title: Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging.
abstract: Centenarians not only enjoy an extraordinary aging, but also show a compression of morbidity. Using functional transcriptomic analysis of peripheral blood mononuclear cells (PMBC) we identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. Sub-network analysis led us to identify Bcl-xL as an important gene up-regulated in centenarians. It is involved in the control of apoptosis, cellular damage protection and also in modulation of immune response, all associated to healthy aging. Indeed, centenarians display lower plasma cytochrome C levels, higher mitochondrial membrane potential and also less cellular damage accumulation than septuagenarians. Leukocyte chemotaxis and NK cell activity are significantly impaired in septuagenarians compared with young people whereas centenarians maintain them. To further ascertain the functional role of Bcl-xL in cellular aging, we found that lymphocytes from septuagenarians transduced with Bcl-xL display a reduction in senescent-related markers. Finally, to demonstrate the role of Bcl-xL in longevity at the organism level,C. elegansbearing a gain of function mutation in the Bcl-xL orthologced-9, showed a significant increase in mean and maximal life span. These results show that mRNA expression in centenarians is unique and reveals that Bcl-xL plays an important role in exceptional aging.
authors: Facultad de Medicina, Universidad de Valencia, Valencia, Spain, INCLIVA and Spanish Centenarian Study Group; Facultad de Fisioterapia Universidad de Valencia, Valencia, Spain.
authors: Consuelo
authors: C
authors: Borras
authors: Facultad de Medicina, Universidad de Valencia, Valencia, Spain, INCLIVA and Spanish Centenarian Study Group; Facultad de Fisioterapia Universidad de Valencia, Valencia, Spain.
authors: Kheira M
authors: KM
authors: Abdelaziz
authors: Facultad de Medicina, Universidad de Valencia, Valencia, Spain, INCLIVA and Spanish Centenarian Study Group; Facultad de Fisioterapia Universidad de Valencia, Valencia, Spain.
authors: Juan
authors: J
authors: Gambini
authors: Facultad de Medicina, Universidad de Valencia, Valencia, Spain, INCLIVA and Spanish Centenarian Study Group; Facultad de Fisioterapia Universidad de Valencia, Valencia, Spain.
authors: Eva
authors: E
authors: Serna
authors: Facultad de Ciencias Biológicas, Universidad Complutense de Madrid, Madrid, España.
authors: Marta
authors: M
authors: Inglés
authors: Instituto Biodonostia, San Sebastian, Spain.
authors: Monica
authors: M
authors: de la Fuente
authors: IIKERBASQUE, Basque Foundation for Science, Bilbao, Spain.|Servicio de Geriatría. Hospital de la Ribera. Alzira, Valencia, Spain.
authors: Idoia
authors: I
authors: Garcia
authors: IIKERBASQUE, Basque Foundation for Science, Bilbao, Spain.|Servicio de Geriatría. Hospital de la Ribera. Alzira, Valencia, Spain.
authors: Ander
authors: A
authors: Matheu
authors: Dipartimento di Medicina Clinica e Sperimentale, Viale San Pietro 8, I-07100 Sassari, Italy.
authors: Paula
authors: P
authors: Sanchís
authors: Dipartimento di Medicina Clinica e Sperimentale, Viale San Pietro 8, I-07100 Sassari, Italy.
authors: Angel
authors: A
authors: Belenguer
authors: Instituto de Biomedicina de Valencia, IBV-CSIC, 46010 Valencia, Spain.
authors: Alessandra
authors: A
authors: Errigo
authors: Dipartimento di Medicina Clinica e Sperimentale, Viale San Pietro 8, I-07100 Sassari, Italy.
authors: Juan-Antonio
authors: JA
authors: Avellana
authors: Departamento de Geriatría. Hospital Universitario de Getafe, Madrid, Spain.
authors: Ana
authors: A
authors: Barettino
authors: Departamento de Geriatría. Hospital Universitario de Getafe, Madrid, Spain.
authors: Carla
authors: C
authors: Lloret-Fernández
authors: Departamento de Geriatría. Hospital Universitario de Getafe, Madrid, Spain.
authors: Nuria
authors: N
authors: Flames
authors: Instituto de Biomedicina de Valencia, IBV-CSIC, 46010 Valencia, Spain.
authors: Gianni
authors: G
authors: Pes
authors: Leocadio
authors: L
authors: Rodriguez-Mañas
authors: Facultad de Medicina, Universidad de Valencia, Valencia, Spain, INCLIVA and Spanish Centenarian Study Group; Facultad de Fisioterapia Universidad de Valencia, Valencia, Spain.
authors: Jose
authors: J
authors: Viña
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008136:Longevity / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C494811:BCL2L1 protein, human; D012333:RNA, Messenger; D051020:bcl-X Protein
keywords: Bcl-2; FAS ligand; RNA; apoptosis; healthy aging; longevity