A consortium of longevity and immunology experts surveys recent advances in immunotherapies that selectively eliminate senescent cells. They detail CAR T strategies against uPAR and NKG2D ligands, senolytic vaccines targeting GPNMB or CD153, and PD-1/PD-L1 blockade, highlighting mechanisms and preclinical rejuvenation benefits.

Key points

• uPAR-directed CAR T cells safely eliminate uPAR+ senescent cells, reversing fibrosis and improving metabolism in mice.
• NKG2D-CAR T constructs recognize NKG2D ligands on stress-induced senescent cells, demonstrating efficacy in aged mice and nonhuman primates without off-target toxicity.
• PD-1/PD-L1 immune checkpoint blockade reduces PD-L1+ senescent cell accumulation and alleviates multiple age-related phenotypes via CD8+ T cell activation.

Why it matters: Immunotherapeutic senolytics promise targeted clearance of aging cells, offering safer, more durable rejuvenation therapies compared to conventional drugs.

A team from the National Research Lobachevsky State University of Nizhniy Novgorod alongside Longaevus Technologies LTD administers RepSox and tranylcypromine to aging C3H mice, finding enhanced neurological scores, improved skeletal health, and increased cortical angiogenesis via partial cellular reprogramming pathways, suggesting a promising anti-aging strategy.

Key points

• Intraperitoneal RepSox (5 mg/kg) plus TCP (3 mg/kg) every 72 h for 30 days in female C3H mice preserved fur density and skeletal posture.
• Neurological scores increased daily by 0.015 units in treated mice versus 0.018 in controls (p=0.002), reflecting slowed neurological aging.
• Survival analysis showed significant maximum lifespan extension (Gao-Allison p=0.039) and a reduced Gompertzian mortality slope (0.0034 vs. 0.0082 in controls).

Why it matters: This chemical reprogramming approach targets multiple aging hallmarks, offering a novel and potentially safer route to delay systemic aging and extend healthy lifespan.