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The cornea is exposed daily to a number of mechanical stresses including shear stress from tear film and blinking. Over time, these stressors can lead to changes in the extracellular matrix that alter corneal stiffness, cell-substrate structures, and the integrity of cell-cell junctions. We hypothesized that changes in tissue stiffness of the cornea with age may alter calcium signaling between cells after injury, and the downstream effects of this signaling on cellular motility and wound healing. Nanoindentation studies revealed that there were significant differences in the stiffness of the corneal epithelium and stroma between corneas of 9- and 27-week mice. These changes corresponded to differences in the timeline of wound healing and in cell signaling. Corneas from 9-week mice were fully healed within 24 h. However, the wounds on corneas from 27-week mice remained incompletely healed. Furthermore, in the 27-week cohort there was no detectable calcium signaling at the wound in either apical or basal corneal epithelial cells. This is in contrast to the young cohort, where there was elevated basal cell activity relative to background levels. Cell culture experiments were performed to assess the roles of P2Y2, P2X7, and pannexin-1 in cellular motility during wound healing. Inhibition of P2Y2, P2X7, or pannexin-1 all significantly reduce wound closure. However, the inhibitors all have different effects on the trajectories of individual migrating cells. Together, these findings suggest that there are several significant differences in the stiffness and signaling that underlie the decreased wound healing efficacy of the cornea in older mice.

Objectives-To investigate the rates of frailty and frailty characteristics and examine the clinical and neuropsychological correlates of frailty in adults with late life depression (LLD).Methods-Data were used from the evaluation of 134 individuals over the age of 60 years (45 men, 89 women) with a depressive diagnosis who enrolled in studies for the treatment of their depression. Depression, neuropsychological functioning, white matter hyperintensity (WMH) burden via magnetic resonance imaging, and characteristics of frailty were assessed.Results-Fried frailty burden (≥ 3 characteristics) was present in 25% of the sample, with this rate increasing to 45.5% when using clinically meaningful cut-scores for gait speed (< 1 m/s) and physical activity levels (< 1000 kcal/week). Moreover, 62% of the sample exhibited gait slowing (< 1 m/s) or weakness (grip strength), with 29% demonstrating both. Greater frailty burden was associated with greater HRSD severity in covariate adjusted linear regression models (t 127 =2.41, p = .02). Greater frailty burden was not associated with neuropsychological dysfunction, nor was it associated with greater WMH burden.Conclusions-Findings from this study show that frailty, specifically physical frailty deficits in mobility and strength, is highly comorbid in adults with LLD, associated with greater depressive symptom severity, and does not appear to be associated with the vascular depression subtype of LLD. Future research should investigate the relationship between frailty and antidepressant

Objective: Late-life depression (LLD) is a chronic and heterogeneous disorder. Recent studies have implicated non-normative age-related processes in its pathogenesis. This investigation examined both cross-sectional and longitudinal associations between skeletal muscle mitochondrial function and LLD. Methods: Data from 603 men and women from the Baltimore Longitudinal Study on Aging were analyzed, of whom 167 provided data from a follow-up visit. Muscle bioenergetics was measured by postexercise recovery rate of phosphocreatine (PCr) using phosphorus magnetic resonance spectroscopy. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. Results: There was no cross-sectional association between baseline depression status and either the PCr recovery rate constant (kPCr; t= −0.553, df=542; p = 0.580) or mitochondrial capacity largely independent of exercise intensity (adenosine triphosphate maximum [ATP max ]; t = 0.804, df=553; p = 0.422). Covariate-adjusted Firth logistic regression models however showed that greater decreases in skeletal muscle mitochondrial function from baseline to follow-up were associated with higher odds of clinically significant depressive symptoms (CES-D 16) at follow-up (ΔATP max : odds ratio = 2.63, χ 2 = 5.62, df =1; p = 0.018; ΔkPCr: odds ratio = 2.32, χ 2 =5.79, df =1; p = 0.016). Conclusion: Findings suggest that declining skeletal muscle mitochondrial function in older adults is associated with clinically significant depressive symptoms at follow-up, thereby providing preliminary support for the hypothesis that mitochondrial dysfunction may be a

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