Partial cellular reprogramming

This preclinical study examined whether transgenic expression of Δ133p53α, a senescence-inhibitory p53 isoform, alters inflammatory cytokines and chemokines in aging mice. Δ133p53α-expressing transgenic mice (both progeria model and naturally aged wild-type) showed reduced serum and tissue CXCL10 levels compared to controls, along with reductions in IL-6, CXCL1, and IL-1α. An inverse association between CXCL10 and Δ133p53α levels was also observed in human spleen tissue samples.

Researchers used a Markov generator-matrix model fitted to biomarker and mortality data from NHANES (n=23,512) and replicated in the Health and Retirement Study to test whether measured blood biomarkers account for, cause, and reverse with aging reversal. The analysis found that 92.7% of the Gompertz rise in mortality is assigned to a latent component not captured by measured biomarkers (89.1% under mean-field re-specification; 91.5% on replication). Mendelian-randomization analysis found known causal proteins but null results for inflammatory, renal, and growth-signalling markers. Cellular reprogramming reversed a chronological clock (−9.7 to −22.4 years) but not a damage clock enriched for causality.

This preclinical study investigated senescence-associated features in middle-aged female mice and human tissues, identifying an epigenetic upregulation of RBMX that increases splenic miR-10a-5p levels. The researchers found that miR-10a-5p can cross from the periphery to the brain, where it represses γCaMKII, influencing mitochondrial function, cellular senescence, and memory performance. In neurons from Alzheimer's disease patients and in model mice, inhibition of miR-10a-5p attenuated disease-associated phenotypes.

This systematic review examined pharmacological interventions targeting aging pathways, including metformin, from literature published January 2010–May 2026. Metformin and rapamycin had among the most extensive preclinical and translational evidence, but the review found that clinical evidence for broadly applicable geroprotection remains limited. The authors emphasize a substantial gap between mechanistic plausibility and clinically validated geroprotection in humans.