Decreased serum level of HMGB1 and MyD88 during human aging progress in healthy individuals.

AIMS: Previous studies have suggested that high mobility group box-1 protein (HMGB1) binds to the toll-like receptor 4 (TLR4) signaling mediates the progression of various inflammatory diseases. But the roles of HMGB1 and TLR4 in aging remain poorly unknown. In this study, we aimed to investigate the serum levels of HMGB1 and myeloid differentiation factor 88 (MyD88), which is one of TLR4's intracellular adaptor proteins during human aging process and their relevance with cathepsin B (CTSB). METHODS: This research was conducted using the blood samples provided by healthy people (n = 90, 63 men and 27 women). Subjects were subdivided into groups with respect to age: young (about 25 years old, n = 30), middle age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of HMGB1, MyD88 and CTSB were measured using an enzyme-linked immunosorbent assay. RESULTS: The serum levels of HMGB1 and MyD88 were significantly decreased in the aged group compared with those in the young group. Linear regression analysis showed that HMGB1 and MyD88 positively correlated with CTSB among the whole healthy people. A negative correlation was determined between MyD88 and age. CONCLUSIONS: The serum levels of HMGB1 and MyD88 significantly decreased with age. MyD88, but not HMGB1, was negatively correlated with age.

Serum levels of cathepsin D, sirtuin1, and endothelial nitric oxide synthase are correlatively reduced in elderly healthy people.

AIM: Nowadays, cathepsins have been reported to be related to aging. The aim of this study is to evaluate the association between serum levels of cathepsin D (CTSD) and human aging. METHODS: In the present study, we analyzed the serum levels of CTSD and its relation with levels of sirtuin1 (SIRT1) and endothelial nitric oxide synthase (eNOS) activity, which were known having an important role in aging. This study recruited 90 healthy subjects (62 men and 28 women), which were subdivided into three groups with respect to age: young (about 19 years old, n = 30), middle-age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of CTSD and SIRT1 were measured by enzyme-linked immunosorbent assay, and eNOS activity was assessed by the conversion of 14(C)-L-arginine to 14(C)-L-citrulline. RESULTS: Elderly subjects had significantly lower CTSD, SIRT1, and eNOS than younger ones. Serum levels of CTSD were negatively correlated with age. There was a statistically significant positive correlation between serum levels of CTSD, eNOS, and SIRT1. CONCLUSIONS: This study shows lower serum CTSD values in elderly subjects than in younger subjects. This is the first to demonstrate age-related changes in cathepsin D levels in humans and the association between SIRT1 and eNOS.

Differential levels of cathepsin B and L in serum between young and aged healthy people and their association with matrix metalloproteinase 2.

OBJECTIVE: Most publications describe cathepsin B and L as tumor and metastasis factors. These proteases also play a very important role in aging process. The aim of this study was to evaluate the serum level of cathepsin B and L with aging and their association with matrix metalloproteinase 2 (MMP2), which was reported to associate with age-related diseases. METHODS: This research was conducted using blood samples provided by healthy people (n=90, 63 men and 27 women). Subjects were subdivided into groups with respect to age: young (about 18-30 years old, n=30), middle age (about 36-50 years old, n=30), and aged (above 56 years old, n=30). Altered serum level of cathepsin B, cathepsin L, and MMP2 with aging was studied by enzyme-linked immunosorbent assay (ELISA) and Western blotting using discriminative antibodies specific for each factor. RESULTS: ELISA and Western blotting revealed that the serum level of cathepsin L and MMP2, but not cathepsin B significantly decreased in aged group compared with young group. Cathepsin L positively correlates with MMP2 among the whole healthy people (r(2)=0.869, p<0.0001). CONCLUSION: The serum level of cathepsin L decreased with age, while cathepsin B remained no significant difference between young and aged individuals. In addition, cathepsin L positively correlates with MMP2. PRACTICE: The cathepsin L may be used as a monitoring index in age-related diseases. IMPLICATIONS: In addition to cathepsin B, cathepsin L may be also involved in the aging process.