Heritability of intrinsic human life span is about 50% when confounding factors are addressed.

Current estimates of life span heritability are confounded by extrinsic mortality, leading to underestimates.

• Twin studies currently show heritability of only 20 to 25% for human life span.
• Recent large pedigree studies suggest heritability is as low as 6%.
• Extrinsic mortality refers to deaths caused by extrinsic factors such as accidents or infections.
• The authors argue these low estimates are artifacts of including extrinsic mortality in analyses.

Heritability of human life span due to intrinsic mortality is above 50% after correcting for extrinsic mortality.

• The corrected heritability estimate exceeds 50%.
• This was determined using mathematical modeling combined with analyses of twin cohorts.
• Both twins raised together and twins raised apart were analyzed to disentangle genetic from shared environmental effects.
• This estimate is similar to heritability of most other complex human traits.

The corrected intrinsic life span heritability is comparable to life-span heritability in other species.

• The authors note that heritability above 50% aligns with life-span heritability observed in other species.
• This consistency across species supports the validity of the corrected estimate.
• The finding implies that previous low heritability estimates in humans were anomalously low due to confounding.

Mathematical modeling was used to quantify the diluting effect of extrinsic mortality on observed heritability estimates.

• The authors developed a mathematical model to separate intrinsic from extrinsic causes of death.
• Twin cohort data from twins raised together and apart were used to empirically validate and apply the model.
• The model demonstrates that extrinsic deaths reduce the observed genetic signal in life span data.
• Correcting for this confound substantially increases the heritability estimate.

High heritability of intrinsic life span suggests that longevity genes can reveal aging mechanisms and inform medicine and public health.

• The authors argue that if genetic heritability is high, longevity genes are more tractable targets for understanding aging.
• High heritability supports the potential for genetic studies to inform public health interventions.
• This finding reframes the genetic basis of human longevity as comparable to other well-studied complex traits.