Longevity Genes

Genetic variants influencing aging trajectory and disease risk.

10 entries

APOE
Apolipoprotein E gene with three common alleles (ε2/ε3/ε4) that dramatically alter lifetime Alzheimer's risk and lipoprotein metabolism. The most consequential single common variant in longevity genetics.
CETP
Cholesteryl ester transfer protein gene. Specific variants (particularly the I405V VV genotype) are over-represented in Ashkenazi centenarians and associate with lower CV risk and better cognitive aging.
FOXO3
Forkhead box O3 — the human ortholog of the C. elegans daf-16 longevity gene. Common variants in FOXO3 are among the most replicated genetic associations with extreme longevity across populations.
IGF1R
Insulin-like growth factor 1 receptor. Loss-of-function variants are over-represented in centenarian cohorts (especially Ashkenazi) — direct human evidence for the conserved insulin/IGF-1 lifespan-extension principle.
Klotho KL-VS Variant
A common Klotho haplotype (KL-VS) carried heterozygously by ~20–25% of Europeans. Associated with higher circulating Klotho, longer life expectancy, and modestly better cognition.
LPA Gene
Encodes apolipoprotein(a), the unique component of Lp(a) particles. LPA variants explain ~90% of inter-individual Lp(a) variation and confer lifelong cardiovascular risk modification.
MTHFR
Methylenetetrahydrofolate reductase. Two common variants (C677T, A1298C) modestly affect folate metabolism and homocysteine. Heavily over-marketed in functional medicine; effects on hard outcomes are smaller than often claimed.
SIRT6
Nuclear sirtuin maintaining telomere integrity, repressing LINE-1 retrotransposons, and supporting genome stability. SIRT6 overexpression extends mouse male lifespan; loss-of-function causes progeroid phenotype.
SOD2
Mitochondrial manganese superoxide dismutase — the primary defense against superoxide produced by oxidative phosphorylation. A common variant (V16A) affects mitochondrial import efficiency and modestly modulates aging-related disease risk.
TERT
Telomerase reverse transcriptase. Loss-of-function variants cause severe telomere-biology disorders with premature aging. Hyperactive variants drive cancer. The tightest known longevity-cancer trade-off.