RT Journal Article
T1 Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl‐xL in successful aging
A1 Borras, Consuelo
A1 Abdelaziz, Kheira M.
A1 Gambini, Juan
A1 Serna, Eva
A1 Inglés, Marta
A1 Fuente del Rey, Mónica de la
A1 García, Idoia
A1 Matheu, Ander
A1 Sanchís, Paula
A1 Belenguer, Ángel
A1 Errigo, Alessandra
A1 Avellana, Juan Antonio
A1 Barettino, Ana
A1 Lloret Fernández, Carla
A1 Flames, Nuria
A1 Pes, Gianni
A1 Rodriguez Mañas, Leocadio
A1 Viña, José
AB 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.
PB Aging
SN 1945-4589
YR 2016
FD 2016-10-28
LK https://hdl.handle.net/20.500.14352/17805
UL https://hdl.handle.net/20.500.14352/17805
LA eng
NO Ministerio de Educación y Ciencia (MEC)
NO Red Tematica de investigacion cooperative en envejecimiento y fragilidad (RETICEF) (España)
NO Consejería de Educación, Cultura y Deporte de la Generalitat Valenciana (España)
NO Consejería de Sanidad (Valencia, España)
NO FRAILOMIC-HEALTH
NO INCLIVA
NO FEDER
NO Marie Curie Career
DS Docta Complutense
RD 4 abr 2025