Rejuvenation research最新文献

Aging is strongly correlated with several noncommunicable disorders such as diabetes, obesity, cardiovascular disease, and neurodegenerative conditions. Glucosamine (2-amino-2-deoxy-d-glucose, GlcN) is a naturally occurring amino sugar and is reported to act as a caloric restriction mimetic (CRM). In young and d-galactose-induced accelerated rat aging models, we tested a persistent oral dietary dose of GlcN and evaluated various aging biomarkers in erythrocytes and plasma. A significant increase in the reactive oxygen species (ROS) was observed in GlcN-treated young and accelerated senescent rat model. Increased value of ferric reducing ability of plasma (FRAP), superoxide dismutase, catalase, and plasma membrane redox system (PMRS) was observed. We suggest that GlcN induces a mitohormetic impact by a transient increase in ROS. Our findings indicate that GlcN may be a successful CRM.

Theses reviewed in this issue include "Engineering Protein Disaggregases to Counter Alpha-Synuclein and Amyloid-Beta Neurotoxicity," "Hyperglycaemia Induced Immunomodulation of Macrophages in Diabetic Vascular Disease," "Microvasculature-on-a-Chip Systems for Human Disease Modeling," "Senescence Surveillance: The Interplay Between the Immune System and Senescent Cells," "The HMG Transcription Factor TOX Induces a Transcriptional and Epigenetic Program of CD8⁺ T Cell Exhaustion in Chronic Infection and Cancer," and "Zero to One-Translational Advancements in the Field of Xenotransplantation."

d-galactose (d-gal) is widely used to induce aging. However, it is still unclear whether long-term injection of d-gal affects the gastrointestinal functions of aging rats, and how. In this study, we investigated the effects of d-gal on the gastrointestinal functions of aging rats, especially from the perspective of fecal metabolomics. Biochemical and behavioral analyses were performed. Besides, a ¹H NMR-based metabolomics approach was built and applied in combination with multivariate data analysis including principal components analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA). Regarding gastrointestinal functions, d-gal significantly decreased the small intestine propulsion rates and prolonged gastrointestinal transit time. In addition, d-gal significantly increased the oxidative damages. PCA results showed that d-gal interrupted the metabolic profiles of endogenous small molecules in aging rats. Furthermore, OPLS-DA showed that 40 metabolites were screened and identified to be involved in the disruption of gastrointestinal functions in aging rats. Accordingly, seven metabolic pathways were recognized as the most influenced pathways associated with gastrointestinal functions of aging rats induced by d-gal, including amino acid metabolism, energy metabolism, intestinal flora metabolism, and metabolism of short chain fatty acids. It is the first report to investigate the effects and underlying mechanisms of d-gal on gastrointestinal functions of aging rats from the perspective of fecal metabolomics. The current results are conducive to further comprehensively understand d-gal-induced aging and will expand the applications of d-gal in pharmacological researches.

Casein hydrolysate has been shown to improve arterial stiffness as estimated by brachial-ankle pulse wave velocity (baPWV) in untreated hypertensive patients. Facial pigmentation is associated with atherosclerosis, both of which are supposed to be modulated by tissue accumulation of advanced glycation end products (AGEs). However, effects of casein hydrolysate on facial pigmentation and AGEs remain largely unknown. This randomized double-blind placebo-controlled trial evaluated whether and how casein hydrolysate improves facial pigmentation in 80 nonhypertensive Japanese patients. Study participants were randomly assigned to receive either active tablets containing casein hydrolysate or placebo for 48 weeks. Facial pigmentation area, baPWV, and skin accumulation levels of AGEs were evaluated by Robo Skin Analyzer RSA50S II, volume-plethysmographic apparatus, and AGE Reader, respectively, at baseline and at the end of the intervention. Treatment with casein hydrolysate, but not placebo significantly reduced triglycerides and facial pigmentation area. There were significant differences of changes in triglycerides, facial pigmentation area, skin accumulation levels of AGEs, and baPWV between the two groups. Furthermore, changes in triglycerides and skin accumulation levels of AGEs were positively and independently associated with those in facial pigmentation area, whereas changes in baPWV were not. This study suggests that casein hydrolysate reduces facial pigmentation area in nonhypertensive participants partly by decreasing skin accumulation levels of AGEs. Clinical-Trials.gov ID: UMIN000027675.

Theses reviewed in this issue include "An Aging Tug of War: The Accumulation of the Spontaneous L-Isoaspartate Modification in Proteins vs. Canonical and Novel Maintenance Pathways," "Cellular and Molecular Mechanisms Underpinning Microglial Activation During Remyelination," "Early Detection of Cancer Metastasis at a Synthetic Pre-Metastatic Niche Using Inverse Spectroscopic Optical Coherence Tomography," "Magnetic Stem Cell Spheroid Microrobots and Their In Vivo Applications," "Reprogramming Human Endothelium to Hematopoietic Stem Cells with Adaptive Immune Function," and "Scaffold-Free Three-Dimensional Bioprints Repair Small Intestine Injuries and Integrate Into Native Intestine."

