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Background Frailty is a complex, multi-dimensional age-related syndrome that increases the susceptibility to adverse health outcomes and poor quality of life. A growing consensus supports the contribution of chronic inflammation and immune system alterations to frailty, however a clear role of such alterations remains to be elucidated. Furthermore, pro- and anti-inflammatory cytokines together with other signaling molecules might spread from activated cells to the adjacent ones through extracellular vesicles (EVs), which have also a role in cellular aging. The aim of the present research was to investigate if EVs play a role in the immune function in frailty. Results In 219 older adults aged 76–78 years, selected from the InveCe.Ab study (Abbiategrasso, Italy), we investigated inflammation and EVs-mediated intercellular communication. C-reactive protein (CRP) and pro- (IL-1β, IL-2, IL-6, IL-8, IL-12 p70, TNFα and IFNγ) and anti- (IL-4, IL-10, IL-13) inflammatory cytokines were evaluated on plasma of Frail and non-Frail subjects. We reported a significant increase in CRP, interleukin-1β and -6 (IL-1β, IL-6) and tumor necrosis factor alpha (TNFα) plasma levels in frailty. In female Fr subjects, we also reported an increase in interferon‐gamma (IFN‐γ) and, surprisingly, in IL-13, an anti-inflammatory cytokine, whose increase seems to oppose the inflammaging theory. An inflammatory panel (toll-like receptors 2 and 4 (TLR2 and TLR4), tumor necrosis factor receptors TNFRec5/CD 40 and TNFRec1B/CD120B) and a panel including receptors involved in cellular senescence (insulin-like growth factor 1 receptor (CD221) and interleukin 6 receptor (IL-6R)) were indeed analysed in plasma isolated large EVs (lEVs) from Frail (n = 20) and non-Frail (n = 20) subjects. In lEVs isolated from plasma of Frail subjects we reported an increase in TLR2 and TLR4, TNFRec5/CD 40 and TNFRec1B/CD120B, suggesting a chronic state of inflammation. In addition, CD221 and IL-6R increases in lEVs of Frail individuals. Conclusions To conclude, the pro-inflammatory status, notably the increase in circulating cytokines is pivotal to understand the potential mechanisms underlying the frailty syndrome. Moreover, cytokines release from EVs, mainly the large ones, into the extracellular space suggest their contribution to the formation of a pro-inflammatory and pro-senescent microenvironment that, in turn, can contribute to frailty.

Longitudinal surveys of older people are very powerful research resources to study social inequalities and monitor older people’s health conditions. However, these surveys pose specific methodological challenges. Response at Wave 1 is a very serious issue; when respondents differ from non-respondents on the variables of interest, research findings may not be accurate. There is currently little knowledge on the processes that drive Wave 1 survey participation in longitudinal surveys of older people. Using a rich set of administrative and survey data from an Italian longitudinal study of older people, we explore the determinants of Wave 1 response and investigate the reasons for refusing to participate. Key findings are that (1) individuals whose partners took part in the survey are nearly four times more likely to participate than those whose partners did not, (2) older men and women show different response patterns, with widowers and women from deprived areas being less likely to respond, (3) the main reason for refusing survey participation is lack of interest in the study.

Receptor for Activated C Kinase 1 (RACK1) pseudosubstrate is a commercially available peptide that directly activates protein kinase C-β (PKCβ). We have recently shown that RACK1 pseudosubstrate, alone or in combination with classical immune activators, results in increased cytokine production and CD86 upregulation in primary leukocytes. Furthermore, we demonstrated a role of PKCβ and RACK1 in chemical allergen-induced CD86 expression and IL-8 production in both THP-1 cells and primary human dendritic cells. Aim of this study was to shed light on the mechanisms underlying RACK1 pseudosubstrate-induced immune activation and to compare it to lipopolysaccharide (LPS). The human promyelocytic cell line THP-1 was used throughout the study. RACK1 pseudosubstrate induced rapid (5 min) and dose-related PKCβ activation as assessed by its membrane translocation. Among the proteins phosphorylated, we identified Hsp27. Both RACK1 pseudosubstrate and LPS induce its phosphorylation and release in culture medium. The release of Hsp27 induced by RACK1 pseudosubstrate was also confirmed in peripheral blood mononuclear cells. To evaluate the role of Hsp27 in RACK1 pseudosubstrate or LPS-induced cell activation, we conducted Hsp27 silencing and neutralization experiments. Both strategies confirmed the central role of Hsp27 in RACK1 pseudosubstrate or LPS-induced cell activation, as assessed by IL-8 production and upregulation of CD86.