Role of Serum and Glucocorticoid-Inducible Kinase (SGK)-1 in Senescence: A Novel Molecular Target Against Age-Related Diseases

Author(s): D. Lauro , D. Pastore , B. Capuani , F. Pacifici , R. Palmirotta , P. Abete , M. Roselli , A. Bellia , M. Federici , N. Di Daniele , P. Sbraccia , F. Guadagni , R. Lauro , D. Della-Morte .

Journal Name: Current Medicinal Chemistry

Volume 22 , Issue 33 , 2015

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Abstract:

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.

Keywords: Aging, apoptosis, cancer, inflammation, metabolic diseases, oxidative stress, SGK-1.

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Article Details

VOLUME: 22
ISSUE: 33
Year: 2015
Page: [3765 - 3788]
Pages: 24
DOI: 10.2174/0929867322666150812145035
Price: $58

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