# Shared and specific blood biomarkers for multimorbidity

**Authors:** Alice Margherita Ornago, Caterina Gregorio, Federico Triolo, Ann Zenobia Moore, Alessandra Marengoni, Giorgi Beridze, Giulia Grande, Giuseppe Bellelli, Matilda Dale, Claudia Fredolini, Luigi Ferrucci, Laura Fratiglioni, Amaia Calderón-Larrañaga, Davide Liborio Vetrano

PMC · DOI: 10.1038/s41591-025-04038-2 · Nature Medicine · 2026-01-02

## TL;DR

The study identifies blood biomarkers linked to multiple chronic diseases in older adults, suggesting shared biological processes contribute to multimorbidity.

## Contribution

The study identifies shared and specific blood biomarkers associated with multimorbidity and disease accumulation in older adults.

## Key findings

- GDF-15, HbA1c, cystatin C, leptin, and insulin are consistently linked to multimorbidity measures.
- Faster disease accumulation is associated with higher GGT and lower albumin levels.
- Findings were validated in an independent aging cohort with comparable accuracy.

## Abstract

Aging is accompanied by the progressive accumulation of biological deficits, which increases susceptibility to developing multiple chronic diseases (that is, multimorbidity). The biological underpinnings of multimorbidity remain poorly understood. Here we analyzed 54 blood biomarkers reflecting inflammatory, vascular, metabolic and neurodegenerative processes in 2,247 individuals aged 60 and over from the Swedish National Study on Aging and Care in Kungsholmen. Multimorbidity was assessed using three measures: baseline total disease count, baseline multimorbidity patterns identified through latent class analysis and 15-year rate of disease accumulation. Associations between baseline biomarkers and multimorbidity measures were examined using least absolute shrinkage and selection operator regression. Growth differentiation factor 15, hemoglobin A1c, cystatin C, leptin and insulin were consistently and positively associated with all multimorbidity measures. Additional biomarkers demonstrated specific associations with distinct multimorbidity patterns. Moreover, faster disease accumulation was directly associated with gamma-glutamyl transferase and inversely with albumin. Longitudinal results were externally validated in 522 participants from the Baltimore Longitudinal Study of Aging, with comparable predictive accuracy. Our findings suggest that multiple biological processes contribute to multimorbidity through shared and distinct mechanisms. Metabolic disturbances emerged as a key driver of multimorbidity. If confirmed, these processes could represent targets for interventions to mitigate disease accumulation.

Growth differentiation factor 15, hemoglobin A1c, cystatin C, leptin and insulin levels were consistently and positively associated with measures of multimorbidity, both cross-sectional and longitudinal, in individuals aged 60 and over.

## Linked entities

- **Proteins:** GDF15 (growth differentiation factor 15), lepa (leptin a), PIN (insulin precursor), LOC100189571 (uncharacterized LOC100189571), CYSTATIN-C (cystatin-C)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, GDF15 (growth differentiation factor 15) [NCBI Gene 9518] {aka GDF-15, HG, MIC-1, MIC1, NAG-1, PDF}, GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, CST3 (cystatin C) [NCBI Gene 1471] {aka ADLDWA, ARMD11, HEL-S-2}
- **Diseases:** inflammatory (MESH:D007249), Metabolic disturbances (MESH:D024821), multiple chronic diseases (MESH:D002908)

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12920107/full.md

## References

5 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920107/full.md

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Source: https://tomesphere.com/paper/PMC12920107