Senescence is a phenomenon characterized by a progressive decline of body homeostasis.
Premature senescence acts when the cellular system is not able to adequately respond
to noxious stimuli by synthesis of stressor molecules. Among those, serum-and-glucocorticoidinducible
kinase-1 (SGK-1) dramatically increases under typical physiopathological conditions, such as glucocorticoid
or mineralcorticoids exposure, inflammation, hyperglycemia, and ischemia. SGK-1 has been implicated
in mechanism regulating oxidative stress, apoptosis, and DNA damage, which are all leading to a
state of accelerating aging. Moreover, SGK-1-sensitive ion channels participate in the regulation of renal
Na+/K+ regulation, blood pressure, gastric acid secretion, cardiac action potential, and neuroexcitability. Recently,
we demonstrated in endothelial cells as an increase in SGK-1 activity and expression reduces oxidative
stress, improves cell survival and restores insulin-mediated nitric oxide production after hyperglycemia.
Moreover, we showed as SGK-1 delays the onset of senescence by increasing telomerase activity, significantly
decreasing reactive oxygen species (ROS) production, and by directly interacting with hTERT. Therefore,
SGK-1 may represent a specific target to further develop novel therapeutic options against chronic diseases
such as diabetes typical of aging. SGK-1 has been also associated with cancer, neurodegenerative diseases,
and cardiovascular disease, among other age-related diseases. However, to date, the data available on
SGK-1 and aging, are sparse, controversial, and only from C. elegans experimental models. In this review we
sought to discuss the possible implication of SGK-1 in mechanisms regulating senescence and age-related
diseases. Moreover, we aimed to discuss and identify the possible role of SGK-1 as possible molecular target
to counteract and prevent aging.