title: Longevity Pathways (mTOR, SIRT, Insulin/IGF-1) as Key Modulatory Targets on Aging and Neurodegeneration.
abstract: Recent data from epidemiologic studies have shown that the majority of the public health costs are related to age-related disorders, and most of these diseases can lead to neuronal death. The specific signaling mechanisms underpinning neurodegeneration and aging are incompletely understood. Much work has been directed to the search for the etiology of neurodegeneration and aging and to new therapeutic strategies, including not only drugs but also non-pharmacological approaches, such as physical exercise and low-calorie dietary intake. The most important processes in aging-associated conditions, including neurodegeneration, include the mammalian (or mechanistic target of rapamycin (mTOR, sirtuin (SIRT and insulin/insulin growth factor 1 signaling (IIS pathways. These longevity pathways are involved in an array of different processes, including metabolism, cognition, stress response and brain plasticity. In this review we focus on the current advances involving the mTOR, SIRT and IIS longevity pathways during the course of healthy aging processes and neurodegenerative diseases, bringing new insights in the form of a better understanding of the signaling mechanisms underpinning neurodegeneration and how these differ from physiological normal aging processes. This also provides new targets for the therapeutic management and/or prevention of these devastating age-related disorders.
authors.forename: Caio Henrique
authors.initials: CH
authors.lastname: Mazucanti
authors.forename: João Victor
authors.initials: JV
authors.lastname: Cabral-Costa
authors.forename: Andrea Rodrigues
authors.initials: AR
authors.lastname: Vasconcelos
authors.forename: Diana Zukas
authors.initials: DZ
authors.lastname: Andreotti
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Scavone
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, Avenida Professor Lineu Prestes, 1524, São Paulo, Brazil, 05508-900. kawamotoe@gmail.com.
authors.forename: Elisa Mitiko
authors.initials: EM
authors.lastname: Kawamoto
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D058990:Molecular Targeted Therapy / Q000379:methods*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1