Relative Human Telomere Length Quantification qPCR Assay Kit

For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark1,2,3,4,5,6,7. Here we examined whether IL... More

For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark1,2,3,4,5,6,7. Here we examined whether IL-11, a pro-inflammatory cytokine of the IL-6 family, has a negative effect on age-associated disease and lifespan. As mice age, IL-11 is upregulated across cell types and tissues to regulate an ERK–AMPK–mTORC1 axis to modulate cellular, tissue- and organismal-level ageing pathologies. Deletion of Il11 or Il11ra1 protects against metabolic decline, multi-morbidity and frailty in old age. Administration of anti-IL-11 to 75-week-old mice for 25 weeks improves metabolism and muscle function, and reduces ageing biomarkers and frailty across sexes. In lifespan studies, genetic deletion of Il11 extended the lives of mice of both sexes, by 24.9% on average. Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%. Together, these results demonstrate a role for the pro-inflammatory factor IL-11 in mammalian healthspan and lifespan. We suggest that anti-IL-11 therapy, which is currently in early-stage clinical trials for fibrotic lung disease, may provide a translational opportunity to determine the effects of IL-11 inhibition on ageing pathologies in older people. Less

Cellular senescence is greatly accelerated by telomere shortening, and the steps forward in human aging are strongly influenced by environmental and lifestyle factors, wh... More

Cellular senescence is greatly accelerated by telomere shortening, and the steps forward in human aging are strongly influenced by environmental and lifestyle factors, whether DNA methylation (DNAm) is affected by exercise training, remains unclear. In the present study, we investigated the relationships between physiological functions, maximal oxygen uptake (VO2max), vertical jump, working memory, telomere length (TL) assessed by RT-PCR, DNA methylation-based estimation of TL (DNAmTL), and DNA methylation-based biomarkers of aging of master rowers (N = 146) and sedentary subjects (N = 95), aged between 37 and 85 years. It was found that the TL inversely correlated with chronological age. We could not detect an association between telomere length and VO2max, vertical jump, and working memory by RT-PCR method, while these physiological test results showed a correlation with DNAmTL. DNAmGrimAge and DNAmPhenoAge acceleration were inversely associated with telomere length assessed by both methods. It appears that there are no strong beneficial effects of exercise or physiological fitness on telomere shortening, however, the degree of DNA methylation is associated with telomere length. Less

Dexamethasone (Dex), a corticosteroid hormone, is used during the perinatal period to help fetal lung and other organ development. Conversely, Dex-induced cell proliferat... More

Dexamethasone (Dex), a corticosteroid hormone, is used during the perinatal period to help fetal lung and other organ development. Conversely, Dex-induced cell proliferation has been associated with accelerated aging. Using primary amnion epithelial cells (AECs) from term, not in labor, fetal membranes, we tested the effects of Dex on cell proliferation, senescence, and inflammation. Primary AECs treated with Dex (100 and 200 nM) for 48 h were tested for cell viability (crystal violet dye exclusion), cell cycle progression and/or type of cell death (flow cytometry), expression patterns of steroid receptors (glucocorticoid receptor, progesterone receptor membrane component 1&2), inflammatory mediators (IL-6 and IL-8), and telomere length (quantitative RT-PCR). Mechanistic mediators of senescence (p38MAPK and p21) were determined by western blot analysis. Dex treatment did not induce AEC proliferation, cell cycle, influence viability, or morphology. However, Dex caused dependent telomere length reduction and p38MAPK-independent but p21-dependent (confirmed by treatment with p21 inhibitor UC2288). Senescence was not associated with an increase in inflammatory mediators, which is often associated with senescence. Co-treatment with RU486 produced DNA damage, cell cycle arrest, and cellular necrosis with an increase in inflammatory mediators. The effect of Dex was devoid of changes to steroid receptors, whereas RU486 increased GR expression. Dex treatment of AECs produced nonreplicative and noninflammatory senescence. Extensive use of Dex during the perinatal period may lead to cellular senescence, contributing to cellular aging associated pathologies during the perinatal and neonatal periods. Less

Cell therapy may be regarded as a feasible alternative to whole organ transplantation to treat end-stage liver diseases. Human liver stem cells (HLSCs) are a population o... More

Cell therapy may be regarded as a feasible alternative to whole organ transplantation to treat end-stage liver diseases. Human liver stem cells (HLSCs) are a population of cells easily obtainable and expandable from a human adult liver biopsy. HLSCs share with mesenchymal stromal cells the same phenotype, gene expression profile, and differentiation capabilities. In addition, HLSCs show a specific commitment to the hepatic phenotype. Injection of HLSCs into immunodeficient mice fed with a methionine-choline-deficient diet to induce nonalcoholic steatohepatitis ameliorates liver function and morphology. In particular, HLSC treatment induced a reduction of liver fibrosis and inflammation at morphological and molecular levels. Moreover, HLSCs were able to persist for up to 3 weeks after the injection. In conclusion, HLSCs have healing effects in a model of chronic liver disease. Less

