Research Paper Volume 14, Issue 20 pp 8270—8291

Combining stem cell rejuvenation and senescence targeting to synergistically extend lifespan

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Figure 4. Cycling OKSM and Sen expression leads to lifespan and health span extension while combined OKSM-Sen expression increases both. (A) Survival curve for armGal4; tubGal80ts > UAS-TdTomato (TdTom), armGal4; tubGal80ts > UAS-OKSM (OKSM), armGal4; tubGal80ts > UAS-Sen (Sen) and armGal4; tubGal80ts > UAS-Sen; UAS-OKSM (Sen; OKSM) where expression was limited to one twelve-hour period twice per week through a temperature shift. At 25°C the temperature sensitive Gal80 protein ceases to inhibit Gal4 from driving expression from UAS enhancers, allowing for a targeted expression window when flies were shifted from 18°C to 25°C. Expression of OKSM, Sen and Sen; OKSM in adult female flies resulted in increased lifespan as compared to control flies (TdTom). Mean and maximum lifespans are shown along with corrected p-values. (B) Survival curve for the same experiment but with 24 hours of expression twice per week induced by a temperature shift of 18°C to 25°C. There were similar benefits of expression but reduced compared to the 12-hour expression experiment. Mean and maximum lifespans are shown along with corrected p-values. (C) Survival curve for flies expressing OKSM, Sen and Sen; OKSM but maintained at 25°C throughout their lifespans. The overall lifespans are shorter due to the higher temperature, but in addition all three experimental conditions show detriments to both mean and maximum lifespans. Mean and maximum lifespans are shown along with corrected p-values. A P-value of 0 reflects P < 1.0 * 10−10.