Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging
Por:
Borras C, Abdelaziz KM, Gambini J, Serna E, Inglés M, de la Fuente M, Garcia I, Matheu A, Sanchís P, Belenguer A, Errigo A, Avellana JA, Barettino A, Lloret-Fernández C, Flames N, Pes G, Rodriguez-Mañas L and Viña J
Publicada:
1 dic 2016
Resumen:
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. elegans bearing a gain
of function mutation in the BcL-xL ortholog ced-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.
Filiaciones:
Borras C:
Facultad de Medicina, Universidad de Valencia, Valencia, Spain, INCLIVA and Spanish Centenarian Study Group
Facultad de Fisioterapia Universidad de Valencia, Valencia, Spain
Abdelaziz KM:
Facultad de Medicina, Universidad de Valencia, Valencia, Spain, INCLIVA and Spanish Centenarian Study Group
Facultad de Fisioterapia Universidad de Valencia, Valencia, Spain
Gambini J:
Facultad de Medicina, Universidad de Valencia, Valencia, Spain, INCLIVA and Spanish Centenarian Study Group
Facultad de Fisioterapia Universidad de Valencia, Valencia, Spain
Serna E:
Facultad de Medicina, Universidad de Valencia, Valencia, Spain, INCLIVA and Spanish Centenarian Study Group
Facultad de Fisioterapia Universidad de Valencia, Valencia, Spain
Inglés M:
Facultad de Ciencias Biológicas, Universidad Complutense de Madrid, Madrid, España
de la Fuente M:
Instituto Biodonostia, San Sebastian, Spain
:
IIKERBASQUE, Basque Foundation for Science, Bilbao, Spain
Servicio de Geriatría. Hospital de la Ribera. Alzira, Valencia, Spain
:
IIKERBASQUE, Basque Foundation for Science, Bilbao, Spain
Servicio de Geriatría. Hospital de la Ribera. Alzira, Valencia, Spain
Sanchís P:
Dipartimento di Medicina Clinica e Sperimentale, Viale San Pietro 8, I-07100 Sassari, Italy
Belenguer A:
Dipartimento di Medicina Clinica e Sperimentale, Viale San Pietro 8, I-07100 Sassari, Italy
Errigo A:
Instituto de Biomedicina de Valencia, IBV-CSIC, 46010 Valencia, Spain
Avellana JA:
Dipartimento di Medicina Clinica e Sperimentale, Viale San Pietro 8, I-07100 Sassari, Italy
Barettino A:
Departamento de Geriatría. Hospital Universitario de Getafe, Madrid, Spain
Lloret-Fernández C:
Departamento de Geriatría. Hospital Universitario de Getafe, Madrid, Spain
Flames N:
Departamento de Geriatría. Hospital Universitario de Getafe, Madrid, Spain
Pes G:
Instituto de Biomedicina de Valencia, IBV-CSIC, 46010 Valencia, Spain
Viña J:
Facultad de Medicina, Universidad de Valencia, Valencia, Spain, INCLIVA and Spanish Centenarian Study Group
Facultad de Fisioterapia Universidad de Valencia, Valencia, Spain
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