Background: The human telomerase reverse transcriptase (TERT) gene encodes the catalytic subunit of telomerase that is essential for maintenance of telomere length. We ai... More

Background: The human telomerase reverse transcriptase (TERT) gene encodes the catalytic subunit of telomerase that is essential for maintenance of telomere length. We aimed to find out whether variability within the TERT gene could be associated with telomere length and development of the disease in non-treated patients with chronic lymphocytic leukemia (CLL). Materials and methods: Telomere length, rs2736100, rs2853690, rs33954691, rs35033501 single-nucleotide polymorphisms, and variable number of tandem repeats (VNTR-MNS16A) were assessed in patients at diagnosis. In addition, blood donors served as controls for the polymorphism studies. Results: The minor rs35033501 A variant was more frequent among CLL patients than in healthy controls (OR=3.488, p=0.039). CLL patients over 60 years of age were characterized with lower disease stage at diagnosis (p=0.001 and p=0.008, for the Rai and Binet criteria, respectively). The MNS16A VNTR-243 short allele was more frequent in patients with a low disease stage (p=0.020 and p=0.028, for the Rai and Binet staging system) and also among older patients having longer telomeres (p=0.046). Patients with Rai 0–I stage were characterized with longer telomeres than those with more advanced disease (p=0.030). This relationship was especially pronounced in patients carrying the rs2736100 C allele, independently of the criteria used, ie, Binet (p=0.048) or Rai (p=0.001). Conclusion: Our results showed that the genetic variation within the TERT gene seems to play a regulatory role in CLL and telomere length. Keywords: telomere length, human telomerase reverse transcriptase, variable number of tandem repeats, single-nucleotide polymorphism, chronic lymphocytic leukemia Less

Curcumin is a biologically active polyphenol that exists in Indian spice turmeric. It has been reported that curcumin exerted anti-inflammatory, anti-oxidant and anti-can... More

Curcumin is a biologically active polyphenol that exists in Indian spice turmeric. It has been reported that curcumin exerted anti-inflammatory, anti-oxidant and anti-cancer effects in numerous in vitro and in vivo studies. However, it is not well-understood the molecular mechanism of curcumin for the cancer stem cells and telomerase in colorectal cancer. In this study, compound 19, a nitrogen-containing curcumin analog, was used to treat human colorectal cancer cells. Compound 19 showed a greater anti-proliferative activity than curcumin while displayed no significant toxicity toward normal human colon epithelial cells. Compound 19 exerted anti-inflammatory activities by deactivating STAT3 and NF-κB. In cancer stem cell populations, CD44, Oct-4 and ALDHA1 expressions were abolished upon treating with compound 19. Cancer stem cell biomarkers CD51 and CD133 positive populations were reduced and telomerase activities were decreased with the reduced STAT3 binding to hTERT promoters. This means compound 19 dually inhibits canonical and non-canonical functions of telomerase. Furthermore, compound 19 treatments induced cell cycle arrest at G1 phase and apoptosis. Human apoptosis-related array screening revealed that activated caspase 3, catalase, clusterin and cytochrome C led to apoptosis. Taken together, our data suggest that compound 19 can be a novel therapeutic agent for metastatic colorectal cancer by concurrently targeting STAT3 and NF-κB signaling pathways. Less

Long-term HIV infection, even with successful combination antiretroviral therapy (cART), is associated with an enhanced and accentuated onset of premature-aging or age-re... More

Long-term HIV infection, even with successful combination antiretroviral therapy (cART), is associated with an enhanced and accentuated onset of premature-aging or age-related diseases in people living with HIV (PLHIV). No data are available from low- and middle-income countries (LMICs) like India on inflamm-aging. In this study, we attempt to understand the relationshipbetween several ‘biomarkers’ of inflamm-aging in a well-defined Indian cohort of PLHIV. Blood samples were obtained from therapy naïve PLHIV (Pre-ART, n=43), patients on cART (ART, n=53) and age and gender-matched healthy controls (HC, n=41) after screening 714 individuals.We measured telomere length, 92 markers of inflammation, immune activation markers, and HIV-1 reservoir coupled with clinical phenotypes and neurocognitive function assessments using the International HIV Dementia Scale (IHDS). Despite a median duration of eight years of cART, sCD14 (p<0.001) and sCD163 (p=0.0377) was not normalized to the level of HC. Significant differences were observed in 11 inflammatory markers between HC and ART (p<0.05). Linear regression analysis showed a significant negative association of HIV-1 positive status on telomere length (−2.687, p<0.0001). There was a significant association between HIV status and higher odds of having IHDS≤10 (OR:39.74, p<0.0001). A significant negative association of CCL20 (−0.5236, p=0.0219) and CCL11 (−1.1608, p=0.0338) with HIV-1 reservoir was also observed. In conclusion, our study suggests that PLHIV on successful cART in a standardized public-health setting, may be at higher risk of inflamm-aging and age-related inflammatory diseases which may need special intervention and identifies several biomarkers for further mechanistic investigation. Less