Fig. 3. The SenMayo gene set tracks genetic and pharmacologic clearance of senescent cells.

a The SenMayo panel successfully indicated aging in bone in mice (p value = 0.0023), n = 25 (12 young, 13 old (all ♀). Nominal p value, calculated as two-sided t-test, no adjustment since only one gene set was tested; b The elimination of p16^Ink4a-expressing senescent cells by AP20187 administration was shown previously to reverse the aging bone phenotype³⁷. The SenMayo gene set successfully demonstrated the significant reversal of the aging phenotype at the gene expression level upon the elimination of p16^Ink4a-expressing senescent cells (p = 0.0054), n = 29 (13 Veh, 16 AP (all ♀). Nominal p value, calculated as two-sided t-test, no adjustment since only one gene set was tested; c By specifically using the expression patterns of the SenMayo gene set, our bone RNA-seq revealed no similarities in gene expression patterns between young (blue) and old + veh (red) treated mice, and a substantial overlap of expression profiles of old + AP (green) mice with young mice. The highlighted genes represent variables, and the arrows drawn from the origin indicate their “weight” in different directions, according to the theories of Gabriel¹⁰³; d We used a previously published mRNA-seq dataset from human adipose tissue of our group^{24, 39}, to evaluate changes in SenMayo following D + Q treatment. Adipose tissue was collected before and 11 days after three days of oral D + Q treatment. Figure was designed using Biorender.com; e Using SenMayo, there was a reduction of SenMayo (p = 0.002) in the subcutaneous fat samples in the subjects treated with D + Q, consistent with a reduction in senescent cell burden following D + Q treatment (n = 9 (7 ♂, 2 ♀)). Nominal p value, calculated as two-sided t-test, no adjustment since only one gene set was tested. Source data are provided as a Source Data file.