Myeloid-derived suppressor cells are increased with age and elevated in donors with a history of cancer; an age-related effect has never been shown in humans. As we age, the composition of our peripheral leukocytes changes dramatically. Many of these alterations contribute to the general immune dysfunction that burdens the elderly, which in turn, contributes to increased susceptibility to disease. MDSCs represent a heterogeneous population of immunosuppressive leukocytes that are elevated in the peripheral blood of cancer patients. Given the relation between cancer incidence and age, this study examined the frequency of peripheral blood CD33(+)HLA-DR(−) MDSCs across three cohorts: healthy adults (19–59 years old), community-dwelling seniors (61–76 years old), and frail elderly (67–99 years old). This analysis is the first to demonstrate that MDSCs and specifically the CD11b(+)CD15(+) MDSC subset are increased with age. Proinflammatory cytokines that are required for the differentiation of MDSCs (e.g., TNF-α, IL-6, and IL-1β) were similarly found to be increased in the serum of the frail elderly. Furthermore, the proportion of MDSCs and the CD11b(+)CD15(+) subset were found to be elevated significantly in elderly donors with a history of cancer. This age-related elevation in the frequency of MDSCs may contribute to the increased cancer incidence that occurs with age. Further investigation into the functional consequences of elevated MDSCs will provide valuable insight into the progression of age-related pathologies.

Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality. We conducted a prospective, observational study of mechanically ventilated critically ill patients with a high incidence of pneumonia in 2 intensive care units (ICUs) in Hamilton, Canada, nested within a randomized trial for the prevention of healthcare-associated infections. The microbial profiles of specimens from 3 anatomical sites (respiratory, and upper and lower gastrointestinal tracts) were characterized using 16S ribosomal RNA gene sequencing. We collected 65 specimens from 34 ICU patients enrolled in the trial (29 endotracheal aspirates, 26 gastric aspirates and 10 stool specimens). Specimens were collected at a median time of 3 days (lower respiratory tract and gastric aspirates; interquartile range [IQR] 2–4) and 6 days (stool; IQR 4.25–6.75) following ICU admission. We observed a loss of biogeographical distinction between the lower respiratory tract and gastrointestinal tract microbiota during critical illness. Moreover, microbial diversity in the respiratory tract was inversely correlated with APACHE II score (r = − 0.46, p = 0.013) and was associated with hospital mortality (Median Shannon index: Discharged alive; 1.964 vs. Deceased; 1.348, p = 0.045). The composition of the host-associated microbial communities is severely perturbed during critical illness. Reduced microbial diversity reflects high illness severity and is associated with mortality. Microbial diversity may be a biomarker of prognostic value in mechanically ventilated patients. ClinicalTrials.gov ID NCT01782755 . Registered February 4 2013.

As humans age, they experience a progressive loss of thymic function and a corresponding shift in the makeup of the circulating CD8+ T cell population from naïve to memory phenotype. These alterations are believed to result in impaired CD8+ T cell responses in older individuals; however, evidence that these global changes impact virus-specific CD8+ T cell immunity in the elderly is lacking. To gain further insight into the functionality of virus-specific CD8+ T cells in older individuals, we interrogated a cohort of individuals who were acutely infected with West Nile virus (WNV) and chronically infected with Epstein Barr virus (EBV) and Cytomegalovirus (CMV). The cohort was stratified into young (60 yrs) groups. In the aged cohort, the CD8+ T cell compartment displayed a marked reduction in the frequency of naïve CD8+ T cells and increased frequencies of CD8+ T cells that expressed CD57 and lacked CD28, as previously described. However, we did not observe an influence of age on either the frequency of virus-specific CD8+ T cells within the circulating pool nor their functionality (based on the production of IFNγ, TNFα, IL2, Granzyme B, Perforin and mobilization of CD107a). We did note that CD8+ T cells specific for WNV, CMV or EBV displayed distinct functional profiles, but these differences were unrelated to age. Collectively, these data fail to support the hypothesis that immunosenescence leads to defective CD8+ T cell immunity and suggest that it should be possible to develop CD8+ T cell vaccines to protect aged individuals from infections with novel emerging viruses. The prevalence and severity of viral infections increases with advanced age, a phenomenon associated with a defective immune system. The thymic output of naïve T cells declines as we age and it is this lack of naïve T cells that is believed to contribute to the inability of the aged to respond to novel infections and develop subsequent memory T cell responses. Here we show that individuals aged 60+ are capable of developing memory CD8+ T cells to West Nile virus, novel pathogen, indistinguishable in terms of polyfunctionality to those of subjects <60 years of age. Furthermore, we show that chronic and life-long infections with CMV and EBV result in similar polyfunctional virus-specific memory CD8+ T cell responses in subjects of all age groups. Our work demonstrates that aged individuals can elicit functional memory CD8+ T cell responses to a new pathogen while maintaining polyfunctional CD8+ T cells against recurrent chronic virus infections. Current vaccine platforms, which rely upon inactivated pathogens or recombinant subunits, are poorly effective in the aged. Our data suggest that live viruses may be more effective vaccine platforms in older humans.

Purpose. The purpose of this review is to investigate the relationship between life-space mobility and cognition in older adults.Methods. MEDLINE, Embase, CINAHL, and PsycINFO were searched through December 2018 for studies containing measures of life-space mobility and cognitive function. Two independent reviewers screened studies. Eligible studies were combined using a random-effects model, and heterogeneity was assessed using theI².Results. Thirty-five articles were identified for review. A moderate and statistically significant association (pooledr = 0.30, 95% confidence interval 0.19 to 0.40.) was observed between life-space mobility and cognition among nine studies. Life-space mobility demonstrated small-to-moderate associations with domain-specific cognitive functioning, particularly executive function, learning, memory, and processing speed. Furthermore, individuals who had restricted life-space mobility (Life-Space Assessment ≤ 40) experienced a steeper decline in cognition (β = 0.56 andp = 0.0471) compared to those who did not (Life-Space Assessment ≥ 41).Conclusion. This review examined the association between life-space mobility and cognitive function in older adults. The results suggest that a moderate relationship between life-space mobility and cognition exists, whether adjusted or unadjusted for covariates such as sociodemographics, mental health, functional capacity, and comorbidities.