生物流体中的GPNMB/骨激活素作为衰老的潜在生物标志物：一项横断面研究。
Biofluid GPNMB/osteoactivin as a potential biomarker of ageing: A cross-sectional study.
作者信息
Liu Yuan-Yuan, Pang Jing, Zhang Chi, Zeng Lv-Tao, Wang Yao, Wang Shi-Bo, Fan Guo-Qing, Zhang Li-Qun, Shen Tao, Li Xue-Fei, Li Chuan-Bao, Cao Su-Yan, Zhang Tie-Mei, Cai Jian-Ping, Cui Ju
机构信息
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing Hospital/National Center of Gerontology of National Health Commission, 1 Dahua Rd, Dongcheng District, Beijing, PR China.
Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China.
出版信息
Heliyon. 2024 Aug 22;10(17):e36574. doi: 10.1016/j.heliyon.2024.e36574. eCollection 2024 Sep 15.
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
In mice, the 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.
背景
糖蛋白非转移性黑色素瘤B（GPNMB）/骨激活素最初是在人黑色素瘤细胞系中被鉴定出来的。GPNMB在抗炎、抗氧化功能以及成骨细胞分化、癌症进展和组织再生中发挥关键作用。最近，GPNMB被用作小鼠的抗衰老疫苗。本研究旨在利用来自中国老年人群的血清和尿液样本，探讨生物体液GPNMB作为人类衰老生物标志物的潜力。
方法
我们分析了来自不同年龄的17个小鼠器官的RNA测序数据（GSE132040），以评估潜在衰老生物标志物的基因表达。采用Spearman相关系数评估基因表达与年龄之间的关系。同时，进行了一项横断面人群研究，该研究包括473名参与者（年龄在25 - 91岁之间），他们是中国彭祖健康老龄化研究（彭祖队列）中有代表性的参与者子集。通过酶联免疫吸附测定（ELISA）测量生物体液GPNMB水平。使用方差分析（ANOVA）、Kruskal - Wallis H检验以及单变量和多变量线性回归分析评估血清和尿液GPNMB水平与各种临床和人体测量指标之间的关联。
结果
在小鼠中，多个器官的mRNA表达水平与年龄呈显著正相关（P < 0.05）。在彭祖队列中，生物体液（血清和尿液）GPNMB水平与年龄呈正相关（P < 0.05）。单变量线性回归分析显示，血清GPNMB水平与骨骼肌质量指数（SMI，P < 0.05）和胰岛素样生长因子1（IGF - 1，P < 0.05）呈负相关，尿液GPNMB水平与总胆汁酸（TBA，P < 0.05）呈负相关。多变量线性回归分析进一步表明，血清GPNMB水平与全身免疫炎症指数（SII，P < 0.05）呈负相关，尿液GPNMB水平与TBA保持负相关（P < 0.05），此外，男性尿液GPNMB水平显著低于女性（P < 0.05）。
结论
生物体液GPNMB是评估生物衰老的强有力的临床生物标志物候选物。
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