Association of cooking oil and incident of frailty in older adults: a cohort study.

BACKGROUND: Studies examining the potential association between cooking oil and frailty risk in older adults have produced conflicting outcomes. Therefore, our objective was to explore the relationship between cooking oil (vegetable and animal fat oils), changes in oil usage, and the risk of frailty in older adults. METHODS: We included 4,838 participants aged ≥ 65 years without frailty (frailty index < 0.25) from the 2011 wave of the Chinese Longitudinal Healthy Longevity Survey. Follow-up occurred in the 2014 and 2018 waves. Cox proportional hazard models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) to examine the association between cooking oil and frailty. Additionally, we evaluated the effect of switching cooking oil on frailty during the follow-up period. RESULTS: During a median follow-up of 3.0 (2.8-6.9) years, 1,348 individuals (27.9%) developed frailty. Compared to those using vegetable oil, users of animal fat oil had a lower risk of frailty (HR = 0.72, 95% CI: 0.61-0.85). Participants who switched from vegetable oil to animal fat oil, as well as those consistently using animal fat oil, had lower risks of frailty with HRs of 0.70 (0.52-0.95) and 0.63 (0.51-0.77) respectively, compared to those who consistently used vegetable oil. Conversely, individuals who switched from animal fat oil to vegetable oil experienced an increased risk of frailty (HR: 1.41, 95% CI: 1.01-1.97). CONCLUSIONS: The utilization of animal fat oil in cooking exhibited a reduced frailty risk among older adults. Conversely, transitioning from animal fat oil to vegetable oil may elevate the risk. These findings propose that substituting vegetable oil with animal fat oil in the diet may safeguard against frailty.

Wnt5a is associated with the differentiation of bone marrow mesenchymal stem cells in vascular calcification by connecting with different receptors.

Vascular calcification significantly affects the health of the elderly. Increasing evidence proved that vascular calcification is an actively regulated osteogenic process. The osteochondrocytic differentiation of mesenchymal stem cells (MSCs) is a significant step of osteogenic processes. The Wnt pathways has been identified as contributing to the regulation of osteogenic mineralization during development and disease. However, it remains unknown whether these MSCs in the vascular calcification differentiate into normal vascular smooth muscle cells (VSMCs) in vivo in order to treat damaged vascular tissue or into calcified VSMCs to aggravate calcification correlated to the Wnt pathways. Thus, it is necessary to analyze the mechanisms of MSC differentiation in detail. In the present study a cell­cell co­culturing in vitro system was used to observe MSCs that directly interact with normal or calcified VSMCs during calcification and to investigate the gene expression of the Wnt pathways during the process. Direct co­cultures were established by seeding two different cell types, VSMCs or calcified VSMCs, or a mixture of both at ratios of 5,000:5,000 cells/1.7 cm2 onto either gelatin­coated 1.7­cm2 chamber slides for immunohistochemical analysis or gelatin­coated 75­cm2 tissue culture flasks for protein or RNA isolation. Osteoblastic differentiation was evaluated by examining the cell morphology and assessing the activity of alkaline phosphatase in the cell lysates by alkaline phosphatase staining. Additionally, the mRNA expression levels of the genes encoding for proteins involved in the Wnt signaling proteins, Wnt5A, LRP6, Ror2, c­Jun­N­terminal kinase and ß­catenin, were assessed in each group. The present study demonstrated that Wnts are expressed in the progress of differentiation of MSCs during calcification. MSCs can differentiate into different cell phenotypes when there is direct cell­cell contact with VSMCs or calcified VSMCs, and the Wnt5a/Ror2 signaling pathway may be associated with the determination of differentiation of MSCs in this process.

Osteoprotegerin inhibits calcification of vascular smooth muscle cell via down regulation of the Notch1-RBP-Jκ/Msx2 signaling pathway.

OBJECTIVE: Vascular calcification is a common pathobiological process which occurs among the elder population and in patients with diabetes and chronic kidney disease. Osteoprotegerin, a secreted glycoprotein that regulates bone mass, has recently emerged as an important regulator of the development of vascular calcification. However, the mechanism is not fully understood. The purpose of this study is to explore novel signaling mechanisms of osteoprotegerin in the osteoblastic differentiation in rat aortic vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: VSMCs were isolated from thoracic aorta of Sprague Dawley rats. Osteoblastic differentiation of VSMCs was induced by an osteogenic medium. We confirmed by Von Kossa staining and direct cellular calcium measurement that mineralization was significantly increased in VSMCs cultured in osteogenic medium; consistent with an enhanced alkaline phosphatase activity. This osteoblastic differentiation in VSMCs was significantly reduced by the addition of osteoprotegerin in a dose responsive manner. Moreover, we identified, by real-time qPCR and western blotting, that expression of Notch1 and RBP-Jκ were significantly up-regulated in VSMCs cultured in osteogenic medium at both the mRNA and protein levels, these effects were dose-dependently abolished by the treatment of osteoprotegerin. Furthermore, we identified that Msx2, a downstream target of the Notch1/RBP-Jκ signaling, was markedly down-regulated by the treatment of osteoprotegerin. CONCLUSION: Osteoprotegerin inhibits vascular calcification through the down regulation of the Notch1-RBP-Jκ signaling pathway.

The Wnt5a/Ror2 pathway is associated with determination of the differentiation fate of bone marrow mesenchymal stem cells in vascular calcification.

Accumulating evidence have demonstrated that mesenchymal stem cells (MSCs) are involved in the initiation and progression of various vascular diseases. Canonical Wnt signaling controls the fate of MSCs, and plays an important role in vascular calcification. However, vascular calcification can be inhibited by the non-canonical Wnt signaling pathway Wnt5a/Ror2. This study aimed to investigate whether the Wnt5a/Ror2 pathway is associated with determination of the differentiation fate of MSCs in vascular calcification. Direct co-cultures were established by seeding smooth muscle cells (SMCs) or calcified SMCs and MSCs together at ratios of SMCs or calcified SMCs 15x104; SMCs or calcified SMCs 5x104: MSCs 10x104, SMCs or calcified SMCs 10x104: MSCs 5x104. Osteosynthesis-inducing medium (OS) was added to the culture medium in the groups of MSCs with non-calcified SMCs. Cells were cultured for nine days. Osteoblastic differentiation was evaluated by cell morphology and the activity of alkaline phosphatase (ALP) in cell lysates and ALP staining. Furthermore, we investigated the inhibition of Wnt signaling, and observed that the members of the non-canonical signaling pathway Wnt5a/Ror2 were expressed in each group. Additionally, MSCs cultured in culture media with OS did not differentiate into an osteoblast phenotype when in direct contact with non-calcified SMCs, irrespective of the number of MSCs. However, an osteoblast phenotype was observed when MSCs were cultured in media without OS differentiation towards direct contact with calcified SMCs, and the levels of osteoblastic markers had a direct correlation with the number of MSCs. Of note, the Wnt5a protein was associated with the levels of calcification, thus, although rarely detected in non-calcification, Ror2 mRNA in the non-calcified groups was significantly higher compared to that in the calcified groups. Therefore, the Wnt5a/Ror2 pathway is associated with determination of the differentiation fate of bone marrow mesenchymal stem cells in vascular calcification.