Protein kinase A signaling as an anti-aging target

Protein kinase A (PICA) is a multi-unit protein kinase that mediates signal transduction of G-protein-coupled receptors through its activation by adenyl cyclase (AC)-mediated cAMP. The vital importance of PICA signaling to cellular function is reflected in the widespread expression of PKA subunit genes. As one of its many functions, PICA plays a key role in the regulation of metabolism and triglyceride storage. The PKA pathway has become of great interest to the study of aging, since mutations that cause a reduction in PICA signaling have been shown to extend lifespan in yeast, and to both delay the incidence and severity of age-related disease, and to promote leanness and longevity, in mice. There in increasing interest in the potential for the inhibition or redistribution of adiposity to attenuate aging, since obesity is associated with impaired function of most organ systems, and is a strong risk factor for shortened life span. Its association with coronary heart disease, hypertension, type 2 diabetes, cancer, sleep apnea and osteoarthritis is leading to its accession as a major cause of global ill health. Therefore, gene signaling pathways such as PICA that promote adiposity are potential inhibitory targets for aging intervention. Since numerous plant compounds have been found that both prevent adipogenesis and inhibit PKA signaling, a focused investigation into their effects on biological systems and the corresponding molecular mechanisms would be of high relevance to the discovery of novel and non-toxic compounds that promote healthy aging. (C) 2010 Elsevier Ireland Ltd. All rights reserved.