Centrally Acting ACE Inhibitor Use and Physical Performance in Older Adults.

BACKGROUND: There is conflicting evidence regarding the role of angiotensin-converting enzyme inhibitors and physical function. While some studies show improvements in muscle strength and physical function, others show no significant difference or decreased performance. This ambiguity could be due to differential effects of angiotensin-converting enzyme inhibitor subtypes which can be categorized as centrally or peripherally-acting based upon their ability to cross the blood-brain barrier. OBJECTIVE: The objective of this study is to compare physical performance measures among angiotensin-converting enzyme inhibitor subtype users. METHODS: Design: Cross-sectional Setting: Ambulatory Participants: Performed in 364 participants in the Health and Retirement Study cohort who were ≥ 65 years (median age (IQR) 74.00 (69-80) years. MEASUREMENTS: Average difference in hand grip (kg), gait speed(m/s) and peak expiratory flow (L/min). RESULTS: Compared to participants on a peripherally-acting angiotensin-converting enzyme inhibitor (113 (31%)), those on a centrally-acting agent (251(69%)) had stronger grip strength 28.9 ±1.0 vs 26.3±1.0, p=.011 and higher peak expiratory flow rates 316.8±130.4 vs. 280.0±118.5, p= .011 in unadjusted analysis. After multiple adjustments the difference in PEF remained statistically significant (Estimate(CI) 26.5, 95% CI 2.24, 50.5, p = 0.032). CONCLUSION: Our results suggest that in older adults the use of centrally-acting angiotensin-converting enzyme inhibitors compared to a peripherally acting angiotensin-converting enzyme inhibitors was associated with better lung function in older individuals.

Lactoferrin for the treatment of age-associated inflammation - A pilot study.

BACKGROUND: Chronic inflammation (CI) is a common trait of aging associated with adverse outcomes including mortality. We hypothesized that recombinant human Lactoferrin (rhLf) would reduce chronic inflammation of aging. METHODS: Thirty-six community dwelling older adults were randomly assigned to rhLf or placebo treatment in 1:1 ratio for 3 months. IL-6, sTNFR1, Comprehensive Metabolic Panel (CMP), and Complete Blood Count (CBC) were measured at baseline, 1 month, 3 months, and 6 months. Physical and cognitive measures were completed at same timepoints, including 4-m walking speed (m/s), grip strength (kg), 6-min walking distance (m), home activity measured by accelerometer, trail making test - Part A (s) and - Part B (s), and Digit symbol substitution test (number correctly coded). Primary outcomes were differences in IL-6 and sTNFR1 concentrations evaluated by generalized linear model with log-link and gamma family distribution, controlling for baseline cytokine concentrations. RESULTS: rhLF was well-tolerated. There were a significant number of abdominal complaints and increased drop-out rate in placebo group. Participants in rhLf arm had non-significant lower mean percent increase in IL6 at 3 months (rhLf mean IL-6 6% lower than control, P = 0.843), and sTNFaR1 (rhLf mean 2% lower than control, P = 0.36). No significant changes were observed for the cognitive or physical measures. CONCLUSION: Treatment with rhLf did not significantly alter serum IL6 or sTNFR1 concentrations of older adults. This study may have been underpowered to detect difference, but provided evidence that a larger sample-size could more definitively determine the effect of rhLF on age-associated CI.

Co-Localization of Macrophage Inhibitory Factor and Nix in Skeletal Muscle of the Aged Male Interleukin 10 Null Mouse.

Chronic inflammation is associated with muscle weakness and frailty in older adults. The antagonistic cross-talk between macrophage migration inhibitory factor (Mif), an anti-apoptotic cytokine and NIP3-like protein X (Nix), a pro-apoptotic mitochondrial protein, may play a role in mitochondrial free radical homeostasis and inflammatory myopathies. We examined Nix-Mif interaction in inflammation and aging using young and old, IL-10tm/tm (a rodent model of chronic inflammation) and C57BL/6 mice. In this study, we observed that Nix and Mif were co-localized in skeletal muscles of aged and inflamed mice. We show an inflammation- and age-related association between Nix and Mif gene expression, with the strongest positive correlation observed in old IL-10tm/tm skeletal muscles. The IL-10tm/tm skeletal muscles also had the highest levels of oxidative stress damage. These observations suggest that Nix-Mif cross-talk may play a role in the interface between chronic inflammation and oxidative stress in aging skeletal muscles.