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Aging of healthy humans is associated with a decreased expression of the IGF-1R and FOXO1 genes and with altered expression of their interacting miRNAs
9th Congress of the EUGMS / European Geriatric Medicine 4 (2013) S81–S141
Results.– Nonagenarians had the same ADL scores as octogenarians but their IADL scores were higher (P = 0.040). In univariate analyses, nonagenarians showed significative decrease in TREC compared to octogenarians (113.5 ± 18.4 vs. 180.5 ± 26.5, P < 0.05). There was no significant difference in telomere length (40.3 ± 2.1 vs. 43.5 ± 1.8, P = 0.25). Key conclusions.– Our data show that nonagenarians present telomere length and TREC with minimal decrease compared to octogenarians. The nonagenarians could be more robust regarding a better oxidative status and a slower decrease of their telomere and TREC number. Further research including a larger and more representative sample of patients is needed to confirm these data. http://dx.doi.org/10.1016/j.eurger.2013.07.328 P265
Aging of healthy humans is associated with a decreased expression of the IGF-1R and FOXO1 genes and with altered expression of their interacting miRNAs M. Budzinska a , M. Owczarz a , M. Roszkowska-Gancarz a , J. Polosak b , M. Puzianowska-Kuznicka a,b a Department of Geriatrics and Gerontology, CPME, Warsaw, Poland b Department of Human Epigenetics, MRC, Warsaw, Poland Introduction.– Decreased activity of the insulin and insulin-like growth factor-1 (IGF-1) pathways extends lifespan of model organisms. Certain polymorphic variants of genes encoding protein elements of these pathways are more common in long-lived than in young humans. Methods.– To check if aging is associated with changes of expression of the IGF-1R (IGF-1 receptor) and FOXO1 genes, and if this might be a result of altered regulation by miRNAs, we isolated total RNA from peripheral blood mononuclear cells (PBMCs) of young (Y, n = 59, 18–42 years), elderly (E, n = 55, 60–75 years), and of long-lived (L, n = 57, > 90 years) healthy individuals. Expression of the IGF-1R, FOXO1, miR-9, miR-96, miR-99a, miR-132, miR-145, and miR-182 was examined by SQ Real-Time PCR. Statistical analysis was performed using Kruskal-Wallis test and Spearman’s rank correlation coefficient. Results.– Expression of the IGF-1R and FOXO1 decreased with age (P = 0.0001 and P = 0.0001, respectively) in PBMCs of healthy humans. Expression of miR-96 and miR-145 increased (P = 0.0023 and P = 0.0330, respectively), while expression of miR-99a decreased with age (P = 0.0058). Expression of the IGF1R and FOXO1 negatively correlated with age (Rs = −0.478301, P = 0.0000001 and Rs = −0.414744, P = 0.00001, respectively). A weak negative correlation between the FOXO1 and miR-96 expression (Rs = −0.213021, P = 0.008864) was detected. Conclusion.– Healthy aging is associated with a significant decrease of expression of the IGF-1R and FOXO1 in PBMCs and this might be, at least in part, a result of epigenetic drift. Altered expression of these genes might affect function of PBMCs. http://dx.doi.org/10.1016/j.eurger.2013.07.329
P266
Healthy aging-related decrease of expression of the SIRT1 and SIRT3 might be a result of epigenetic drift M. Owczarz a,b , M. Budzinska a,b , M. Roszkowska-Gancarz a,b , J. Polosak b,c , M. Puzianowska-Kuznicka a,b,c a Department of Geriatrics and Gerontology, CPME, Warsaw, Poland
S101
b International Institute of Molecular and Cell Biology in Warsaw, Poland c Department of Human Epigenetics, MRC, Warsaw, Poland
Introduction.– Aging is a result of accumulation of stochastic damage to DNA and is associated with altered gene expression profile. Sirtuins play a role in DNA repair and in the regulation of gene expression. Overexpression or increased function of orthologs of SIRT1 and SIRT3 significantly extends lifespan of model organisms. Methods.– To evaluate the age-related changes of expression of the SIRT1 and SIRT3 and to analyze the epigenetic mechanisms underlying such changes, total RNA was isolated from human blood mononuclear cells (PBMCs) of young (Y, n = 57, 18–45 years), elderly (E, n = 51, 60–75 years), and long-lived (L, n = 56, 90–102 years) healthy individuals. Expression of the SIRT1, SIRT3, miR-34a, miR-145, miR-9, miR-28-5p, miR-132, and miR-199a-5p was analyzed by SQ real-time PCR. Statistical analysis was performed with Kruskal-Wallis test and Spearman’s rank correlation coefficient. Results.