OP24 - Centenarians overexpress BCL-xL, which confers them a protection against apoptosis, oxidative stress and immunosenescence

Abstract

Centenarians not only have an extraordinary longevity, but also show a compression of morbidity. They preserve the capacity of maintaining homeostasis, and this is the reason for them to reach such a long life. We studied their mRNA expression profile and identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. A sub-network analysis showed six common genes: interferon, T-cell receptor, tumor necrosis factor, SP1 transcription factor, transforming growth factor and IL-32.These six centenarian-specific genes are related to Bcl-xL, Fas, and Fas ligand all of them involved in the control of apoptosis. RT-PCR analysis confirmed that centenarians up-regulate Bcl-xL. This is in keeping with the fact that they have lower plasma cytochrome C levels than septuagenarians. Bcl-xL is a mitochondrial protein involved not only in the control of apoptosis, but also in mitochondrial damage protection, control of mitochondrial respiration and immune response. We found that mitochondrial membrane potential (ΔΨm) as assessed by JC-1 cytometry was significantly higher in PBMCs obtained from centenarians versus septuagenarians as well as young people, suggesting that the functional state of mitochondria was maintained. Moreover, centenarians showed lower malondyaldhehyde and protein carbonyl levels than septuagenians. When analyzing the immune system, we found that leukocyte chemotaxis and NK cell activity were significantly impaired in septuagenarians compared with young people whereas in centenarians these indicators of immunosenescence were similar to the picture noted in young people. In conclusion, centenarians, who constitute an example of successful ageing, overexpress Bcl-xL, which confers them a protection against apoptosis, oxidative stress and immunosenescence. Supported by SAF2010-19498; SAF2013-44663-R; ISCIII2012-RED-43-029; PROMETEOII2014/056; RS2012-609; CM1001 and FRAILOMIC-HEALTH.2012.2.1.1-2. The study has been co-financed by FEDER funds from the European Union.