Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice.

Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice receiving both drugs was neither higher nor lower than that seen previously in Rapa only, perhaps reflecting the limited survival benefits seen in prior cohorts of females receiving Aca alone. Capt led to a significant, though small (4% or 5%), increase in female lifespan. Capt also showed some possible benefits in male mice, but the interpretation was complicated by the unusually low survival of controls at one of the three test sites. BD seemed to produce a small (2%) increase in females, but only if the analysis included data from the site with unusually short-lived controls. None of the other 4 tested agents led to any lifespan benefit. The C2017 ITP dataset shows that combinations of anti-aging drugs may have effects that surpass the benefits produced by either drug used alone, and that additional studies of captopril, over a wider range of doses, are likely to be rewarding

Beta-guanidinopropionic acid does not extend Drosophila lifespan

Activation of AMP activated protein kinase (AMPK) signaling has been demonstrated to extend lifespan and improve healthspan across multiple species. This suggests pharmaceutical approaches to increase AMPK hold the potential to modify the aging process and promote healthy aging. Beta-guanidinopropionic acid (GPA) is a naturally occurring metabolite structurally similar to creatine. GPA is capable of activating AMPK signaling in mammalian models via competitive inhibition of cytosolic creatine kinase. A previous report suggested that dietary GPA supplementation increased lifespan in Drosophila through its effect on AMPK signaling and regulation of autophagy. However, studies in Caenorhabditis have found no beneficial effect of this compound on worm lifespan and that GPA may actually diminish lifespan in at least one Caenorhabditis species. To confirm previous reports of increased longevity in Drosophila, we tested a wide range of GPA concentrations on lifespan and healthspan in both male and female W1118 flies. We report here that GPA does not extend lifespan in Drosophila as previously reported. Moreover, high doses of GPA are detrimental to Drosophila lifespan and stress resistance in male flies. These results suggest the lack of a robust effect of GPA on Drosophila lifespan and highlight the importance of replication studies within the field of aging