Longevity and survival factors implicated in human ageing and longevity
E.S. Gonos
National Hellenic Research Foundation, Institute of Biological Research and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece
We have developed conditionally immortalized cell lines and we have
cloned several senescence associated genes. Analysis of the function of
one of the isolated genes (ApoJ), suggests that it is a novel survival
factor. ApoJ is found over-expressed in vitro under a variety of stress
conditions and in vivo in patients suffering from various age-related
diseases. Stable over-expression of ApoJ inhibits apoptosis and its
inhibition by RNA interference sensitizes cells to cytotoxicity.
Moreover, we have shown that ApoJ is implicated to DNA repair processes
as it interacts with the DNA helicases Ku70/80. We have also studied
proteasome function in replicative senescence and cell survival. We
have observed reduced levels of proteasomal peptidase activities in
senescent cells that is accompanied by a decrease in the level of both
20S and 26S complexes. Partial inhibition of proteasomes in young cells
caused by treatment with specific inhibitors induced a senescence-like
phenotype and stable over-expression of beta-1 and beta-5 subunits in
established cell lines was shown to induce elevated expression levels
of beta-1 subunit in beta-5 transfectants and vice-versa. Transfectants
possess increased proteasome activities and most importantly, increased
capacity to cope better with various stresses.
Key words:
human, longevity, proteasome, senescence, survival
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