Rapamycin for longevity- opinion article. Zoya N. Demidenko

GSK-3 as potential target for therapeutic intervention in cancer ABSTRACT The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. GSK-3 functions in a wide range of cellular processes. Aberrant activity of GSK-3 has been implicated in many human pathologies including: bipolar depression, Alzheimer’s disease, Parkinson’s disease, cancer, non-insulin-dependent diabetes mellitus (NIDDM) and others. In some cases, suppression of GSK-3 activity by phosphorylation by Akt and other kinases has been associated with cancer progression. In these cases, GSK-3 has tumor suppressor functions. In other cases, GSK-3 has been associated with tumor progression by stabilizing components of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties. While many inhibitors to GSK-3 have been developed, their use remains controversial because of the ambiguous role of GSK-3 in cancer development. In this r...

Recent progress in targeting cancer Abstract In recent years, numerous new targets have been identified and new experimental therapeutics have been developed. Importantly, existing non-cancer drugs found novel use in cancer therapy. And even more importantly, new original therapeutic strategies to increase potency, selectivity and decrease detrimental side effects have been evaluated. Here we review some recent advances in targeting cancer. In 1977, Andrzej “Andrew” V. Schally won Nobel Prize in medicine for his research into peptide hormone production in the brain. He described the neurohormone GnRH and other releasing hormones (RH). As initially unexpected application, agonists and antagonists of these hormones have become investigational anti-cancer agents [ 1 - 3 ]. As further developments, Schally and coworkers described targeting gastrin releasing peptide receptors. Gastrin-releasing peptide (GRP) is involved in cancer growth and GRP receptors are expressed in a variety of cancer...

Rapamycin for life: A step to immortality Tumor suppression is admittedly the moststudied feature of p53. Nevertheless, numerous studies have portrayed p53 as key regulator of several normal biological processes, such as tissue homeostasis, development, differentiation and fertility.1 A seminal work by Hu and colleagues revealed that p53 regulates maternal reproduction through leukemia inhibitory factor (LIF) induction in mice.2 A recent report by Sohr and Engeland extends this observation and suggests a role for p53 in the blastocyst implantation process in humans as well.3 The authors show that CGB7, one of the genes encoding the b subunit of human chorionic gonadotropin (hCG), is transcriptionally induced by p53. hCG is a primate-specific hormone that is crucial for blastocyst implantation and early propagation of pregnancy. Interestingly, the other hCG-b-encoding genes were not induced by p53, thus implying a specific regulation leading to different  functions of these c...

Chronological lifespan in stationary culture: from yeast to human cells A decade ago, Mikhail Blagosklonny predicted that cellular senescence is driven by mitogenic pathways, when the cell cycle is blocked and actual growth is impossible [1]. In particular, the mitogen- and nutrientsensing mTOR (Target of Rapamycin) pathway drives either cell mass growth or aging [2]. Rapamycin prevents conversion of reversible cell cycle arrest to senescence [3-11]. When the cell cycle is blocked, but mTOR is still active, then cells become senescent. This process was named gerogenic conversion or simply geroconversion [12]. Rapamycin did not by-pass arrest but suppress geroconversion. Cells remained resting but not senescent. The discovery of mTOR-dependent geroconversion allowed Blagosklonny to connect cellular aging to age-related diseases and organismal aging [13, 14]. Furthermore, this predicted that rapamycin is a gerosuppressant, which could be used to prevent age-related diseases by slowing do...