Osteoblast apoptosis plays an important role in age-related bone loss and osteoporosis. Our previous study revealed that advanced oxidation protein products (AOPPs) could induce nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) production, cause mitochondrial membrane potential (ΔΨm) depolarization, trigger the mitochondria-dependent intrinsic apoptosis pathway, and lead to osteoblast apoptosis and ultimately osteopenia and bone microstructural destruction. In this study, we found that AOPPs also induced mitochondrial ROS (mtROS) generation in osteoblastic MC3T3-E1 cells, which was closely related to NOX-derived ROS, and aggravated the oxidative stress condition, thereby further promoting apoptosis. Removing excessive ROS and damaged mitochondria is the key factor in reversing AOPP-induced apoptosis. Here, by in vitro studies, we showed that rapamycin further activated PINK1/Parkin-mediated mitophagy in AOPP-stimulated MC3T3-E1 cells and significantly alleviated AOPP-induced cell apoptosis by eliminating ROS and damaged mitochondria. Our in vivo studies revealed that PINK1/Parkin-mediated mitophagy could decrease the plasma AOPP concentration and inhibit AOPP-induced osteoblast apoptosis, thus ameliorating AOPP accumulation-related bone loss, bone microstructural destruction and bone mineral density (BMD) loss. Together, our study indicated that therapeutic strategies aimed at upregulating osteoblast mitophagy and preserving mitochondrial function might have potential for treating age-related osteoporosis.

Myeloid-derived suppressor cells (MDSCs) are recognized as a key mediator of immunosuppression in aging, which induce immunosenescence and increase elderly people’s susceptibility to infections, cancers, autoimmune diseases, and degenerative diseases. However, the commonly used MDSC markers overlap with those defining healthy and normal neutrophils or monocytes, which makes it challenging to distinguish MDSCs from their myeloid counterparts, and hampers deeper understanding of the pathophysiological functions of MDSCs. In this study, we compared MDSCs from aged mice to young controls using single-cell RNA sequencing. We established MDSC-specific gene signature, which revealed the general characteristics of MDSCs during aging, and thus facilitating distinguishing them from normal myeloid cells. Experimental study revealed that CD300c may serve as a specific marker for improved detection and enrichment of MDSCs in aging. CD11b ⁺ Gr1 ⁺ CD300c ⁺ cells demonstrated a robust ability of T cell suppression. The universality and applicability of MDSC-specific gene signature have also been demonstrated in human myeloid cells. We also found that MDSCs from aged individuals shared the similar developmental trajectory with their myeloid counterparts, and may develop from mature myeloid cells, both in mice and human beings, which has been reported by a limited number of studies. Overall, our work extends the understanding of MDSCs in aging process.

Background: This study was conducted to compare differences in imaging features and clinical symptoms between patients with single-level isthmic spondylolisthesis (IS) at L4 and at L5 and to investigate the correlation between imaging and clinical parameters. Methods: This cross-sectional study evaluated patients with single-level IS who were enrolled between June 2011 and June 2018. A total of 139 patients, 44 in the L4 IS group and 95 in the L5 IS group, met the study criteria and were included. Imaging and clinical parameters obtained from the two groups were compared and analyzed. Results: Patients in the L4 IS group had smaller lower lumbar lordosis (LLL) (27.1 ± 8.2 vs. 30.9 ± 9.3, P = 0.021) and were of older age (58.5 ± 8.7 vs. 52.8 ± 10.1, P < 0.01) than those in the L5 IS group. As per the Roussouly classification system, most patients with L4 IS were classified as Type 2 (43.2%), whereas most patients with L5 IS fell under Type 3 (44.2%). In the L5 IS group, pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), and L5 incidence (L5I) were positively associated with slippage rate (SR), but the lumbosacral angle (LSA) was negatively associated with SR (P < 0.01). In the L4 IS group, only L5I showed a positive association with SR (P < 0.01). More significant associations were found among sagittal lumbo-pelvic parameters in the L5 IS group, but none were found between SR and Oswestry Disability Index (ODI) in either group. Conclusions: When compared with patients with L5 IS, patients with L4 IS were of older age and had straighter low lumbar curvature when they were obviously symptomatic. PI was an important parameter for patients with L5 IS while for those with L4 IS, L5I deserved more attention for its significantly positive correlation with the degree of slippage.