Biofluid GPNMB/osteoactivin as a potential biomarker of ageing: A cross-sectional study
Open accessAbstract
Background: Glycoprotein non-metastatic melanoma B (GPNMB)/osteoactivin was first identified in the human melanoma cell lines. GPNMB plays a key role in the anti-inflammatory and antioxidative functions as well as osteoblast differentiation, cancer progression, and tissue regeneration. Recently, GPNMB was used as an anti-aging vaccine for mice. The present study aimed to investigate the potential of biofluid GPNMB as an aging biomarker in humans using serum and urine samples from an aging Chinese population. Methods: We analyzed RNA-sequencing data (GSE132040) from 17 murine organs across different ages to assess the gene expression of potential ageing biomarkers. Spearman's correlation coefficients were used to evaluate the relationship between gene expression and age. Meanwhile, a cross-sectional population study was conducted, which included 473 participants (aged 25-91 years), a representative subset of participants from the Peng Zu Study on Healthy Ageing in China (Peng Zu Cohort). Biofluid GPNMB levels were measured by ELISA. The associations of serum and urine GPNMB levels with various clinical and anthropometrical indices were assessed using ANOVA, Kruskal-Wallis H test, and univariate and multivariate linear regression analyses. Results: mRNA expression levels showed a significant positive association with age in multiple organs in mice (P < 0.05). In Peng Zu Cohort, biofluid (both serum and urine) GPNMB levels showed a positive correlation with age (P < 0.05). Univariate linear regression analysis revealed that serum GPNMB levels were negatively associated with skeletal muscle mass index (SMI, P < 0.05) and insulin-like growth factor 1 (IGF-1, P < 0.05), and urine GPNMB levels showed a negative association with total bile acids (TBA, P < 0.05). Multivariate linear regression analysis further indicated that serum GPNMB levels negatively correlated with the systemic immune-inflammation index (SII, P < 0.05), and the urine GPNMB levels maintained a negative association with TBA (P < 0.05), additionally, urine GPNMB levels in men were significantly lower than in women (P < 0.05). Conclusions: The biofluid GPNMB was a strong clinical biomarker candidate for estimating biological aging.
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Other urinary protein biomarkers (α-klotho and osteoactivin (GPNMB)) have previously demonstrated utility as predictive markers of biological age and senescent cell load, and have been altered by senolytic intervention in previous preclinical and clinical populations.
“Further, there are other urinary protein biomarkers (i.e. α-klotho and osteoactivin (GPNMB)) that may have great value in future clinical senolytic trials, which have previously demonstrated utility as predictive markers of biological age [72] and senescent cell load [73]. Both have successfully been altered by senolytic intervention in previous preclinical and clinical populations [73,74].”
From Evaluation of exploratory fluid biomarkers from a phase 1 senolytic trial in mild Alzheimer's disease (2025) · cites this paper as [72]
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- Authors
- Liu, Y.-Y., Pang, J., Zhang, C., Zeng, L.-T., Wang, Y., Wang, S.-B., Fan, G.-Q., Zhang, L.-Q., Shen, T., Li, X.-F., Li, C.-B., Cao, S.-Y., Zhang, T.-M., Cai, J.-P., & Cui, J.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Cui, Ju
- Venue
- Heliyon
- Publisher
- Elsevier BV
- Published
- 2024-09
- Volume
- 10
- Issue
- 17
- Pages
- e36574
- ISSN
- 2405-8440 (ISSN-L)
- PMC
- PMC11388787
- OpenAlex
- W4401821816
- Cited by
- 6
- References
- 67
- Citations by year
- 2026: 2 · 2025: 4
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Heliyon (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (2018YFC2000300, 2020YFC2002700, 81970745, 81770228, 82073264)
- National Key Research and Development Program of China (2020YFC2002700, 2018YFC2000300)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
- Keywords
- GPNMB, biological aging, aging biomarkers, serum biomarkers, urinary biomarkers, skeletal muscle index, insulin-like growth factor I, total bile acids, systemic immune-inflammation index, sex differences, healthy aging
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