Breakthrough in Lifespan Genetics: Correcting the Record on Heritability

A groundbreaking study published in the prestigious journal Science has upended long-held assumptions about the genetic influence on human lifespan. Researchers led by Ben Shenhar from the Weizmann Institute of Science in Israel reveal that the heritability of intrinsic human lifespan—deaths due to biological aging processes rather than external factors like accidents or infections—stands at approximately 50 to 55 percent. This figure more than doubles previous estimates derived from twin studies, which hovered around 20 to 25 percent. The findings, which garnered major coverage in New Zealand media including Radio New Zealand (RNZ), underscore the potential for genetics to play a pivotal role in unraveling the mysteries of aging and longevity.

Heritability, defined here as the proportion of variation in a trait attributable to genetic differences among individuals in a specific population and environment, has been a contentious topic in longevity research. Traditional analyses often lumped all causes of death together, obscuring the genetic signals buried under extrinsic mortality noise. By employing sophisticated mathematical modeling—partitioning mortality into intrinsic (age-dependent biological failure) and extrinsic (constant hazard from outside causes)—the team corrected for these confounders, yielding a clearer picture of genetic contributions.

This correction is crucial because historical twin cohorts, primarily from Denmark and Sweden born in the late 19th and early 20th centuries, faced high extrinsic risks like infectious diseases before antibiotics. One twin might die at 30 from cholera, masking familial longevity patterns. Modern datasets with lower extrinsic mortality show heritability rising accordingly, aligning with patterns in other complex traits like height or blood pressure.

Decoding the Methods: Twin Studies and Mortality Modeling

The study's methodology hinges on classic twin designs: monozygotic (identical) twins share nearly 100 percent of their genes, while dizygotic (fraternal) twins share about 50 percent, akin to regular siblings. Heritability is calculated using Falconer's formula: h² = 2(r_MZ - r_DZ), where r represents lifespan correlations. Uncorrected data from Danish twins yielded h² ≈ 0.23; Swedish ≈ 0.35; and the Swedish Adoption/Twin Study of Aging (SATSA) ≈ 0.33.

• Mathematical partitioning: Modeled mortality as Gompertz-Makeham (exponential intrinsic + constant extrinsic) or saturating-removal, simulating genetic variation in parameters like aging rate or threshold.
• Extrinsic correction: Setting extrinsic mortality m_ex to 0 doubled correlations from ~0.23 to ~0.50, boosting h² to ~0.55.
• Cutoff age adjustment: Excluding deaths before age 15 mildly nonlinearly affects estimates, optimized for modern low-m_ex contexts.
• Validation: SATSA cause-specific data (cancer h²~0.3, cardiovascular ~0.5, dementia ~0.7) and US centenarian siblings confirmed ~50-61 percent.

These steps reveal 'heritability of intrinsic lifespan' (HIL) at 55 percent ±1 percent, robust across models and cohorts. Code and data are openly available on Zenodo, inviting replication.

Why Previous Estimates Fell Short: Confounders Exposed

Prior skepticism stemmed from low heritability figures, discouraging genetic hunts for aging genes. Pedigree studies even suggested as low as 6 percent. Yet, simulations show extrinsic mortality compresses lifespan variance, reducing twin correlations. In high-m_ex eras, it disproportionately affects shorter-lived relatives, diluting signals. Mortality compression (lifespans bunching near maximum) has negligible impact (~2 percent decline).

Cutoff age nonlinearity arises because early extrinsic deaths skew DZ more than MZ pairs under certain models. The study also notes heritability's context-dependency: not fixed like gravity, but population-specific. This aligns human intrinsic lifespan with mouse studies (38-55 percent) and average human traits (49 percent).

For New Zealand researchers, this methodological toolkit offers a blueprint to reanalyze local longitudinal data, potentially uncovering population-specific insights.

Major NZ Media Spotlight: RNZ Leads the Conversation

Radio New Zealand's coverage highlighted the study's paradigm shift, noting genetics now explain half of lifespan variation under ideal conditions—double past views and matching lab animals. RNZ emphasized how extrinsic factors like pre-antibiotic infections confounded old data, validated by twins raised apart (genes sans shared environment). This 'major' attention reflects Kiwi interest in science that touches universal concerns: how to add healthy years.

