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Late-life plasma proteins associated with prevalent and incident frailty: A proteomic analysis.
Wednesday,2023-09-13 20:57 America/Los_Angeles — ecterry
| Title | Late-life plasma proteins associated with prevalent and incident frailty: A proteomic analysis. |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Liu, F, Austin, TR, Schrack, JA, Chen, J, Walston, J, Mathias, RA, Grams, M, Odden, MC, Newman, A, Psaty, BM, Ramonfaur, D, Shah, AM, B Windham, G, Coresh, J, Walker, KA |
| Journal | Aging Cell |
| Date Published | 2023 Sep 11 |
| ISSN | 1474-9726 |
| 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 × 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 × 10 , p = 2 × 10 ), transgelin (TAGLN; p = 2 × 10 , p = 6 × 10 ), and insulin-like growth factor-binding protein 2 (IGFBP2; p = 5 × 10 , p = 1 × 10 ) and with a lower level of growth hormone receptor (GHR, p = 3 × 10 , p = 2 × 10 ). Longitudinally, we identified 4 proteins associated with incident frailty (p < 1 × 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> |
| DOI | 10.1111/acel.13975 |
| Alternate Journal | Aging Cell |
| PubMed ID | 37697678 |
| Grant List | U01HL096812 / AG / NIA NIH HHS / United States R01AG023629 / AG / NIA NIH HHS / United States R01HL144483 / HL / NHLBI NIH HHS / United States R01HL134320 / HL / NHLBI NIH HHS / United States U01HL130114 / HL / NHLBI NIH HHS / United States U01HL080295 / HL / NHLBI NIH HHS / United States R01HL132320 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States 75N92022D00005 / HL / NHLBI NIH HHS / United States 75N92022D00004 / HL / NHLBI NIH HHS / United States 75N92022D00003 / HL / NHLBI NIH HHS / United States 75N92022D00002 / HL / NHLBI NIH HHS / United States 75N92022D00001 / HL / NHLBI NIH HHS / United States U01HL096917 / GF / NIH HHS / United States U01HL096902 / GF / NIH HHS / United States U01HL096899 / GF / NIH HHS / United States U01HL096814 / GF / NIH HHS / United States U01HL096812 / GF / NIH HHS / United States |
ePub date:
23/09