Low-grade chronic inflammation and superoxide anion production by NADPH oxidase are the main determinants of physical frailty in older adults

Abstract

Background. Physical performance measured by gait speed is being recognized as a major instrument for clinical evaluation in older adults, because it predicts physical frailty, loss of autonomy, hospitalization and decreased survival. Low-grade chronic inflammation and oxidative stress, mediated partly by the superoxide anion produced by NADPH oxidase, are closely linked and could be involved in age-related physical decline. Objective. To determine whether slow gait speed is associated with superoxide anion overproduction by NADPH oxidase and low-grade chronic inflammation. Design and setting. Observational study among the 280 elderly of an ambulatory geriatric care unit (191 women, 89 men, 79.9 ± 6.1 years old). Methods. Gait speed was evaluated by walking at self-chosen usual pace. Usual gait speed < 0.8 m/s was defined as slow gait speed. Superoxide anion production was evaluated using a lucigenin-based chemiluminescence method. Inflammation was evaluated by CRP, fibrinogen and leukocyte count. Results. Among the 280 participants, 179 (63.9%) walked with a gait speed < 0.8 m/s (slow walkers) and 101 (36.1%) with a gait speed ≥ 0.8 m/s. Superoxide production and inflammation markers, such as fibrinogen, were more important in slow walkers (p = 0.004 and p = 0.006, respectively). In multivariate analysis, superoxide anion overproduction and fibrinogen were independently associated with physical frailty assessed by slow gait speed (p = 0.028 and p = 0.007, respectively). Conclusion. Physical frailty in older people is associated with superoxide anion overproduction by NADPH oxidase and low-grade chronic inflammation.

Keywords::

• NADPH oxidase
• free radicals
• gait speed
• frailty
• low-grade inflammation
• fibrinogen