@article {9483,
	title = {Late-life plasma proteins associated with prevalent and incident frailty: A proteomic analysis.},
	journal = {Aging Cell},
	year = {2023},
	month = {2023 Sep 11},
	abstract = {<p>Proteomic approaches have unique advantages in the identification of biological pathways that influence physical frailty, a multifactorial geriatric syndrome predictive of adverse health outcomes in older adults. To date, proteomic studies of frailty are scarce, and few evaluated prefrailty as a separate state or examined predictors of incident frailty. Using plasma proteins measured by 4955 SOMAmers in the Atherosclerosis Risk in Community study, we identified 134 and 179 proteins cross-sectionally associated with prefrailty and frailty, respectively, after Bonferroni correction (p < 1 {\texttimes} 10 ) among 3838 older adults aged >=65 years, adjusting for demographic and physiologic factors and chronic diseases. Among them, 23 (17\%) and 82 (46\%) were replicated in the Cardiovascular Health Study using the same models (FDR p < 0.05). Notably, higher odds of prefrailty and frailty were observed with higher levels of growth differentiation factor 15 (GDF15; p  = 1 {\texttimes} 10 , p  = 2 {\texttimes} 10 ), transgelin (TAGLN; p  = 2 {\texttimes} 10 , p  = 6 {\texttimes} 10 ), and insulin-like growth factor-binding protein 2 (IGFBP2; p  = 5 {\texttimes} 10 , p  = 1 {\texttimes} 10 ) and with a lower level of growth hormone receptor (GHR, p  = 3 {\texttimes} 10 , p  = 2 {\texttimes} 10 ). Longitudinally, we identified 4 proteins associated with incident frailty (p < 1 {\texttimes} 10 ). Higher levels of triggering receptor expressed on myeloid cells 1 (TREM1), TAGLN, and heart and adipocyte fatty-acid binding proteins predicted incident frailty. Differentially regulated proteins were enriched in pathways and upstream regulators related to lipid metabolism, angiogenesis, inflammation, and cell senescence. Our findings provide a set of plasma proteins and biological mechanisms that were dysregulated in both the prodromal and the clinical stage of frailty, offering new insights into frailty etiology and targets for intervention.</p>},
	issn = {1474-9726},
	doi = {10.1111/acel.13975},
	author = {Liu, Fangyu and Austin, Thomas R and Schrack, Jennifer A and Chen, Jingsha and Walston, Jeremy and Mathias, Rasika A and Grams, Morgan and Odden, Michelle C and Newman, Anne and Psaty, Bruce M and Ramonfaur, Diego and Shah, Amil M and Windham, B Gwen and Coresh, Josef and Walker, Keenan A}
}
