Low Bone Turnover in Chronic Kidney Disease Is Associated with Decreased VEGF-A Expression and Osteoblast Differentiation

Background: Low turnover bone (low bone formation rates (BFRs)) with decreased osteoblast number is common in patients with chronic kidney disease (CKD) and attributed to ‘over-suppression' of the parathyroid hormone (PTH) despite supra-physiologic levels. An alternative hypothesis is abnormal osteoblast differentiation, resulting in low BFRs due to reduced VEGF-A. Methods: We analyzed the expression of VEGF-A and mesenchymal stem cell (MSC) differentiation factors in freshly isolated bone marrow (BM) cells, and in BM cell-derived MSC in rats with different levels of BFRs and PTH (modulated by calcium and zoledronic acid). The regulators of VEGF in MSC were also determined. Results: VEGF-A expression was reduced in the BM cells from CKD vs. normal animals (p
Source: American Journal of Nephrology - Category: Neurology Source Type: research

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Abstract The p66ShcA protein controls cellular responses to oxidative stress, senescence and apoptosis. Here, we test the hypothesis that aging phenotype(s) commonly associated with broad category of chronic kidney disease are accelerated in diabetic kidneys and linked to the p66ShcA locus. At the organ level, tissue stem cells antagonize senescent phenotypes, by replacing old dysfunctional cells. Using established methods, we isolated a highly purified population of stem cell antigen-1 positive mesenchymal stem cells (Sca-1+ MSCs) from kidneys of Wild Type (WT) and p66 Knock Out (KO) mice. Cells were plated in cu...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Hyperphosphatemia is common in patients with chronic kidney disease and is increasingly associated with poor clinical outcomes. Current management of hyperphosphatemia with dietary restriction and oral phosphate binders often proves inadequate. Tenapanor, a minimally absorbed, small-molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3), acts locally in the gastrointestinal tract to inhibit sodium absorption. Because tenapanor also reduces intestinal phosphate absorption, it may have potential as a therapy for hyperphosphatemia. We investigated the mechanism by which tenapanor reduces gastrointestinal phospha...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
Mesenchymal stromal cell (MSC)-based therapy is a promising strategy for preventing the progression of chronic kidney disease (CKD), with the potential to induce tissue regeneration. In search of the best cell...
Source: Stem Cell Research and Therapy - Category: Stem Cells Authors: Tags: Research Source Type: research
ConclusionsEvaluation of renal anatomy with ultrasound imaging is important at diagnostic workup of FA. While CKD is uncommon at diagnosis, our data suggests that the incidence of CKD increases with age, in particular after haematopoietic stem cell transplantation. Monitoring of renal function is essential for management of FA. Based on these long-term clinical observations, we formulate some practical guidelines for assessment and management of renal abnormalities in FA.
Source: Pediatric Nephrology - Category: Urology & Nephrology Source Type: research
Conclusion: Our study results suggest that MSC-CM can inhibit VSMC calcification. This suggests a potential novel clinical application for MSCs in the treatment of vascular calcification and associated diseases. PMID: 29967775 [PubMed - in process]
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
In conclusion, in the Framingham Heart Study population, in the last 30 years, disease duration in persons with dementia has decreased. However, age-adjusted mortality risk has slightly decreased after 1977-1983. Consequences of such trends on dementia prevalence should be investigated. Recent Research on the Benefits of Exercise in Later Life https://www.fightaging.org/archives/2018/04/recent-research-on-the-benefits-of-exercise-in-later-life/ A sizable body of work points to the ability of older individuals to continue to obtain benefits through regular physical activity, and particularly in the case ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we assessed if activation of the demethylase affects arterial stiffening and hypertension in aged mice. The Klotho gene was originally identified as a putative aging-suppressor gene in mice that extended lifespan when overexpressed and caused multiple premature aging phenotypes when disrupted. The Klotho level decreases with age, while the prevalence of arterial stiffness and hypertension increases with age. At age 70 years, the serum level of Klotho is only about one half of what it was at age 40 years. Moreover, the serum Klotho level is significantly decreased in patients with arterial stiffness in...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Mini-review of kidney disease following hematopoietic stem cell transplant
. Clin Nephrol. 2018 Mar 26;: Authors: Sedhom R, Sedhom D, Jaimes E Abstract Advancements in hematopoietic cell transplantation (HCT) have broadened indications for its use and resulted in more long-term survivors. Stem cell transplantation is associated with several well-known toxicities, although renal complications are not well defined. Acute and chronic kidney disease remains a common complication following transplantation itself. Incidence and risk factors for the development of chronic kidney disease (CKD) is less well ...
Source: Clinical Nephrology - Category: Urology & Nephrology Authors: Tags: Clin Nephrol Source Type: research
In conclusion, senescence of vascular cells promotes the development of age-related disorders, including heart failure, diabetes, and atherosclerotic diseases, while suppression of vascular cell senescence ameliorates phenotypic features of aging in various models. Recent findings have indicated that specific depletion of senescent cells reverses age-related changes. Although the biological networks contributing to maintenance of homeostasis are extremely complex, it seems reasonable to explore senolytic agents that can act on specific cellular components or tissues. Several clinical trials of senolytic agents are currentl...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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