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Microbiome-Linked Metabolic Architecture of Accelerated Biological Aging in Humans
Mitsuru Yagi1,2, Ryo Mizukoshi1,2, Keitaro Ito1,2
1Department of Orthopaedic Surgery, School of Medicine, International University of Health and Welfare, Chiba Japan.
Aging and Disease
|April 14, 2026
Summary
Biological aging, linked to frailty and disease, involves specific metabolic and inflammatory markers. This study found elevated biological age in adult spinal deformity patients, associated with methylamine metabolism and inflammation.
Area of Science:
- Gerontology
- Metabolomics
- Inflammation
Background:
- Biological aging is a key factor in frailty and age-related diseases, but its metabolic and inflammatory underpinnings are not fully understood.
- Adult spinal deformity (ASD) is associated with accelerated biological aging.
Purpose of the Study:
- To investigate the metabolic and inflammatory signatures of biological aging in a cohort of patients with ASD.
- To explore the association between biological aging, methylamine metabolism, and inflammation in ASD.
Main Methods:
- An integrated multi-omics approach was used, including plasma metabolomics and targeted proteomics in 120 ASD patients and 480 controls.
- PhenoAge was used to assess biological age, and a trimethylamine N-oxide (TMAO) Pathway Index (TPI) was constructed from methylamine-related metabolites.
Main Results:
- Patients with ASD exhibited significantly higher biological age compared to controls.
- Biological aging in ASD was strongly correlated with methylamine-related metabolites, glycation products, and a composite TPI, independent of age and other factors.
- Tumor necrosis factor-α was selectively associated with biological age and TPI, suggesting a role in the inflammatory component of aging.
Conclusions:
- Methylamine metabolism and chronic inflammation, particularly involving tumor necrosis factor-α, are associated with biological aging in adult spinal deformity.
- These findings provide a hypothesis-generating framework for understanding the metabolic and inflammatory drivers of aging in ASD.
- Higher biological age in ASD correlates with poorer physical function, increased frailty, and reduced quality of life.
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