Gene
CETP
Last updated 2026-05-30· 1 min read
Reviewed by the Ultimate Longevity Bible editorial team. Educational reference — not medical advice. See disclaimer.
Why it matters
CETP regulates the exchange of cholesteryl esters between HDL and apoB-containing particles. Reduced CETP activity (from the VV genotype at codon 405) produces higher HDL, larger HDL particles, and is associated with:
- Lower cardiovascular event rates.
- Better cognitive aging.
- Lower dementia incidence.
- Over-representation in Ashkenazi centenarians (Nir Barzilai's Longevity Genes Project).
The CETP-inhibitor drug story
The "lower CETP = better" hypothesis drove decades of drug development:
- Torcetrapib (Pfizer): cardiovascular harm; programme terminated.
- Dalcetrapib (Roche): neutral.
- Evacetrapib (Lilly): neutral.
- Anacetrapib (Merck): modest benefit; programme halted on commercial grounds.
- Obicetrapib (NewAmsterdam Pharma): newer, more potent; trials ongoing.
The mixed results suggest that "lifelong" CETP reduction (genetic) may produce different outcomes than late-life pharmacological reduction.
Caveat about Mendelian randomization
Mendelian-randomization analyses suggest the CETP-longevity association may partly reflect linked variants (linkage disequilibrium) rather than CETP function alone. The story is more nuanced than the original single-variant interpretation.
- FOXO3 — Gene.
- IGF1R — Gene.
- Klotho KL-VS Variant — Gene.
- Best Supplements for Longevity (Evidence-Backed Only) — Best-of guide.
- IGF-1 (Insulin-Like Growth Factor 1) — Biomarker.
Related entries
References
- Barzilai, N. et al. Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 290, 2030–2040 (2003).