24 páginas, 7 figuras. Borras C, et al. Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging. Aging (Albany NY). 2016 Oct 28;8(12):3185-3208. doi: 10.18632/aging.101078. ; 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. ; This work was supported by grants SAF2013-44663-R, from the Spanish Ministry of Education and Science (MEC); ISCIII2012-RED-43-029 from the “Red Tematica de investigacion cooperative en envejecimiento y fragilidad” (RETICEF); PROMETEOII/2014/056 from "Conselleria d’Educació, Cultura I Esport de la Generalitat Valenciana"; and EU Funded CM1001 and FRAILOMIC-HEALTH.2012.2.1.1-2 (To J.V) APM-03/15 from Conselleria de Sanitat, AICO/2016/067 and from Conselleria d’Educació, Cultura i Esport de la Generalitat Valenciana, Intramural Grant from INCLIVA (to C.B.),VAL i+d Fellowship from Generalitat Valenciana (to C.L.-F.) and Marie Curie Career Integration Grant (to N.F). This study has been co-financed by FEDER funds from the European Union. ; Peer reviewed