Doubling healthy lifespan using drug synergy

Tesfahun Dessale; Krishna Chaithanya Batchu; Diogo Barardo; Ng Li Fang; Vanessa Yuk Man Lam; Linfan Xiao; Markus R. Wenk; Nicholas S. Tolwinski; Jan Gruber

257 Surprisingly, animals treated with RAP+RIF+ALLAN and RIF+PSORA+ALLAN also performed 258 significantly better in the spontaneous movement assay than control animals at most ages. In fact, old 259 treated animals (day 18 of age) showed performance in this assay that was indistinguishable from 260 young (day 7) controls ( Fig. 5g) . Moreover, treated animals experienced improvements in resistance 261 to heat and oxidative stress (paraquat) assays, (Figure 5e The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/153205 doi: bioRxiv preprint 8 limited detected tradeoffs, but also improved health span, increased stress resistance, and even 264 increased physical performance. Such observations raise the important question if these lifespan 265 benefits are due to an actual delay in biological ageing rate. The rate of ageing can be expressed as 266 mortality rate doubling time (MRDT). We determined MRDT of animals exposed to synergistic drug 267 combinations using Survcurv 53 , and found MRDT to be significantly longer in RIF+PSORA+ALLAN 268 treated animals compared to controls (MRDT of control = 3 days and RIF+PSORA+ALLAN = 3.7 269 days, P value < 0.0001). The initial mortality rate was significantly lower for both synergistic should be noted that cohort size of flies was smaller than for worms and that we did not re-optimize 294 drugs for the fly experiments. However, these data confirms that some of the detected synergies 295 appear to be evolutionary conserved.