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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. [ABSTRACT FROM AUTHOR]

The in vitro culture is routinely carried out under ambient oxygen tension. However, in vivo human Dental Pulp Stem Cells (hDPSC) are not exposed to such hyperoxic conditions. Dental pulp tissue physiological oxygen tension ranges between values of 3% to 6% O 2 . In vitro cellular senescence refers to both replicative and premature senescence. Replicative senescence is associated with a progressive increase in the expression of p16 INK4a . Bmi-1 is a supresor of p14 ARF and p16 INK4a . Premature or accelerated senescence can be induced by ROS accumulation. It has been demonstrated that pluripotency can be induced by introducing 2 factors: Sox2 and Oct4. The aim of this study was to investigate the involvement of oxidative stress induced by culture under 21% oxygen, in the maintenance of pluripotency and in the mechanisms of chronological and premature aging of hDPSC. hDPSC cultured under 21% O 2 showed dihydrorhodamine levels significantly higher, and their mitocondrial membrane potential was lower in comparison to hDPSC cultured under 21% O 2 . Bmi-1 expression increases with passages, but this expression is higher in hDPSC cultured under 21% O 2 in comparison to 3% O 2 since the beginning. At early passages, Sox2 and Oct4 are overexpressed when culture under 3% O 2 compared to 21% O 2 , and its expression decreases with passages. p14 ARF , p16 INK4a expression and beta-Galactosidase activity remain very low in hDPSC cultured under 3% O 2 , whereas under 21% O 2 they are significatively augmented. p21 expression increases with passages under both 3% or 21% O 2 culture conditions. Because hDPSC expressed p14 ARF and p16 INK4a but not Bmi-1 or p21, we conclude that in vitro premature senescence under 21% O 2 may be associated with oxidative stress and not with Bmi-1 overexpression. hDPSC culture under 3% O 2 mantains its stemness and reduces premature senescence. 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. [ABSTRACT FROM AUTHOR]