Skip to main content
. 2021 Jul 15;2:708680. doi: 10.3389/fragi.2021.708680

FIGURE 4.

FIGURE 4

In vivo screening in humans for drugs associated with decelerated aging identifies geroprotector doxazosin. (A) Schematic to demonstrate use of pharmaceuticals may promote healthy aging or “rejuvenate” from a state of accelerated aging (black) to a state of decelerated aging (blue). (B) Number of drugs taken per person, for each decade of life, in the NHANES 2005–2006 dataset. (C) Volcano plot including all drugs from all users over the age of 70, whereby the x-axis is the median change in deltaAges of users of any given drug, relative to non-users, and the y-axis is the significance of this difference (−log10 p-value, Kolmogorov-Smirnov test). Dashed lines correspond to p < 0.05 and p < 0.01. (D) Based on panel C, drugs ranked by their decelerating or accelerating effect on aging. Rank is given to each drug by multiplying their log10 p value by the sign of deltaAge (negative or positive). (E) The top compounds from panels C and D associated with either accelerated or decelerated aging. Only one compound is significant at p < 0.01: doxazosin. (F) The distribution of deltaAges of doxazosin users relative to all individuals (depicting top result from panel C). Density plot overlaid on top of histogram (n = 10 for doxazosin and 1922 for all other drugs). (G) Mobility as determined by crawling speed on day 9 of life, for C. elegans grown on DMSO control (0.2%), or 33 μM doxazosin. Worms treated with doxazosin are significantly more mobile than untreated (n = ∼80–130 worms per condition, p < 0.001, Mann-Whitney U Test). Replicates and statistics of mobility experiments can be found in Supplementary Table 3. (H) Survival curves showing that 3.3 μM doxazosin, extends lifespan in wild type (N2) C. elegans (n = ∼450 worms per condition, p < 0.0001, Log-rank test). Results are pooled from three independent experiments. Individual replicates and statistics can be found in Supplementary Table 4. (I) Worm activity healthspan as measured by motility on days 2, 5, 9, and 12 of adulthood. On days 9 and 12, the percentage of highly active worms is significantly higher for the population treated with 3.3 μM doxazosin (n = 18 videos analyzed per condition, p < 0.05, Two-way ANOVA). Results represent pooled data from three independent experiments. Individual replicates and statistics of motility experiments can be found in Supplementary Table 5.