| Title: | Characterizing aging-related genetic and physiological determinants of spinal curvature |
| Journal: | Communications Medicine |
| Published: | 12 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40652108/ |
| DOI: | https://doi.org/10.1038/s43856-025-01003-5 |
| URL: | https://www.nature.com/articles/s43856-025-01003-5.pdf |
Publication 16984
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Abstract
Background:Increased spinal curvature is one of the most recognizable aging traits in the human population. However, despite high prevalence, the etiology of this condition remains poorly understood.MethodsTo gain better insight into the physiological, biochemical, and genetic risk factors involved, we developed a novel machine learning method to automatically derive thoracic kyphosis and lumbar lordosis angles from dual-energy X-ray absorptiometry (DXA) scans in the UK Biobank Imaging cohort. We carry out genome-wide association and epidemiological association studies to identify genetic and physiological risk factors for both traits.ResultsIn 41,212 participants, we find that on average males and females gain 2.42° in kyphotic and 1.48° in lordotic angle per decade of life. Increased spinal curvature shows a strong association with decreased muscle mass and bone mineral density. Adiposity demonstrates opposing associations, with decreased kyphosis and increased lordosis. Using Mendelian randomization, we show that genes fundamental to the maintenance of musculoskeletal function (COL11A1, PTHLH, ETFA, TWIST1) and cellular homeostasis such as RNA transcription and DNA repair (RAD9A, MMS22L, HIF1A, RAB28) are likely involved in increased spinal curvature.ConclusionsOur findings reveal a complex interplay between genetics, musculoskeletal health, and age-related changes in spinal curvature, suggesting potential drivers of this universal aging trait.</p>
6 Authors
- Frances M. Wang
- J. Graham Ruby
- Anurag Sethi
- Matthew A. Veras
- Natalie Telis
- Eugene Melamud
1 Application
| Application ID | Title |
|---|---|
| 18448 | Investigation of factors contributing to Healthy Aging. |
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