Researchers at the University of Bath’s Milner Centre and partners conducted a phylogenetic regression across 46 mammalian genomes. They identified 236 gene families whose size expansions correlate with maximum lifespan and brain size, notably enriched in immune functions—pointing to immune gene duplication as a driver of extended longevity.

Key points

• Comparative analysis across 46 mammalian genomes using PGLS identified 236 gene families expanding with MLSP.
• Relative brain size correlates with lifespan; 161 gene families link to both traits in dual-predictor models.
• Expanded gene families are enriched in immune-related GO categories: innate, adaptive, and inflammatory responses.
• MLSP-associated genes exhibit higher expression levels and alternative splicing potential in human data.
• No general increase in total protein-coding genes; body mass and other life-history traits do not explain expansions.
• Overlap found between MLSP-associated families and human longevity variants, indicating cross-species relevance.

Why it matters: These findings reveal immune gene duplication as an evolutionary mechanism linking brain development to extended lifespan in mammals. They shift focus from DNA repair alone to immune function in longevity evolution and may inspire targeted interventions to enhance immune resilience in aging.