Journal
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
Volume 72, Issue 8, Pages 1024-1032Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glw153
Keywords
AFT model; Longevity; NNT; mTOR; Proportional hazard
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Rapamycin has favorable effects on aging in mice and may eventually be applied to encourage healthy aging in humans. This study analyzed raw data from 29 survival studies of rapamycin-and control-treated mice, with the goals of estimating summary statistics and identifying factors associated with effect size heterogeneity. Meta-analysis demonstrated significant heterogeneity across studies, with hazard ratio (HR) estimates ranging from 0.22 (95% confidence interval [CI]: 0.06-0.82) to 0.92 (95% CI: 0.65-1.28). Sex was the major factor accounting for effect size variation, and mortality was decreased more in females (HR = 0.41; 95% CI: 0.35-0.48) as compared with males (HR = 0.63; 95% CI: 0.55-0.71). Rapamycin effects were also genotype dependent, however, with stronger survivorship increases in hybrid mice (14.4%; 95% CI: 12.5-16.3%) relative to pure inbred strains (8.8%; 95% CI: 6.2-11.6%). Number needed to treat was applied as an effect size metric, which consistently identified early senescence as the age of peak treatment benefit. These results provide synthesis of existing data to support the potential translation of findings from mouse to primate species. Because rapamycin's effect on survival depends on sex and genotype, further work is justified to understand how these factors shape treatment response.
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