RNA Editing Genes Determine the Longevity of Human and Nematode

The (tumor suppressing) transcription factor "FOXO" is known to play the
key role in determining the life span of human and nematode. The kinase
cascade including LKB1 and AMPK activates FOXO, leading to the expansion
of life span, whereas the kinases AKT and PAK1 inactivate FOXO, leading
to the shortening of life span. There are several natural products that
both activate LKB1/AMPK and inactivate PAK1, leading to the expansion of
life span: CAPE (caffeic acid phenethyl ester) from Propolis, Curcumin
from Indian Curry, Capsaicin from Chili Pepper, Resveratrol from Red Grapes,
and Berberine. Thus, these products are among natural "Elixirs".

Recently, Paola Sebastiani's group at Boston University found that RNA editing
genes, ADR-1 and ADR-2, as well as RNA interfering gene RDE-1, also play
the key role in determining the life span of both human beings and nematodes
such as C. elegans. Dysfunction of RNA editing genes increases the RNA interfering activity of RDEs, and shortens the life span of nematode by 50%. Interestingly, however, dysfunction of RDE-1 gene could rescue the above (short-lived) nematode from the premature death. Thus, like the oncogenic kinases PAK1 and AKT, RDE-1 appears to shorten the life span by its RNA interfering activity (blocking the translation of its specific target genes which still remain to be identified).

Since Hsp16 (encoding a heat shock protein) is among the key genes downstream
of FOXO contributing to the expansion of life span, it is possible that
RDE-1 might block the translation of Hsp16 (or FOXO) RNA. We recently found that PAK1 blocks the expression of Hsp16 gene, and CAPE can re-activate Hsp16 gene
by inactivating PAK1. Also it would be of great interest to see if these natural elixirs activate ADRs or inactivate RDEs somehow.