Curcumin Affects Adipose Tissue-Derived Mesenchymal Stem Cell Aging Through TERT Gene Expression

Abstract

Aging and losing cell survival is one of the main problems in cell therapy. Aging of Mesenchymal Stem Cells (MSCs) is associated with a rise in intracellular reactive oxygen species, decrease in telomerase reverse transcriptase (TERT) expression and finally eroded telomere ends. Given that the production of free radicals in the aging process is effective, the use of antioxidants can help in scavenging free radicals and prevent the aging of cells. The aim of this study is to evaluate the effects of curcumin on proliferation, aging and TERT expression of rat adipose tissue-derived stem cells (rADSC). rADSCs were isolated from inguinal rat adipose tissue and their viabilities were assessed by MTT after exposure to different concentrations of curcumin. Flow-cytometry was performed for investigating the cell surface markers. Adipogenic and osteogenic differentiation were carried out to evaluate the pluripotency of rADSCs. Telomerase expression and percentage of senescent cells were evaluated using real-time PCR and senescence-associated β-galactosidase activity, respectively. The results demonstrated significant proliferation of rADSCs after 48 h treatment with 1 and 5 µM curcumin. Additionally, these concentrations could significantly reduce the population doubling time and aging of rADSCs at different passages. The findings of SA-ß-gal staining showed that curcumin significantly decreased the number of senescent cells in the 5 and 7 cell passages. Moreover, expression levels of TERT increased in the presence of 1 and 5 µM curcumin than control group (P<0.001). As a conclusion, curcumin may be a good candidate to improve lifespan of rADSCs through promoting TERT gene expression.

Histone Deacetylase Inhibitor (Trapoxin A) Enhances Stemness Properties in Adipose Tissue Derived Mesenchymal Stem Cells

“…The mechanisms of functional decline of ASCs at expansion conditions are not clear. The study by Li et al, revealed that MSCs changes are in both gene expression and epigenetic levels represented with reduced expression of stemness genes including Oct-4 and Sox2, along with dysregulations of histone acetylation [8], reduced proliferation potential, some phenotypic changes, tendency for spontaneous differentiation, and aging [9]. Since genetic manipulations of stem cells is not always possible and may raise some risks for clinical applications, using the epigenetic mechanisms for maintaining self-renewal and stemness properties is ideal.…”

The anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats

“…ACR intoxication signi cantly reduced the expression of TERT in the brain, suggesting the TERT-related anti-apoptotic function participated in the ACR neurotoxicity [5]. Interestingly, some new evidences showing that curcumin up-regulates function of TERT have emerged [27,28]. Curcumin extracted with ethyl acetate concentration-dependently upregulated the TERT mRNA expression in rat clone-9 hepatocytes [27].…”

“…Curcumin extracted with ethyl acetate concentration-dependently upregulated the TERT mRNA expression in rat clone-9 hepatocytes [27]. Pirmoradi et al [28] reported that the TERT expression of rat adipose tissue-derived stem cells was signi cantly increased in the presence of curcumin at concentrations of 1 and 5 µM. In line with these in vitro studies [27,28], we showed the curcumin-induced in vivo up-regulation of TERT at the levels of gene and protein, which might be one mechanism underlying the anti-apoptotic activity of curcumin in ACR-intoxicated brains.…”

New Insights for Cellular and Molecular Mechanisms of Aging and Aging-Related Diseases: Herbal Medicine as Potential Therapeutic Approach

“…Shailaja et al [220] showed that curcumin could reduce the level of C-reactive protein (CRP) and enhance the level of malondialdehyde (MDA), which play a favorable role in slowing aging by inhibiting the expression of age-related inflammatory cytokines. By using concentrations of 1 μM, 5 μM, 10 μM, and 20 μM, Pirmoradi et al [221] found the intervention effect of curcumin in rat adipose tissue-derived stem cells (rADSC) in vitro. Their results showed that curcumin could promote the proliferation of rADSC and reduce the senescence of adipose stem cells by promoting TERT gene expression.…”