Physiological Role of Serum Growth Differentiation Factor-15 (GDF-15) Level and Iron Metabolism in Community-Dwelling Older Adults.

Background Anemia is common in older adults and, together with heart failure and chronic kidney disease, forms a vicious cycle, whereas diseases such as chronic inflammation and cancer are associated with the anemia of chronic disease (ACD). Researchers have linked growth differentiation factor-15 (GDF-15) to a variety of conditions such as cardiovascular disease, inflammation, cancer, and kidney disease, and have reported hepcidin as a biomarker for iron regulation in ACD. Therefore, anemia, GDF-15, and hepcidin have significance in aging physiology. Hypothesis GDF-15 and hepcidin play important physiological roles in community-dwelling older adults. This study sought to explore the relationship between these biomarkers and anemia, inflammation, or other health outcomes. Methods This was a prospective study of 73 community-dwelling older adults (six men and 67 women, mean age of 76.3 years). Their serum iron level, percentage transferrin saturation (TSAT), high-sensitivity C-reactive protein (hs-CRP), and estimated glomerular filtration rate (eGFR) were measured. Enzyme-linked immunosorbent assays were used to assess their serum GDF-15, ferritin, and hepcidin levels. The participants' grip strength and walking speed were measured. The skeletal muscle mass index (SMI) of each participant was determined by bioelectrical impedance analysis. Results The GDF-15 level was significantly inversely correlated with serum iron, ferritin, and hepcidin levels; percentage TSAT; the eGFR; and gait speed. Serum hepcidin was positively correlated with levels of ferritin, albumin, and hemoglobin. Handgrip strength, SMI, and hs-CRP were not correlated with either GDF-15 or hepcidin levels. After adjusting for age, sex, and body mass index (BMI), multivariate analysis identified the log GDF-15 and serum iron level (log GDF-15: ß=-0.248, iron: ß=0.296) as significant factors determining hemoglobin levels, whose findings have significance due to novel results. Multivariate analysis identified eGFR and levels of hemoglobin and hepcidin as significant factors associated with log GDF-15 (eGFR: ß=-0.406, hemoglobin: ß=-0.269, hepcidin: ß=-0.235). Similarly, ferritin and albumin levels were identified as significant factors associated with hepcidin levels (ferritin: ß=0.590, Alb: ß=0.277). Conclusions Anemia in community-dwelling older adults was determined not only by increasing serum iron levels but also by decreasing GDF-15 levels. Also, the increasing GDF-15 level was determined by a decreasing hepcidin level as well as the presence of anemia and renal dysfunction, and the decreasing hepcidin level was determined by decreasing stored iron and decreasing albumin levels. Serum GDF-15 and hepcidin could potentially inform diagnostic or treatment strategies for anemia or age-related health conditions.

Vascular Endothelial Dysfunction and Autonomic Nervous Hyperactivity among Premenopausal Women with Cold-Sensitivity Constitution (Hiesho).

The cold-sensitivity constitution (CSC), termed "Hiesho" in Japanese, is a woman-specific cold sense of peripheral sites. The etiology of and criteria for CSC are not yet well established. We defined CSC as temperature gradient > 6˚C between body surface and core, and investigated the autonomic nervous activity by measuring heart rate variability and the vascular endothelial function by determining reactive hyperemia index (RHI) in 43 healthy premenopausal women, aged 18-47 years. Twenty five women had CSC during both the follicular and luteal phases of their menstrual cycles (sustained-CSC group), 8 women did not show CSC during both phases (non-CSC group), and the remaining 10 women showed CSC in either menstrual phase (occasional CSC). To identify the pathophysiological bases of CSC, we compared the sympathetic nervous activity and vascular endothelial function between sustained-CSC and non-CSC. We thus found that sympathetic nervous activity was higher among the sustained-CSC group (p = 0.042) during the follicular phase, compared with the non-CSC group, while the RHI was similar in both groups. Furthermore, the sympathetic nervous activity was similar between the sustained-CSC women aged ≥ 40 years (n = 10) and those aged < 40 years (n = 15) during either menstrual phase, whereas the RHI of the women aged < 40 years was lower during the follicular phase (p = 0.045), compared with the women aged ≥ 40 years. In conclusion, CSC is associated with sympathetic nervous hyperactivity in premenopausal women, and vascular endothelial dysfunction is also involved in CSC among younger women.