Decreased cobalamin sensitivity and biological aging acceleration in the general population

Fan Tang; Hongbin Qiu; Yan Liu; Junchen Guo; Zheming Huang; Shaohong Fang; Yiying Zhang; Shanjie Wang

doi:10.1016/j.jnha.2024.100262

Decreased cobalamin sensitivity and biological aging acceleration in the general population

J Nutr Health Aging. 2024 May 20;28(7):100262. doi: 10.1016/j.jnha.2024.100262. Online ahead of print.

Authors

Fan Tang¹, Hongbin Qiu², Yan Liu², Junchen Guo³, Zheming Huang², Shaohong Fang³, Yiying Zhang⁴, Shanjie Wang⁵

Affiliations

¹ Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China; Department of Epidemiology and Biostatistics, School of Public Health, Jiamusi University, Jiamusi, China.
² Department of Epidemiology and Biostatistics, School of Public Health, Jiamusi University, Jiamusi, China.
³ Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China.
⁴ Department of Epidemiology and Biostatistics, School of Public Health, Jiamusi University, Jiamusi, China. Electronic address: zhangyiying@jmsu.edu.cn.
⁵ Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin, China. Electronic address: shanjie_wang@hrbmu.edu.cn.

PMID: 38772151
DOI: 10.1016/j.jnha.2024.100262

Abstract

Background: The evidence on the association between cobalamin (Cbl) and aging or relevant outcomes is limited and controversial. We aimed to investigate the relationships between cobalamin intake- and function-related biomarkers and biological aging.

Methods: The study encompassed 22,812 participants aged 20 years and older from the National Health and Nutrition Examination Survey. A panel of biomarkers or algorithms was used to assess biological aging, including Klemera-Doubal Age Acceleration (KDMAccel), Phenotypic age acceleration (PhenoAgeAccel), telomere length, α-Klotho, and PhenoAge advancement. Weighted generalized linear regression analysis was used to assess the associations between cobalamin-intake biomarkers (serum cobalamin, cobalamin intake from food, cobalamin supplement use, serum methylmalonic acid [MMA], and homocysteine [Hcy]) and function-related biomarkers (functional cobalamin deficiency and cobalamin insensitivity index).

Results: Among the 22,812 individuals, the weighted mean (SE) age was 48.3 (0.2) years and 48.0% were males. Unexpectedly, serum and dietary cobalamin as well as serum MMA and Hcy levels were positively associated with most indicators of biological aging. Cobalamin sensitivity was assessed by the combination of binary Cbl_low/high and MMA_low/high or Hcy_low/high (cutoff values: 400 pg/mL for cobalamin, 250 nmol/L for MMA, and 12.1 μmol/l for Hcy) and a newly constructed cobalamin insensitivity index (based on the multiplicative term of serum cobalamin and serum MMA or Hcy). The multivariable-adjusted β (95%CIs) of KDMAccel in the MMA_lowCbl_low, MMA_lowCbl_high, MMA_highCbl_low, and MMA_highCbl_high groups were reference, 0.27 (0.03 to 0.51), 0.85 (0.41 to 1.29), and 7.97 years (5.77 to 10.17) respectively, which were consistent for the combination of serum Hcy and cobalamin. Both cobalamin insensitivity indices were robustly associated with biological aging acceleration in a dose-response pattern (each p < 0.001).

Conclusions: Decreased cobalamin sensitivity but not cobalamin insufficiency might be associated with biological aging acceleration. Further studies would improve understanding of the underlying mechanisms between decreased cobalamin sensitivity and biological aging acceleration.

Keywords: Biological aging; Cobalamin; Homocysteine; KDM age; Methylmalonic acid; Phenotypic age.