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

被引：41

作者：

Borras, Consuelo ^{[1
,2
]}

Abdelaziz, Kheira M. ^{[1
,2
]}

Gambini, Juan ^{[1
,2
]}

Serna, Eva ^{[1
,2
]}

Ingles, Marta ^{[3
]}

de la Fuente, Monica ^{[4
]}

Garcia, Idoia ^{[5
,6
]}

Matheu, Ander ^{[5
,6
]}

Sanchis, Paula ^{[7
]}

Belenguer, Angel ^{[7
]}

Errigo, Alessandra ^{[8
]}

Avellana, Juan-Antonio ^{[7
]}

Barettino, Ana ^{[9
]}

Lloret-Fernandez, Carla ^{[9
]}

Flames, Nuria ^{[9
]}

Pes, Gianni ^{[8
]}

Rodriguez-Manas, Leocadio ^{[10
]}

Vina, Jose ^{[1
,2
]}

机构：

[1] Univ Valencia, Fac Med, INCLIVA, Valencia, Spain

[2] Spanish Centenarian Study Grp, Valencia, Spain

[3] Univ Valencia, Fac Fis, Valencia, Spain

[4] Univ Complutense Madrid, Fac Ciencias Biol, Madrid, Spain

[5] Inst Biodonostia, San Sebastian, Spain

[6] Basque Fdn Sci, IIKERBASQUE, Bilbao, Spain

[7] Hosp Ribera Alzira, Serv Geriatr, Valencia, Spain

[8] Dipartimento Med Clin & Sperimentale, Viale San Pietro 8, I-07100 Sassari, Italy

[9] CSIC, IBV, E-46010 Valencia, Spain

[10] Hosp Univ Getafe, Dept Geriatr, Madrid, Spain

来源：

AGING-US | 2016年 / 8卷 / 12期

关键词：

healthy aging; apoptosis; Bcl-2; FAS ligand; longevity; RNA; CELL-DEATH; OXIDATIVE DAMAGE; CAENORHABDITIS-ELEGANS; GLUTATHIONE OXIDATION; MITOCHONDRIAL-DNA; IN-VIVO; APOPTOSIS; PROTEINS; BCL-X(L); SURVIVAL;

D O I：

10.18632/aging.101078

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：3185 / +

页数：24

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