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Aging Cell

Immune cells may link aging and osteoporosis in humans

An observational analysis of 278,164 UK Biobank participants and analyses of human genetic data linked aging and osteoporosis-related traits in both directions.

Paper by Xin Li, Meng-Yuan Yang, Si-Rui Gai, +13 more authorsHou-Feng Zheng · Suzhou Laboratory of Precision Health and Data Science The Second Affiliated Hospital of Soochow University Suzhou Jiangsu China
Graphical abstract from Aging Cell
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Graphical abstract. Li et al., CC BY

Our read

Mechanisms
Studied:
Computational study of human participants and bone marrow cells (Independent replication)
What changed:
Macrophages were linked to both aging and bone density; human validation linked macrophages most strongly to aging
The catch:
Macrophage associations relied on cell-population averages rather than individual-cell gene expression
Why it’s aging research:
It looks at how biology varies with age or lifespan.

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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Among 278,164 UK Biobank participants, an observational analysis linked older age to lower heel bone density. People with lower density or a fracture history had lower survival rates. The work investigated osteoporosis, a condition that weakens bones.

A Mendelian randomization analysis, which uses genetic variants, linked aging measures and osteoporosis-related traits in both directions. Combining human genetic data with gene activity measured in individual mouse cells pointed to macrophages, a type of immune cell, as possible links. A separate analysis of human bone marrow data associated macrophages most strongly with an aging measure. In two mouse bone marrow datasets, the share of macrophages decreased with age. The authors proposed that these cells help connect aging and osteoporosis.

Why it matters

Osteoporosis is an age-related disorder. The proposed role for immune cells offers a focus for investigating how bone loss connects with the wider aging process.

Caveats

The proposed cell mechanism came from genetic and gene-activity associations, not experiments testing whether changing macrophages alters bone loss. The age-related decrease in their share was measured in mouse bone marrow, not people.

Where the evidence stands

TGFB1

Cells: replicated by independent labs. Mice and humans: a single group. Worms or flies: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

No results posted: trials that ended over a year ago with no results on ClinicalTrials.gov and no paper reporting them.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 57 independent labs in 22 countries
  • 1 finding against
  • 2 trials, 1 with no results posted
  • Funders: National Natural Science Foundation of China and others
  • 7 of 71 findings with company ties
  • 2 of 2 trials sponsored by developers of drugs aimed at it

From the paper

Result

Specifically, using IVW estimates as the primary metric, higher genetically determined GrimAge (aging) was associated with lower eBMD (OR = 0.96, 95% CI = 0.95–0.97) and higher fracture risk (OR = 1.03, 95% CI = 1.01–1.05).

Results, 3.1 A Bilateral Relationship Between Aging and BMD/Fracture

Limitation

First, integrating GWAS summary statistics with single-cell sequencing data using methods such as sc-eQTL analysis would strengthen the validity of our observations.

4 Discussion

Quoted word for word from the full text on onlinelibrary.wiley.com.

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