Role of Serum and Glucocorticoid-Inducible Kinase (SGK)-1 in senescence: A novel molecular target against age-related diseases

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3765-3788
Number of pages24
JournalCurrent Medicinal Chemistry
Volume22
Issue number33
Publication statusPublished - Dec 1 2015

    Fingerprint

Keywords

  • Aging
  • Apoptosis
  • Cancer
  • Inflammation
  • Metabolic diseases
  • Oxidative stress
  • SGK-1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Lauro, D., Pastore, D., Capuani, B., Pacifici, F., Palmirotta, R., Abete, P., Roselli, M., Bellia, A., Federici, M., Di Daniele, N., Sbraccia, P., Guadagni, F., Lauro, R., & Della-Morte, D. (2015). Role of Serum and Glucocorticoid-Inducible Kinase (SGK)-1 in senescence: A novel molecular target against age-related diseases. Current Medicinal Chemistry, 22(33), 3765-3788.