Pro-Inflammatory Proteins Associated with Frailty and Its Progression-A Longitudinal Study in Community-Dwelling Women.

The complex pathophysiology underlying biological aging creates challenges for identifying biomarkers associated with frailty. This longitudinal, nontargeted proteomics study aimed to identify proteins associated with frailty, particularly the change from nonfrail to frail. The population-based Osteoporosis Prospective Risk Assessment cohort includes women all of whom are 75 years old at inclusion (n = 1044) and reassessed at 80 years (n = 715) and 85 years (n = 382). A deficits in health frailty index (FI) and 92 plasma proteins (Olink CVD-II panel) were available at all ages. The identical age facilitated differentiating chronological and biological aging. Bidirectional analyses, performed cross-sectionally and longitudinally, used regression models controlled for false discovery rate (FDR), across 5- and 10-year time windows and longitudinal mixed models. Frailty outcomes were frailty index, frailty status (frail defined as FI ≥ 0.25), change in frailty index, and change in frailty status, together with protein expression or change in protein expression. Elevated levels of 32 proteins were positively associated with the FI, cross-sectionally at all ages (range: ß-coefficients 0.22-2.06; FDR 0.021-0.024), of which 18 were also associated with frailty status (range: odds ratios 1.40-5.77; FDR 0.022-0.016). Based on the accrued data, eight core proteins (CD4, FGF23, Gal-9, PAR-1, REN, TNFRSF10A TNFRSF11A, and TNFRSF10B) are proposed. A one-unit change in the FI was additively associated with increased protein expression over 5 and 10 years (range: ß-coefficients 0.52-1.59; p < 0.001). Increments in baseline FI consistently associated with a change in protein expression over time (5 years, ß-range 0.05-1.35; 10 years, ß-range 0.51-1.48; all p < 0.001). A one-unit increase in protein expression was also associated with an increased probability of being frail (FI ≥ 0.25) (ß-range: 0.14-0.61). Mirroring the multisystem deterioration that typifies frailty, the proteins and their associated biological pathways reflect pathologies, including the renal system, skeletal homeostasis, and TRAIL-activated apoptotic signaling. The core proteins are compelling candidates for understanding the development and progression of frailty with advancing age, including the intrinsic musculoskeletal component. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

A "snap-shot" visual estimation of health and objectively measured frailty: capturing general health in aging older women.

BACKGROUND: In clinic, a subjective visual estimation of a patient's general health often guides interventions, yet little is known of how this assessment relates to objectively measured frailty. AIMS: To characterize the relationship between these two assessments and explore the implication of discordance. METHODS: The study was performed in the OPRA cohort of 75-year old community-dwelling women (n = 1044). Visual perception of health (VPH) was estimated within 15 s from first sight and stratified into tertiles (poor/intermediate/good health). Frailty was measured using a frailty index (FI) (scored 0.0-1.0) and stratified into tertiles: 'frail' (≥ 0.22), 'pre-frail' (0.13-0-21) and 'non-frail' (≤ 0.12). Association between VPH and FI and with 10-year mortality was evaluated using Kaplan Meier curves and Cox proportional hazard models. RESULTS: VPH and FI correlated, but was strongest in those perceived to be in poor health (rs = 0.424, p < 0.001). Approximately half of these women were also objectively frail (53.7%). Similarly, 50.7% perceived to be in good health were also objectively non-frail. However, for one in ten, perceived health was discordant with measured frailty. Subjective and objective measures were associated with mortality, but VPH lacked discrimination in healthier looking women (p = 0.372) compared to FI (p = 0.002). DISCUSSION: Detecting pre-frailty is important to prevent or slow the transition into a frail state. The frailest can be identified with a visual estimation, but only objective frailty assessments can reliably identity pre-frailty. CONCLUSIONS: A visual estimation of health provides valuable complementary information on health, whereas objective assessment of frailty has a broader applicability for health in aging.