Universidad Complutense de Madrid
E-Prints Complutense

Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl‐xL in successful aging

Impacto

Downloads

Downloads per month over past year

Borras, Consuelo and Abdelaziz, Kheira M. and Gambini, Juan and Serna, Eva and Inglés, Marta and Fuente del Rey, Mónica de la and García, Idoia and Matheu, Ander and Sanchís, Paula and Belenguer, Ángel and Errigo, Alessandra and Avellana, Juan Antonio and Barettino, Ana and Lloret Fernández, Carla and Flames, Nuria and Pes, Gianni and Rodriguez Mañas, Leocadio and Viña, José (2016) Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl‐xL in successful aging. Aging, 8 (12). pp. 3185-3201. ISSN 1945-4589

[img]
Preview
PDF
Creative Commons Attribution.

7MB

Official URL: http://www.aging-us.com/article/101078



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. 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.


Item Type:Article
Uncontrolled Keywords:Healthy aging, apoptosis, Bcl-2, FAS ligand, longevity, RNA
Subjects:Medical sciences > Biology
Medical sciences > Biology > Genetics
ID Code:42770
Deposited On:16 May 2017 17:30
Last Modified:18 May 2017 07:49

Origin of downloads

Repository Staff Only: item control page