To determine the prognostic value of frailty and comorbidity for outdoor mobility loss and mortality in the elderly. The retrospective study was conducted among outpatients aged ≥60 years. Patients with ≥3 chronic illnesses were treated by doctors who had undergone a 72-hour geriatric training. The outdoor low-mobility group comprised patients who failed to visit a doctor because of decreased outdoor mobility during the 3-year follow-up period. The outdoor high-mobility group comprised participants with no outdoor mobility loss. 5678 patients with a mean age of 71.0 ± 0.1 years were included in the study. The risk of outdoor mobility loss rose by 4% per year with men developing it 30% more than women. The effect of frailty was of particular importance because it increased the risk of developing outdoor mobility loss by 70%. Comorbidity was not associated with a higher risk of outdoor mobility loss, but the investigators did not take into account all possible illnesses, or the severity of disease. The loss of outdoor mobility was associated with increase in mortality. Early detection of frailty can help predict outdoor mobility loss and could reduce mortality among older people.

The treatment of hypertrophic scar (HS) has thus far been a clinical challenge. We evaluated the therapeutic effect of CO₂ fractional laser combined with 5-fluorouracil ethosomal gel (5-FU EG) in rabbit HS model. HS model was established as standardized scars on the ventral surface of rabbit ears, divided into four groups: control (no intervention), EG treatment, laser treatment, and combined treatment group (laser plus 5-FU EG). Clinical macroscopic and H&E-stained microscopic observations were conducted to assess HS improvement. The mRNA levels of types I and III collagen, transforming growth factor-β1 (TGF-β1), and interleukin-6 (IL-6) were detected by real-time PCR. After 14 days, H&E staining shows that the thickness of HS in treatment groups was significantly lower compared with the control group, and the thickness in laser treatment group and combined treatment group was significantly lower compared with the EG treatment group. The mRNA levels of types I and III collagen, TGF-β1 were significantly low in all treatment groups, whereas IL-6 was highest in the laser treatment group at day 14. The macro- and microscopic effects of the combined and CO₂ fractional laser treatment were better compared with 5-FU EG only. Inhibition of types I and III collagen, TGF-β1 are the possible underlying mechanism of action, whereas the function of IL-6 remains to be further studied. Our study suggests that the effect of combined 5-FU EG and laser, as well as laser-only treatment are superior to 5-FU EG monotreatment. The mechanism of HS improvement is related to reduction of collagen I/III and the inhibition of TGF-β1 expression.

Electroacupuncture (EA) pretreatment induces cerebral ischemic tolerance; however, the mechanism remains poorly understood. This study aimed to determine the participation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-mediated mitochondrial biogenesis in the neuroprotection of EA and whether cannabinoid receptor 1 (CB1R) is involved in this mechanism. At 2 hours after EA pretreatment, adult male C57BL/6j mice were subjected to 60-minute right middle cerebral artery occlusion (MCAO). Mitochondrial function, the level of mitochondrial biogenesis-related proteins (nuclear transcription factor 1, NRF1; mitochondrial transcription factor A, TFAM), and mitochondrial DNA (mtDNA) were measured. A small interfering RNA (siRNA) targeting PGC-1α and the CB1R antagonists AM251 and SR141716A were given to the animals before EA pretreatment, and mitochondrial function and biogenesis were examined after MCAO. EA ameliorated the mitochondrial function, upregulated the NRF1 and TFAM expression, and increased the mtDNA levels and the volume and number of mitochondria. EA pretreatment increased the expression of PGC-1α, whereas the PGC-1α siRNA and CB1R antagonists reversed the improved neuroprotection and increased mitochondrial biogenesis induced by EA. Our results indicated that EA pretreatment protects the mitochondria and promotes mitochondrial biogenesis by activating CB1R-dependent PGC-1α, which provides a novel mechanism for EA pretreatment-induced ischemic tolerance.

Osteoporosis is a silent disease caused by low bone mineral density and is complicated by fractures. This study was designed to examine the differentiation of uterine stem cell-derived osteoprogenitor cells (UOPCs) both in vitro and in vivo, assessing their effectiveness in treating osteoporosis. CD271⁺/CD45^- UOPCs were isolated from the endometrial tissue of inbred Balb/c mice through magnetic activated cell sorting. Stem cell differentiation assays were used for CD271⁺/CD45^- UOPCs in vitro. In vivo, the UOPCs were implanted into mouse osteoporosis models through tail-vein injection for 8 weeks. Osteogenic differentiation was examined by X-rays and computed tomography (CT) scans. Enhanced green fluorescent protein (EGFP)-labeled UOPCs, obtained from C57BL/6-Tg (ACTb-EGFP) 1Osb/J mice, were used to assess cell survival in the osteoporosis model. The levels of osteogenic markers were assessed by enzyme-linked immunosorbent assay. In vitro, UOPCs were able to form into typical spheres and various differentiations. In vivo, implantation of UOPCs into osteoporosis model significantly increased bone mineral densities and bone microstructure parameters. The levels of a biochemical marker of bone metabolism, Semaphorin-3A, increased significantly. However, levels of receptor activator of nuclear factor kappa-B ligand decreased. Immunofluorescence staining of osteoporosis mice injected with green fluorescent protein+ UOPCs showed their survival for up to 7 days. In conclusion, stem cells with osteogenic differentiation potential can be isolated from uterine or endometrial tissue. These UOPCs can stably proliferate and differentiate in vitro or in vivo, which can inhibit bone resorption and osteoclast marker expression. In vivo, UOPCs significantly improved reduction in bone density caused by reduced estrogen levels. Such cell transplantation approach is potentially useful in the treatment of osteoporosis.