title: Sixty years old is the breakpoint of human frontal cortex aging.
abstract: Human brain aging is the physiological process which underlies as cause of cognitive decline in the elderly and the main risk factor for neurodegenerative diseases such as Alzheimer's disease. Human neurons are functional throughout a healthy adult lifespan, yet the mechanisms that maintain function and protect against neurodegenerative processes during aging are unknown. Here we show that protein oxidative and glycoxidative damage significantly increases during human brain aging, with a breakpoint at 60 years old. This trajectory is coincident with a decrease in the content of the mitochondrial respiratory chain complex I-IV. We suggest that the deterioration in oxidative stress homeostasis during aging induces an adaptive response of stress resistance mechanisms based on the sustained expression of REST, and increased or decreased expression of Akt and mTOR, respectively, over the adult lifespan in order to preserve cell neural survival and function.
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain. Electronic address: rosanna.cabre@mex.udl.cat.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Cabré
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain. Electronic address: alba.naudi@mex.udl.cat.
authors.forename: Alba
authors.initials: A
authors.lastname: Naudí
authors.affiliation: Institute of Neuropathology, Department of Pathology and Experimental Therapeutics, University of Barcelona, E-08908 L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: mdominguezg@idibell.cat.
authors.forename: Mayelin
authors.initials: M
authors.lastname: Dominguez-Gonzalez
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain. Electronic address: victoria.ayala@mex.udl.cat.
authors.forename: Victòria
authors.initials: V
authors.lastname: Ayala
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain. Electronic address: mariona.jove@udl.cat.
authors.forename: Mariona
authors.initials: M
authors.lastname: Jové
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain. Electronic address: natalia.mota@mex.udl.cat.
authors.forename: Natalia
authors.initials: N
authors.lastname: Mota-Martorell
authors.affiliation: Neurology Division, Hospital Santa Maria of Lleida, E-25006 Lleida, Spain. Electronic address: gpinol@gss.scs.es.
authors.forename: Gerard
authors.initials: G
authors.lastname: Piñol-Ripoll
authors.affiliation: Neurology Division, Hospital Santa Maria of Lleida, E-25006 Lleida, Spain. Electronic address: mapi.gil.villar@gmail.com.
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Gil-Villar
authors.affiliation: Department of Basic Medical Sciences, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain. Electronic address: montse.rue@cmb.udl.cat.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rué
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain. Electronic address: manuel.portero@mex.udl.cat.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portero-Otín
authors.affiliation: Institute of Neuropathology, Department of Pathology and Experimental Therapeutics, University of Barcelona, E-08908 L'Hospitalet de Llobregat, Barcelona, Spain; Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), ISCIII, Spain. Electronic address: 8082ifa@gmail.com.
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Department of Experimental Medicine, University of Lleida-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), E-25198 Lleida, Spain. Electronic address: reinald.pamplona@mex.udl.cat.
authors.forename: Reinald
authors.initials: R
authors.lastname: Pamplona
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D015415:Biomarkers / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D059467:Transcriptome; D000099229:RE1-Silencing Transcription Factor
chemical_list: D015415:Biomarkers; D045222:Electron Transport Chain Complex Proteins; D051057:Proto-Oncogene Proteins c-akt; D012097:Repressor Proteins; D058570:TOR Serine-Threonine Kinases; D000099229:RE1-Silencing Transcription Factor; C546842:MTOR protein, human
keywords: Cell survival pathways; Mechanistic target of rapamycin (mTOR); Mitochondria respiratory chain; Mitochondrial stress; Protein oxidation; Repressor element 1-silencing transcription factor (REST)