in humans ameliorates multiple metabolic and hormonal factors that are implicated in the pathogenesis of type 2 diabetes, cardiovascular diseases and cancer, that are the leading causes of morbidity, disability and mortality. SIRT1 also regulates steroid hormone signaling through a variety of molecular mechanisms and modulate pathways that modify steroid hormone receptors. Declining of sex steroid hormones, including estrogens and androgens, is involved in the aging process and age-related diseases such as sarcopenia, falling, osteoporosis, cognitive and mood disorders, cardiovascular diseases, and sexual disturbance.

Estrogen reduces the risk of developing atherosclerosis in premenopausal women, whereas in post-menopausal women who may have established atherosclerotic diseases, estrogen increases the risk of myocardial diseases through the effects on plaque stability and clot formation. Estrogens may also modulate cardiovascular health through expression of SIRT1, possibly in the AKT and ERK signal pathways.

Atherogenic stimuli, including diabetes, dyslipidemia, and oxidative stress, induce vascular dysfunction, leading to atherosclerosis, which is a key pathological basis for cardiovascular diseases such as ischemic heart diseases and strokes.

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