While the study used Scandinavian and US data, NZ's robust longitudinal cohorts position local universities to contribute. Scimex echoed expert reactions: "over half of how long we live is inherited," urging caution on interpretations.

Read the full Science paper for technical depth.

New Zealand's Strong Foundation in Lifespan and Genetics Research

New Zealand universities are at the forefront of lifespan science, complementing this global breakthrough. The University of Otago's Lifespan Research cluster integrates full lifecourse perspectives via the iconic Dunedin Multidisciplinary Health and Development Study—a 1972-73 birth cohort tracked to midlife, pioneering biological aging metrics like DunedinPACE, a DNA methylation 'speedometer' for aging pace.

• DunedinPACE: Tracks morbidity, disability, mortality; higher pace predicts faster aging in young adults.
• Genetics Otago: World-class hub spanning health, tech; neuroendocrinology probes hormonal aging influences.
• Christchurch Health and Development Study: 40+ years on 1,265 cohort, linking early life to longevity.

University of Auckland's Liggins Institute focuses on lifelong health determinants from conception, including nutrition's lifespan impacts. Recent stem cell work suggests female longevity edges via better muscle regeneration. These assets position NZ for heritability-informed studies, perhaps integrating polygenic risk scores with local Māori/Pacific data for equitable insights.

Cause-Specific Insights: Dementia Tops Genetic Influence

The SATSA analysis breaks down by cause: dementia heritability peaks at 70 percent up to age 80 (declining later), cardiovascular at 50 percent, cancer steady at 30 percent. This guides targeted research—dementia genetics early, cancer universally.

In NZ, where dementia burdens ageing populations, Otago's CARE (Collaboration on Ageing Research Excellence) and Ageing Well National Science Challenge can leverage these findings. Imagine applying HIL corrections to Dunedin data for NZ-specific rates.

Protective genes in centenarians—hundreds potentially—hint at bidirectional effects: harmful variants shorten, beneficial extend life without disease.

Implications for Aging Research and Public Health

High heritability validates pursuing longevity genes, revealing mechanisms like cellular senescence or DNA repair. Bidirectional GWAS (genome-wide association studies) could identify targets for therapies—mimicking centenarian protections.

Remaining 45 percent? Environment (lifestyle, SES), epigenetics, stochasticity. Twin designs dissect these. For NZ, with excellent healthcare compressing mortality, intrinsic genetics shine brighter today than a century ago.

This boosts funding prospects; low past h² deterred grants. Now, interdisciplinary teams—physicists like Shenhar modeling biologists—pave ways.

Career Opportunities in NZ Higher Education Genetics

This study spotlights booming demand for genetics experts in universities. NZ institutions seek researchers in longevity genomics, bioinformatics for twin data, epigenetic clocks. Research jobs at Otago or Auckland offer chances to build on Dunedin legacies, collaborate internationally.

Postdocs, lecturers in human genetics (higher-ed postdoc jobs) thrive amid global aging focus. NZ university jobs emphasize diverse cohorts, addressing Māori health disparities via heritability lenses. Aspiring academics, check career advice for success.

Future Outlook: Gene Hunts and Lifespan Extension

Next: Low extrinsic-mortality cohorts, full cause-of-death integration, nonadditive genetics. NZ's clean environment suits 'ideal' HIL tests. Ethical gene editing (CRISPR) looms, but first, understand variants.

Societally, balanced view: genes set potential, lifestyle unlocks. NZ's active ageing ethos—not smoking, social ties—complements genetics.

Photo by Christian Chomiak on Unsplash

Wrapping Up: A Genetic Revolution in Longevity Science

The 50 percent heritability revelation reframes aging as genetically tractable, exciting for researchers and hopeful for healthier lifespans. NZ universities, with world-class cohorts and coverage, are primed to lead. Explore professor insights via Rate My Professor, pursue higher ed jobs, or advance your career with higher ed career advice. University jobs await in this vibrant field—post a job to attract top talent.