Research Progress on the Correlation Between Multi-Dimensional Serum Biomarkers and Frailty in the Elderly

DOI: https://doi.org/10.62517/jmhs.202605125

Author(s)

Yaqing Cui1,#, Jiao Zhou1,#, Hua Lin2, Juntao Li1, Zhengyan Shi1, Xuyang Li1, Zhixin Wu1, Jinlei Dong1, Kun Zhu1,*

Affiliation(s)

1Surgical Department, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China 2Nursing Department, Baoji Central Hospital, Baoji, Shaanxi, China #Co-First Author *Corresponding Author

Abstract

With the accelerated aging process in China, frailty has become an important geriatric syndrome that threatens the health of the elderly. Frailty is characterized by decreased physiological reserve and increased physical vulnerability, often leads to adverse health outcomes. Recently, serum factors have received widespread attention as potential biomarkers for early identification and risk assessment of frailty. In terms of chronic inflammation, levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) are significantly elevated in frail individuals, showing a positive correlation with frailty phenotype; homocysteine (Hcy), as a metabolism-related factor, is closely associated with cognitive frailty; 25-hydroxyvitamin D (25(OH)D) and Klotho protein exhibit a protective effect against frailty, and their decreased levels are associated with an increased risk of frailty. Predictive models based on multi-markers have higher diagnostic performance than single markers, and proteomic studies also show the revealed protein signature associated with frailty. However, currently there is a lack of standardized serum factor’s evaluation Protocol. This review provides a scientific basis for early clinical identification and intervention of frailty and the future research directions need focusing on the optimization and application validation of multi-marker combined models.

Keywords

Frailty; Serum Factor; Biomarker; Chronic Disease; Predictive Model

References

[1] Wang Pingping. By 2025, China's Total Population Will Reach 1,404,890,000, with High-quality Development Continuously Advancing. China Information Daily, 2026-01-21(002). DOI: 10.38309/n.cnki.nzgxx.2026.000075 [2] Guo Liangmei, Song Wenjuan, Zeng Qiang. Research progress on frailty assessment and intervention in elderly people. Preventive Medicine, 2025, 37(03): 262-266. DOI: 10.19485/j.cnki.issn2096-5087.2025.03.010 [3] Wang Jin, Wang Lihong, Wang Caixia. Correlation Analysis between Elderly Nutritional Risk Index and Serum Nutritional Indicators in Frail Patients. Chinese Health Care, 2025, (07): 112-114+122 [4] Guo Yiting, Gao Ning, Zhao Mengmiao, et al. Impact of PM2.5 and O3 Exposure on the Occurrence of Frailty in Middle-aged and Elderly Chinese People. China Environmental Science, 1-12 [2026-01-8]. [5] Yu Wenhua, Li Xiaxia, Zhang Wanshu, et al. Quality evaluation of the frailty rapid screening scale. Practical Geriatrics, 2025, 39(10): 1009-1013 [6] Cheng Wei, Ma Juan, Zhang Ziyan, et al. Research progress of gait perception technology in frailty assessment of the elderly. Geriatrics and Health Care, 2025, 31(06): 1579-1582 [7] Wang Xiaofeng. Research progress on biomarkers of frailty. Geriatrics and Health Care, 2024, 30(05): 1208-1212 [8] Chen Yuliang. Study on the correlation between serum procalcitonin (PCT) and interleukin-6 (IL-6) levels and elderly frailty. Journal of Aerospace Medicine, 2019, (02): 129-132 [9] Zhang Miaoyu, Luo Kexue, Gao Yanfei, Li Hongchun, Zhong Lingling. Correlation analysis between serological indicators and frailty degree in elderly inpatients. Chinese Journal of General Practice, 2021, (03): 358-361 [10] He L, Yang J, Fang Y. Longitudinal analysis on inflammatory markers and frailty progression: based on the English longitudinal study of aging. Eur Geriatr Med, 2024, 15(5): 1323-1330 [11] Kang M G, Jung H W, Kim B J.A link between systemic low-grade inflammation and frailty in older adults: clinical evidence from a nationwide population-based study. Korean J Intern Med, 2024, 39 (6): 1011-1020. [12] Zhang Jia, Cheng Xiujun, Tian Peili, et al. The Value of BPV Combined with Serum Hcy Detection in Assessing Cognitive Function in Elderly Patients with Frail Hypertension. Journal of Bengbu Medical University, 2025, 50(10): 1357-1362 [13] Alvarez-sanchez N, Alvarez-rios Al, Guerrero JM, et al. Homocysteine and C Reactive protein levels are associated with frailty in older Spaniards: the Toledo study for healthy aging. Gerontol A Biol Sci Med Sci, 2020, 75(8): 1488-1494 [14] Dai Jingrong, Li Yan, Li Jie, Huang Hong, He Xu, Xiao Fei, Huang Fang, Liu Qingfang. Study on the correlation between serum homocysteine, 25-hydroxyvitamin D, frailty, and sarcopenia in elderly patients with type 2 diabetes mellitus. Chinese Journal of Diabetes, 2025, (11): 820-826 [15] Stacy A. Castner, Shweta Gupta, et al. Longevity factor klotho enhances cognition in aged nonhuman primates. Nature Aging. 2023, (3): 931-937 [16] AN C, CHEN X, ZHENG D. Association between anemia and serum Klotho in middle-aged and older adults. BMC Nephrol, 2023, 24(1): 38-48. [17] Qin Li, Ge Libin, Liang Zhenzhen, Chen Liang, Chen Chuan. Study on the correlation between frailty and serum factors in elderly community residents. Chinese Journal of General Practice, 2021, (12): 2072-2076 [18] Fritzenschaft L, Boehm F, Rothenbacher D, Denkinger M, Dallmeier D. Association of blood biomarkers with frailty-A mapping review. Ageing Res Rev. 2025 Jul; 109: 102761. doi: 10.1016/j.arr. 2025.102761. Epub 2025 May 1. PMID: 40318768 [19] Sanish Sathyan, Tina Gao, rica F, Weiss,et al. A Frailty-Based Plasma Proteomic Signature Capturing Overall Health and Well-Being in Older Adults. Aging Cell, 2025; 0: e70144 [20] Yiming Pan, Lina Ma. Inflammatory markers and physical frailty: towards clinical application. Immunity & Ageing. (2024) 21: 4.