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BRIEF RESEARCH REPORT article

Front. Aging
Sec. Healthy Longevity
Volume 5 - 2024 | doi: 10.3389/fragi.2024.1442017

Is Being Overweight a Causal Factor in Better Survival Among the Oldest Old? A Mendelian Randomization Study

Provisionally accepted
Hongzhe Duan Hongzhe Duan 1*Konstantin G. Arbeev Konstantin G. Arbeev 1Rachel Holmes Rachel Holmes 1Olivia Bagley Olivia Bagley 1Deqing Wu Deqing Wu 1Igor Akushevich Igor Akushevich 1Nicole Schupf Nicole Schupf 2Anatoliy I. Yashin Anatoliy I. Yashin 1Svetlana Ukraintseva Svetlana Ukraintseva 1*
  • 1 Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, United States
  • 2 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, New York, United States

The final, formatted version of the article will be published soon.

    Overweight, defined by a body mass index (BMI) between 25 and 30, has been associated with enhanced survival among older adults in some studies. However, whether being overweight is causally linked to longevity remains unclear. To investigate this, we conducted a Mendelian randomization (MR) study of lifespan 85+ years, using overweight as an exposure variable and data from the Health and Retirement Study and the Long Life Family Study. An essential aspect of MR involves selecting appropriate single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs). This is challenging due to the limited number of SNP candidates within biologically relevant genes that can satisfy all necessary assumptions and criteria. To address this challenge, we employed a novel strategy of creating additional IVs by pairing SNPs between candidate genes. This strategy allowed us to expand the pool of IV candidates with new 'composite' SNPs derived from eight candidate obesity genes. Our study found that being overweight between ages 75 and 85, compared to having a normal weight (BMI 18.5-24.9), significantly contributes to improved survival beyond age 85. Results of this MR study thus support a causal relationship between overweight and longevity in older adults.

    Keywords: Overweight, Longevity, Mendelian randomization, Instrumental variable, Health and Retirement Study, Long Life Family Study, Aging

    Received: 01 Jun 2024; Accepted: 02 Sep 2024.

    Copyright: © 2024 Duan, Arbeev, Holmes, Bagley, Wu, Akushevich, Schupf, Yashin and Ukraintseva. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Hongzhe Duan, Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, United States
    Svetlana Ukraintseva, Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, United States

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