– Expression of the SIRT1 significantly decreased with age in PBMCs (P = 0.00001; P = 0.000001 for Y vs. E, P = 0.000001 for Y vs. L), as did expression of the SIRT3 (P = 0.00001; P = 0,000004 for Y vs. E, P = 0.000028 for Y vs. L). Expression of the SIRT1 and SIRT3 negatively correlated with age (Rs = −0.474250, P = 0.0000001 and Rs = −0.340688, P = 0,00001, respectively). Expression of miR-34a significantly increased with age (P = 0.00001). A weak negative correlations between the SIRT1 and miR-34a expression (Rs = −0.223132, P = 0.004970), and the SIRT1 and miR-132 (Rs = −0.169023, P = 0.032628) were detected. Conclusion.– Healthy aging is associated with the significant decrease of expression of the SIRT1 and SIRT3 in human PBMCs. This, at least in part, might be a result of increased expression of the selected miRNAs. http://dx.doi.org/10.1016/j.eurger.2013.07.330 P267
Klotho gene single nucleotide polymorphism is associated with the onset of stroke, hypertensive organ damages, and plasma klotho protein concentration O. Oguro a,b,c , K. Kamide a,b,c , N. Ito a,b,c , C. Nakama a,b,c , T. Kawai a,b,c , Y. Takeya a,b,c , K. Yamamoto a,b,c , K. Sugimoto a,b,c , K. Ikebe a,b,c , Y. Gondo a,b,c , M. Ohishi a,b,c , H. Rakugi a,b,c a Osaka University Graduate School of Medicine, Osaka, Japan b Osaka University Graduate school of Dentistry, Osaka, Japan c Osaka University Graduate School of Human Sciences, Osaka, Japan Introduction.– In human, klotho gene single nucleotide polymorphisms (SNPs) have been reported to be associated with coronary artery diseases and cardioembolisms. We have previously reported that klotho SNP (rs650439) was associated with carotid intimamedia thickness (IMT) in hypertensive patients. Although rs650439 (A/T) is assumed to be associated with cardiovascular events and organ damages, the details remain unknown. Here, we assessed whether rs650439 might be associated with the onset of cardiovascular diseases and hypertensive organ damages. Methods.– Five hundred and fifty-five patients with hypertension were analyzed for the association of rs650439 with cardiovascular events and hypertensive organ damages. We measured carotid IMT, left ventricular mass index (LVMI), carotid-femoral pulse wave velocity (cfPWV) for hypertensive organ damages. We measured plasma klotho protein concentration in 70 years elderly and assessed the relationship between rs650430 and plasma klotho protein concentration. Results.– In Kaplan-Meyer analysis, rs650439 was significantly associated with the onset of stroke, and the subjects with TT
Results.– Nonagenarians had the same ADL scores as octogenarians but their IADL scores were higher (P = 0.040). In univariate analyses, nonagenarians showed significative decrease in TREC compared to octogenarians (113.5 ± 18.4 vs. 180.5 ± 26.5, P < 0.05). There was no significant difference in telomere length (40.3 ± 2.1 vs. 43.5 ± 1.8, P = 0.25). Key conclusions.– Our data show that nonagenarians present telomere length and TREC with minimal decrease compared to octogenarians. The nonagenarians could be more robust regarding a better oxidative status and a slower decrease of their telomere and TREC number. Further research including a larger and more representative sample of patients is needed to confirm these data. http://dx.doi.org/10.1016/j.eurger.2013.07.328 P265
Aging of healthy humans is associated with a decreased expression of the IGF-1R and FOXO1 genes and with altered expression of their interacting miRNAs M. Budzinska a , M. Owczarz a , M. Roszkowska-Gancarz a , J. Polosak b , M. Puzianowska-Kuznicka a,b a Department of Geriatrics and Gerontology, CPME, Warsaw, Poland b Department of Human Epigenetics, MRC, Warsaw, Poland Introduction.– Decreased activity of the insulin and insulin-like growth factor-1 (IGF-1) pathways extends lifespan of model organisms. Certain polymorphic variants of genes encoding protein elements of these pathways are more common in long-lived than in young humans. Methods.– To check if aging is associated with changes of expression of the IGF-1R (IGF-1 receptor) and FOXO1 genes, and if this might be a result of altered regulation by miRNAs, we isolated total RNA from peripheral blood mononuclear cells (PBMCs) of young (Y, n = 59, 18–42 years), elderly (E, n = 55, 60–75 years), and of long-lived (L, n = 57, > 90 years) healthy individuals. Expression of the IGF-1R, FOXO1, miR-9, miR-96, miR-99a, miR-132, miR-145, and miR-182 was examined by SQ Real-Time PCR. Statistical analysis was performed using Kruskal-Wallis test and Spearman’s rank correlation coefficient. Results.