UK study confirms healthy habits can extend lifespan, even with genetic predispositions

By Pooja Toshniwal PahariaReviewed by Lily Ramsey, LLMApr 29 2024

In a recent study published in BMJ Evidence-Based Medicine, researchers investigated the associations between lifestyle, genetic factors, and human longevity.

Study: Genetic predisposition, modifiable lifestyles, and their joint effects on human lifespan: evidence from multiple cohort studies. Image Credit: muse studio/Shutterstock.com

Background

Hereditary and non-hereditary variables, such as lifestyle activities, influence the human lifespan. The apolipoprotein E (APOE) gene and the low-density lipoprotein receptor (LDLR), Nicotinic Acetylcholine Receptor 3/5 (CHRNA 3/5), Lipoprotein A (LPA), and Cyclin-dependent Kinase Inhibitors 2B Antisense RNA 1 (CDKN2B-AS1) loci are related to longevity.

Excessive alcohol intake, chronic tobacco use, prolonged physical inactivity, and unhealthy dietary habits contribute to premature mortality.

Studies have reported negative relationships between body obesity, smoking, coronary heart disease susceptibility, and a longer lifetime.

A health-conscious lifestyle may reduce genetic vulnerability to a shortened lifespan; however, further research could clarify the combined impact of genetic variables and lifestyle choices.

About the study

In the present longitudinal cohort study, researchers explored the influence of lifestyle and genetic factors on human longevity.

The team analyzed the United States National Health and Nutrition Examination Survey (NHANES), the United Kingdom Biobank, and LifeGen data to calculate polygenic risk scores (PRS) for genetic susceptibilities related to human longevity, evaluate the impact of lifestyle habits, and examine the joint associations of genetic determinants and lifestyle variables on human longevity.

Lifestyle variables included alcohol intake, smoking, physical activity, diet, sleep duration, and body shape.

The study included 353,742 European adults recruited between 2006 and 2010 and followed up through 2021. The study exposure included the longevity PRS with the uppermost quintile categories and the healthy lifestyle score (HLS).

No smoking, regular physical exercise, moderate alcohol intake, nutritious diet, healthy body form, and adequate sleep indicate a healthy lifestyle. The researchers determined lifespan, the primary outcome, based on the death date or summing-up age at study initiation and follow-up.

The researchers derived the PRS using independent hereditary variants associated with lifespan, as captured by LifeGen data, with no linkage disequilibrium. They determined the PRS for UK biobank individuals using the weighted sum of lifespan-reducing alleles for single nucleotide polymorphisms (SNPs) multiplied by their effect sizes on longevity.

The team performed Cox proportional hazards regression modeling using NHANES data to determine hazard ratios (HR) for the impact of lifestyle factors on lifespan, applying the findings to UK Biobank data to calculate the weighted HLS.

They used multivariate logistic regressions to determine the relationships between the PRS and lifestyle factors, adjusting for age, sex, educational attainment, and socioeconomic status.

The researchers analyzed death records in the US NHANES and UK Biobank, censoring data for survivors' lifespans on December 31, 2021, excluding deaths related to injuries, accidents, or coronavirus disease 2019 (COVID-19). The National Center for Health Statistics (NCHS) linked death certificates to December 31, 2019.

Results

Among the 353,742 Europeans followed up for 13 years (median), 24,239 deaths occurred. The researchers grouped participants by their genetically estimated lifespan into the short (20%), intermediate (60%), and long (20%) lifespan groups and by HLS into the unfavorable (21%), intermediate (56%), and favorable (23%) lifestyle groups.

A high genetic risk was associated with a 21% higher chance of mortality than a low genetic risk, regardless of lifestyle circumstances.

Genetic and behavioral variables showed independent relationships with longevity. Individuals genetically predisposed to a short lifetime (high PRS) had a hazard ratio (HR) of mortality 1.2 higher than that of individuals with higher longevity.
Individuals with unfavorable lifestyles (low HLS) had a 1.8-fold higher risk of mortality than those with favorable lives. Individuals with lower longevity and unfavorable lifestyles had 2.0 times the death rate as those with higher longevity and favorable lifestyles.

The researchers found no multiplicative interactions between the PRS and HLS.  The best combination for a healthy lifestyle includes regular physical exercise, healthy eating habits, no smoking, and appropriate sleep, reducing premature mortality risk (death before the age of 75 years).

Individuals genetically sensitive to longer lifespans and following favorable lifestyles had a life expectancy of 53 years at 40 years, compared to 46 years for those with genetic propensities for a short lifespan and unfavorable lifestyles. The ideal lifestyle for a long life includes frequent physical exercise, no smoking, a good diet, and enough sleep.

The study findings showed that healthy lifestyle practices can considerably minimize the hereditary risk of a reduced lifespan or untimely death. A high hereditary risk was associated with a 21% greater chance of mortality, but an unhealthy lifestyle was associated with a 78% increase.

Healthy lifestyle habits can reduce the hereditary risk by 62%. Participants with a genetic tendency toward low life expectancy and an unhealthy lifestyle had a 2.04 times greater mortality risk.

Healthy lifestyle practices may significantly reduce the loss of life for people with a shorter lifespan. Future research should include non-European participants to improve generalizability.