Physical frailty in relation to immunosenescence involving pDC function in the Japanese elderly: a cross-sectional survey study

Physical frailty leads to a decline in both immune function and physical function, which can lead to a worsening of infections in the elderly; however, the mechanisms have not been fully elucidated. This observational study investigated and clarified the relationship between physical frailty and immune function, particularly plasmacytoid dendritic cells (pDCs) function, which plays an important role in infection prevention, in older adults aged 65 years and older. Participants in this study were 141 elderly individuals (mean age 79.5 ± 5.3 years) without chronic diseases who were enrolled in the National Center for Geriatrics and Gerontology - Study of Geriatric Syndromes (NCGG-SGS). We characterized physical frailty according to the J-CHS criteria based on slow walking speed, muscle weakness, fatigue, decreased physical activity, and weight loss. Lymphocyte fractions, prepared from peripheral blood, were used to assess the proportion of cytokine-producing pDC and myeloid dendritic cells (mDCs) upon H1N1 stimulation, and T cell phenotypes. Other analyses included serum cytokine analysis, blood biochemistry, and hematology. The prevalence of physical pre-frailty and frailty was 37% and 9%, respectively. Compared to robust participants, physically frail participants tended to have lower levels of IFN-α + pDC, mDC, and IFN-α + mDC. No particularly significant changes were observed in T cells. Physically frail participants tended to have higher levels of cytokines: IL-1β, IL-10, IL-6, TNF-α, and MIG, compared to robust participants. Logistic regression analysis of IFN-α + pDC showed that physically frail participants had a significantly lower odds ratio for having high levels of IFN-α-producing pDC compared to robust participants. Furthermore, physically pre-frail participants also tended to have a lower odds ratio for having high levels of IFN-α-producing pDC. A broad study of the relationship between the progression to physical frailty and immune indicators in elderly people without chronic diseases suggested that, independent of age and gender, the IFN-α production function of dendritic cells, including pDCs, tends to decline and the inflammatory state tends to increase with the progression to physical frailty. This finding is expected to help understand health vulnerabilities, including reduced resistance to infection, associated with physical frailty and to develop countermeasures.