Combining stem cells rejuvenation with senescence-targeting to extend lifespan
We designed a Drosophila model that combined senolytic removal and cellular reprograming. We first used the OKSM approach based on four Yamanaka factors, as it had previously been shown to induce stem cells from non-mammalian vertebrate or invertebrate animals and mammals [32]. We used the mouse sequence (FOXO4 – DRI [22]) in order to design a Drosophila orthologous peptide that was based on Drosophila’s foxo gene (forkhead, sub-group O). The effects of the two interventions were then assessed, both individually and in combination.
We started by looking at the effects of OKSM on stem cells using an intestinal stem cell model (ISC). We decided to examine phenotypic changes in the digestive system Drosophila. (Supplementary figure 1). Drosophila has a similar gastric lining to mammals. This is due to stem cells that replace the epithelia. Drosophila’s age-dependent decline in function and mortality is attributed to the loss of stem cells with age and to the degradation of barrier functions [36]. Drosophila’s gut is made up of four types of cells: enterocytes, enteroendocrine cells (EEs), enteroblasts and intestinal stem cells.
Source:
https://www.aging-us.com/article/204347/text
