Old age-associated enrichment of peripheral T regulatory cells and altered redox status in pulmonary tuberculosis patients.

Aging influences the susceptibility and prognosis to various infectious diseases including tuberculosis (TB). Despite the impairment of T-cell function and immunity in older individuals, the mechanism for the higher incidence of TB in the elderly remains largely unknown. Here, we evaluated the age-associated immune alterations, particularly in effector and Treg responses in pulmonary TB patients. We also evaluated the impact of redox status and its modulation with N-acetyl-cysteine (NAC) in elderly TB. Higher frequency of Treg cells and reduced IFN-γ positive T cells were observed among older TB patients. The elevated number of Treg cells correlated tightly with bacillary load (i.e. disease severity); which declined significantly in response to successful anti-tubercular treatment. We could rescue Myobacterium tuberculosis-specific effector T cell (Th1) responses through various in vitro approaches, for example, Treg cell depletion and co-culture experiments, blocking experiments using antibodies against IL-10, TGF-ß, and programmed death-1 (PD-1) as well as NAC supplementation. We report old age-associated enrichment of Treg cells and suppression of M. tuberculosis-specific effector T (Th1) cell immune responses. Monitoring these immune imbalances in older patients may assist in immune potentiation through selectively targeting Treg cells and/or optimizing redox status by NAC supplementation.

Nordic walking training and nutritional supplementation in pre-frail older Indians: an open-labelled experimental pre-test and post-test pilot study to develop intervention model.

BACKGROUND: Identifying and treating people in a pre-frail state may be an effective way to prevent or delay frailty and preserve their functional capacity. This study aimed to assess the efficacy of, and compliance with, a 12 week individualized nutritional supplementation (INS) and Nordic walking (NW) program in pre-frail older Indians. The primary measure is physical performance, as indicated by Fried's Frailty scale. Other measures include: cognition, as indicated by the Hindi Mental Status Examination; mood, by the Geriatric Depression Scale; and nutritional status, by the Mini Nutritional Assessment. METHODS: This is an open-labeled experimental pre-test and post-test study, which took place from October 2012 to December 2014. The study was approved by Institute Ethics committee (IEC/NP-350/2012/RP-26/2012) at the All India Institute of Medical Sciences (AIIMS), New Delhi. Participants were sixty-six pre-frail elderly, who were randomly allocated into three subgroups, namely: A (NW only), B (INS only), and C (NW and INS). One-way ANOVA was used to statistically assess differences in baseline characteristics for quantitative variables, with the Chi-Square/Fischer exact test utilized for qualitative variables. Paired t-tests were used to assess pre and post intervention difference within the group for quantitative variables, with McNemar's Chi-Square test used for qualitative variables. Kruskal Wallis test was used to assess significant intervention effects among the groups. A p-value < 0.05 was considered as statistically significant. RESULTS: There was significant effect of intervention in gait speed in group A (p = 0.001) and C (p = 0.002), but not in group B (p = 0.926). While there was no significant change in grip strength in Group A (p = 0.488) and B (p = 0.852), a statistically significant increase was observed in group C (p = 0.013). Mood significantly improved in group B (p = 0.025) and C (p = 0.021). No significant difference was noted in cognitive status across groups. Following the interventions, a total of 18.18% of pre-frail participants were classified as non-frail. CONCLUSIONS: Combining NW and INS provides a simple, pragmatic intervention with efficacy in the management of functionally vulnerable older adults, and allows their maintained independence. Future studies should replicate this readily applicable intervention in a larger cohort with a longer follow-up period. TRIAL REGISTRATION: Clinical Trial Registry-India CTRI/2016/05/006937 [Registered on: 16/05/2016]; Trial was Registered Retrospectively.