The data presented in this open access paper provides a good example of the complexity of the metabolic processes that influence life span. The researchers overexpress the UPD1 gene in various different tissues in flies. While the UPD1 protein acts via the JAK/STAT pathway in each case, the results on fly life span are wildly different. This sort of thing is exactly why it is very challenging, very slow, and very expensive to try to even modestly slow aging by tinkering with the operation of metabolism, to make an organism more resilient to the damage of aging. There are far better ways forward than this, notably those that involve periodic repair of the damage of aging.
The JAK/STAT signaling pathway is involved in many aging-related cellular functions. However, effects of overexpression of genes controlling JAK/STAT signal transduction on longevity of model organisms have not been studied. Here we evaluate the effect of overexpression of the unpaired 1 (upd1) gene, which encodes an activating ligand for JAK/STAT pathway, on the lifespan of Drosophila melanogaster.
Overexpression of upd1 in the intestine caused a pronounced shortening of the median lifespan by 54.1% in males and 18.9% in females, and the age of 90% mortality by 40.9% in males and 19.1% in females. In fat body and in nervous system of male flies, an induction of upd1 overexpression increased the age of 90% mortality and median lifespan, respectively. An increase in upd1 expression enhanced mRNA levels of the JAK/STAT target genes domeless and Socs36E.
Conditional overexpression of upd1 in different tissues of Drosophila induces pro-aging or pro-longevity effects in tissue-dependent manner. The effects of upd1 overexpression on lifespan are accompanied by the transcription activation of genes for the components of JAK/STAT pathway. As the JAK/STAT pathway is evolutionarily conserved it may be possible to discover compounds that fit the criteria of geroprotector. In our future work we plan to test the compounds from DrugAge and geroprotectors.org and other libraries potentially modulating upd, domeless and Socs36E on the lifespan of Drosophila and other organisms.