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Modifiable pathways for longevity: A Mendelian randomization analysis.

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This study investigated factors influencing longevity, finding that Body Mass Index (BMI) impacts lifespan through blood pressure, cholesterol levels, and type 2 diabetes. Modifying BMI is key for improving health and extending life.

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Area of Science:

  • Genetics and Epidemiology
  • Longevity Research
  • Metabolic Health

Background:

  • Longevity is influenced by various factors including diet, lifestyle, obesity, and metabolism, but their causal relationships remain unclear.
  • Investigating modifiable risk factors offers potential for interventions to promote healthy aging.

Purpose of the Study:

  • To investigate possible causal relationships between 25 modifiable risk factors and human longevity.
  • To identify key factors that can be targeted to promote longer, healthier lives.

Main Methods:

  • Utilized a random effects model and two-sample Mendelian randomization with genetic variations as instruments.
  • Analyzed data from 11,262 long-lived individuals (≥90 years) and 25,483 controls (≤60 years) from the UK Biobank.
  • Employed Egger regression to assess potential violations of the Mendelian randomization model.

Main Results:

  • Thirteen risk factors showed significant associations with longevity, including smoking initiation, educational attainment, blood pressure, obesity, BMI, and type 2 diabetes.
  • Body Mass Index (BMI) was found to indirectly influence longevity through systolic blood pressure (SBP), plasma lipids (HDL/TC/LDL), and type 2 diabetes (T2D).
  • Consistent associations were observed for smoking initiation, body size at age 10, BMI, obesity, SBP, diastolic blood pressure (DBP), T2D, HDL, LDL, and total cholesterol (TC).

Conclusions:

  • Body Mass Index (BMI) significantly impacts longevity via its effects on SBP, plasma lipids, and T2D.
  • Future health strategies should prioritize BMI modification to enhance overall health and promote longevity.