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IntroductionFrailty often manifests as an increased vulnerability to adverse outcomes, and detecting frailty is useful for informed healthcare decisions. Veterans are at higher risk for developing frailty and at younger ages. The goal of this study was to investigate approaches in Veterans that can better inform the physiologic underpinnings of frailty, including maximal oxygen uptake (VO2max), 6-min walk, muscle strength, and inflammatory biomarkers.MethodsParticipants (N = 42) were recruited from the Buffalo VA Medical Center. Inclusion criteria: ages 60–85, male or female, any race, and not having significant comorbidities or cognitive impairment. Outcome measures included: the Fried frailty phenotype, the short physical performance battery (SPPB), quality of life (QOL) using the Q-LES-Q-SF, and the following physiologic assessments: VO2max assessment on an upright stationary bicycle, 6-min walk, and arm and leg strength. Additionally, inflammatory biomarkers (C-reactive protein, IL-6, IL-10, interferon-γ, and TNF-α) were measured using ELLA single and multiplex ELISA.ResultsParticipants: 70.3 ± 7.4 years of age: 34 males and 8 females, BMI = 30.7 ± 5.4 kg/m2, 26 white and 16 African American. A total of 18 (42.8%) were non-frail, 20 (47.6%) were pre-frail, and 4 (9.5%) were frail. VO2max negatively correlated with Fried frailty scores (r = −0.40, p = 0.03, N = 30), and positively correlated with SPPB scores (r = 0.50, p = 0.005), and QOL (r = 0.40, p = 0.03). The 6-min walk test also significantly correlated with VO2max (r = 0.57, p = 0.001, N = 42) and SPPB (r = 0.55, p = 0.0006), but did not quite reach a significant association with frailty (r = −0.28, p = 0.07). Arm strength negatively correlated with frailty (r = −0.47, p = 0.02, N = 26), but not other parameters. Inflammatory profiles did not differ between non-frail and pre-frail/frail participants.ConclusionObjectively measured cardiorespiratory fitness was associated with important functional outcomes including physical performance, QOL, and frailty in this group of older Veterans. Furthermore, the 6-min walk test correlated with VO2max and SPPB, but more validation is necessary to confirm sensitivity for frailty. Arm strength may also be an important indicator of frailty, however the relationship to other indicators of physical performance is unclear.

Low 25-OH serum vitamin D (VitD) is pervasive in older adults and linked to functional decline and progression of frailty. We have previously shown that chronic VitD insufficiency in “middle-aged” mice results in impaired anaerobic exercise capacity, decreased lean mass, and increased adiposity. Here, we examine if VitD insufficiency results in similar deficits and greater frailty progression in old-aged (24 to 28 months of age) mice. Similar to what we report in younger mice, older mice exhibit a rapid and sustained response in serum 25-OH VitD levels to differential supplementation, including insufficient (125 IU/kg chow), sufficient (1000 IU/kg chow), and hypersufficient (8000 IU/kg chow) groups. During the 4-month time course, mice were assessed for body composition (DEXA), physical performance, and frailty using a Fried physical phenotype-based assessment tool. The 125 IU mice exhibited worse grip strength (p = 0.002) and inverted grip hang time (p = 0.003) at endpoint and the 8000 IU mice transiently displayed greater rotarod performance after 3 months (p = 0.012), yet other aspects including treadmill performance and gait speed were unaffected. However, 125 and 1000 IU mice exhibited greater frailty compared to baseline (p = 0.001 and p = 0.038, respectively), whereas 8000 IU mice did not (p = 0.341). These data indicate targeting higher serum 25-OH vitamin D levels may attenuate frailty progression during aging.