– Expression of the IGF-1R and FOXO1 decreased with age (P = 0.0001 and P = 0.0001, respectively) in PBMCs of healthy humans. Expression of miR-96 and miR-145 increased (P = 0.0023 and P = 0.0330, respectively), while expression of miR-99a decreased with age (P = 0.0058). Expression of the IGF1R and FOXO1 negatively correlated with age (Rs = −0.478301, P = 0.0000001 and Rs = −0.414744, P = 0.00001, respectively). A weak negative correlation between the FOXO1 and miR-96 expression (Rs = −0.213021, P = 0.008864) was detected. Conclusion.– Healthy aging is associated with a significant decrease of expression of the IGF-1R and FOXO1 in PBMCs and this might be, at least in part, a result of epigenetic drift. Altered expression of these genes might affect function of PBMCs. http://dx.doi.org/10.1016/j.eurger.2013.07.329
P266
Healthy aging-related decrease of expression of the SIRT1 and SIRT3 might be a result of epigenetic drift M. Owczarz a,b , M. Budzinska a,b , M. Roszkowska-Gancarz a,b , J. Polosak b,c , M. Puzianowska-Kuznicka a,b,c a Department of Geriatrics and Gerontology, CPME, Warsaw, Poland
S101
b International Institute of Molecular and Cell Biology in Warsaw, Poland c Department of Human Epigenetics, MRC, Warsaw, Poland
Introduction.– Aging is a result of accumulation of stochastic damage to DNA and is associated with altered gene expression profile. Sirtuins play a role in DNA repair and in the regulation of gene expression. Overexpression or increased function of orthologs of SIRT1 and SIRT3 significantly extends lifespan of model organisms. Methods.– To evaluate the age-related changes of expression of the SIRT1 and SIRT3 and to analyze the epigenetic mechanisms underlying such changes, total RNA was isolated from human blood mononuclear cells (PBMCs) of young (Y, n = 57, 18–45 years), elderly (E, n = 51, 60–75 years), and long-lived (L, n = 56, 90–102 years) healthy individuals. Expression of the SIRT1, SIRT3, miR-34a, miR-145, miR-9, miR-28-5p, miR-132, and miR-199a-5p was analyzed by SQ real-time PCR. Statistical analysis was performed with Kruskal-Wallis test and Spearman’s rank correlation coefficient. Results.– Expression of the SIRT1 significantly decreased with age in PBMCs (P = 0.00001; P = 0.000001 for Y vs. E, P = 0.000001 for Y vs. L), as did expression of the SIRT3 (P = 0.00001; P = 0,000004 for Y vs. E, P = 0.000028 for Y vs. L). Expression of the SIRT1 and SIRT3 negatively correlated with age (Rs = −0.474250, P = 0.0000001 and Rs = −0.340688, P = 0,00001, respectively). Expression of miR-34a significantly increased with age (P = 0.00001). A weak negative correlations between the SIRT1 and miR-34a expression (Rs = −0.223132, P = 0.004970), and the SIRT1 and miR-132 (Rs = −0.169023, P = 0.032628) were detected. Conclusion.– Healthy aging is associated with the significant decrease of expression of the SIRT1 and SIRT3 in human PBMCs. This, at least in part, might be a result of increased expression of the selected miRNAs. http://dx.doi.org/10.1016/j.eurger.2013.07.330 P267
Klotho gene single nucleotide polymorphism is associated with the onset of stroke, hypertensive organ damages, and plasma klotho protein concentration O. Oguro a,b,c , K. Kamide a,b,c , N. Ito a,b,c , C. Nakama a,b,c , T. Kawai a,b,c , Y. Takeya a,b,c , K. Yamamoto a,b,c , K. Sugimoto a,b,c , K. Ikebe a,b,c , Y. Gondo a,b,c , M. Ohishi a,b,c , H. Rakugi a,b,c a Osaka University Graduate School of Medicine, Osaka, Japan b Osaka University Graduate school of Dentistry, Osaka, Japan c Osaka University Graduate School of Human Sciences, Osaka, Japan Introduction.– In human, klotho gene single nucleotide polymorphisms (SNPs) have been reported to be associated with coronary artery diseases and cardioembolisms. We have previously reported that klotho SNP (rs650439) was associated with carotid intimamedia thickness (IMT) in hypertensive patients. Although rs650439 (A/T) is assumed to be associated with cardiovascular events and organ damages, the details remain unknown. Here, we assessed whether rs650439 might be associated with the onset of cardiovascular diseases and hypertensive organ damages. Methods.– Five hundred and fifty-five patients with hypertension were analyzed for the association of rs650439 with cardiovascular events and hypertensive organ damages. We measured carotid IMT, left ventricular mass index (LVMI), carotid-femoral pulse wave velocity (cfPWV) for hypertensive organ damages. We measured plasma klotho protein concentration in 70 years elderly and assessed the relationship between rs650430 and plasma klotho protein concentration. Results.– In Kaplan-Meyer analysis, rs650439 was significantly associated with the onset of stroke, and the subjects with TT