Objectives: To assess the effects of agrimol-containing Agrimonia pilosa Ledeb. extract (APE) for senescent immune cell removal in middle-aged Japanese adults with immunosenescence. Design and Setting: A randomized, double-blind, placebo-controlled, parallel-group study was conducted in Japan between June 2023 and April 2024. Participants: 110 individuals aged 40–59, selected based on CD8+ T cells with highly-expressing-senescence-associated-β-galactosidase (SA-βGal). Intervention: Participants were randomly assigned to receive 50 mg APE containing 0.2 mg of agrimols or a placebo for eight consecutive weeks. Measurements: The primary endpoint was the change in the proportion of CD8+ T cells with high SA-βGal expression at 8 weeks of intake from the baseline. The secondary endpoints included the proportion of CD4+ T cells with high SA-βGal expression, CD4+ and CD8+ T cell subsets, and the ratio of various immune cells. Results: Of the 635 subjects screened, 110 with immunosenescence were included in this study. In total, 55 participants in the placebo group and 53 in the APE group completed the intervention. There were no statistically significant changes in either the primary or secondary endpoints due to APE intake. In the male population, the proportion of CD8+ T cells with high SA-βGal expression was reduced by APE intake (p = 0.044). Furthermore, the proportion of naïve CD8+ T cells increased and the number of effector memory CD8+ T cells decreased with the consumption of APE. Conclusions: APE was suggested to reduce senescent immune cells, indicating its potential as a candidate senolytic agent for humans; however, the results of this study are preliminary data, and further research on APE is needed (clinical trial registration: UMIN000051574).

Systemic inflammation affects psychological processes. Although the association between inflammation and psychophysiological state has been extensively investigated in patients with depression or inflammatory disease, how this relationship manifests in healthy individuals is not clearly known. Not all individuals exhibit distress in response to elevated inflammatory markers, suggesting the presence of psychological moderators. Elucidating the effect of elevated inflammatory markers on healthy adults would broaden the understanding of the relationship between inflammation and psychophysiological state. We investigated the moderating effect of individual factors, including emotion regulation, sleep quality, and interoceptive awareness, on the relationship between inflammatory markers and psychophysiological states in healthy adults. A total of 155 participants aged 30–59 years were assessed for inflammatory markers, individual factors, and subjective psychological and physical symptoms. Hierarchical regression and interaction models revealed that individuals with poor emotion regulation or low-quality sleep showed stronger associations between inflammatory markers and symptoms such as fatigue, somatic complaints, depression, and anxiety. Conversely, individuals with effective emotion regulation or high-quality sleep exhibited attenuated or even reversed associations, suggesting protective effects. Interoceptive awareness showed weaker and more context-dependent moderating effects. These results highlight the importance of psychological traits in modulating the effects of inflammation on mental and physical well-being in clinically healthy adults. Targeted interventions for enhancing emotion regulation and sleep quality may mitigate the psycho-physiological burden of inflammation and reduce the risk of future disease onset. The findings underscore the need for individualized psychoneuroimmunological models that incorporate trait-level moderators to explain variability in stress-related health outcomes.

Recently, senescent T cells in the peripheral blood have been detected using senescence-associated β-galactosidase (SA-βGal) activity and have been used as an endpoint in clinical trials. However, the epidemiological association between the abundance of SA-βGal-stained senescent CD8+ T cells and chronological age has not been fully elucidated. To examine the correlation between the proportion of SA-βGal^high CD8+ T cells and age, we analyzed previously collected clinical trial data. We conducted a cross-sectional analysis of 632 Japanese adults aged 40–59 years who participated in the screening phase of a clinical trial. To characterize senescent CD8+ T cells, we measured the proportion of SA-βGal^high in total CD8+ T cells and each subset—naïve, central memory (TCM), effector memory (TEM), and terminally differentiated effector memory (TEMRA). We then calculated the correlation coefficients between the proportion of SA-βGal^high CD8+ T cells and age. The proportion of SA-βGal^high cells in total CD8+ T cells, naïve, TCM, TEM, and TEMRA CD8+ T cells increased significantly with age. In Japanese adults, the proportion of SA-βGal^high in CD8+ T cells may serve as a useful biomarker of immune senescence.