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Lipidomics profiling of biological aging in American Indians: the Strong Heart Family Study

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Abstract

Telomeres shorten with age and shorter leukocyte telomere length (LTL) has been associated with various age-related diseases. Thus, LTL has been considered a biomarker of biological aging. Dyslipidemia is an established risk factor for most age-related metabolic disorders. However, little is known about the relationship between LTL and dyslipidemia. Lipidomics is a new biochemical technique that can simultaneously identify and quantify hundreds to thousands of small molecular lipid species. In a large population comprising 1843 well-characterized American Indians in the Strong Heart Family Study, we examined the lipidomic profile of biological aging assessed by LTL. Briefly, LTL was quantified by qPCR. Fasting plasma lipids were quantified by untargeted liquid chromatography–mass spectrometry. Lipids associated with LTL were identified by elastic net modeling. Of 1542 molecular lipids identified (518 known, 1024 unknown), 174 lipids (36 knowns) were significantly associated with LTL, independent of chronological age, sex, BMI, hypertension, diabetes status, smoking status, bulk HDL-C, and LDL-C. These findings suggest that altered lipid metabolism is associated with biological aging and provide novel insights that may enhance our understanding of the relationship between dyslipidemia, biological aging, and age-related diseases in American Indians.

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Acknowledgements

We thank all participants of the Strong Heart Study (SHS), the Indian Health Service facilities, and participating tribal communities for their extraordinary cooperation and involvement, which has contributed to the success of SHS.

Funding

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01DK091369 and R01DK107532. Pooja Subedi was partially supported by the American Heart Association predoctoral fellowship 20PRE35050001. The Strong Heart Study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, National Institute of Health, Department of Health and Human Services, under contract numbers 75N92019D00027, 75N92019D00028, 75N92019D00029, and 75N92019D00030. The study was previously supported by research grants: R01HL109315, R01HL109301, R01HL109284, R01HL109282, and R01HL109319 and by cooperative agreements: U01HL41642, U01HL41652, U01HL41654, U01HL65520, and U01HL65521. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Indian Health Service (IHS).

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Author notes

  1. Pooja Subedi and Helena Palma-Gudiel contributed equally to this work.

Authors and Affiliations

  1. Department of Epidemiology, College of Public Health & Health Professions and College of Medicine, University of Florida, 2004 Mowry Road, Gainesville, FL, 32610, USA

    Pooja Subedi, Helena Palma-Gudiel & Jinying Zhao

  2. West Coast Metabolomics Center, University of California-Davis, Davis, CA, USA

    Oliver Fiehn

  3. Missouri Breaks Industries Research Inc, 118 South Willow St., Eagle Butte, SD, 57625, USA

    Lyle G. Best

  4. Center for American Indian Health Research, Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Elisa T. Lee

  5. MedStar Health Research Institute, Hyattsville, MD, USA

    Barbara V. Howard

  6. Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC, USA

    Barbara V. Howard

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  1. Pooja Subedi
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  2. Helena Palma-Gudiel
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  3. Oliver Fiehn
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  4. Lyle G. Best
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  7. Jinying Zhao
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Correspondence to Jinying Zhao.

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All procedures performed in this study were in accordance with the ethical standards of the Indian Health Service Institutional Review Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Subedi, P., Palma-Gudiel, H., Fiehn, O. et al. Lipidomics profiling of biological aging in American Indians: the Strong Heart Family Study. GeroScience 45, 359–369 (2023). https://doi.org/10.1007/s11357-022-00638-9

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