A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring
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PROVIDER: PRJNA1159803 | ENA |
REPOSITORIES: ENA
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Project description:Centenarians provide a unique lens through which to study longevity, healthy aging, and resiliency. Moreover, models of human aging and resilience to disease that allow for the testing of potential interventions are virtually non-existent. We obtained and characterized over 86 centenarian and offspring peripheral blood samples including those connected to functional independence data highlighting resistance to disability and cognitive impairment. Targeted methylation arrays were used in molecular aging clocks to compare and contrast differences between biological and chronological age in these specialized subjects. Isolated peripheral blood mononuclear cells (PBMCs) from 20 of these subjects were then successfully reprogrammed into high-quality induced pluripotent stem cell (iPSC) lines which were functionally characterized for pluripotency, genomic stability, and the ability to undergo directed differentiation. The result of this work is a one-of-a-kind resource for studies of human longevity and resilience that can fuel the discovery and validation of novel therapeutics for aging-related disease.
2024-09-25 | GSE276957 | GEO
Project description:In this study, we employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. With data from 26.7 million reads comprising 9.4x108 bp from 3 centenarian and 3 control individuals, we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls.
2012-06-01 | GSE32493 | GEO
Project description:In this study, we employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. With data from 26.7 million reads comprising 9.4x108 bp from 3 centenarian and 3 control individuals, we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls. Examination of miRNA profile of two different ages
2012-06-01 | E-GEOD-32493 | biostudies-arrayexpress
Project description:The role of epigenetics in the modulation of longevity has not been studied in humans. To this aim, (1) we evaluated the DNA methylation from peripheral leukocytes of 21 female centenarians, their 21 female offspring, 21 offspring of both non-long-lived parents, and 21 young women through ELISA assay, pyrosequencing analysis of Alu sequences, and quantification of methylation in CpG repeats outside CpG islands; (2) we compared the DNA methylation profiles of these populations through Infinium array for genome-wide CpG methylation analysis. We observed an age-related decrease in global DNA methylation and a delay of this process in centenarians' offspring. Interestingly, literature data suggest a link between the loss of DNA methylation observed during aging and the development of age-associated diseases. Genome-wide methylation analysis evidenced DNA methylation profiles specific for aging and longevity: (1) aging-associated DNA hypermethylation occurs predominantly in genes involved in the development of anatomical structures, organs, and multicellular organisms and in the regulation of transcription; (2) genes involved in nucleotide biosynthesis, metabolism, and control of signal transmission are differently methylated between centenarians' offspring and offspring of both non-long-lived parents, hypothesizing a role for these genes in human longevity. Our results suggest that a better preservation of DNA methylation status, a slower cell growing/metabolism, and a better control in signal transmission through epigenetic mechanisms may be involved in the process of human longevity. These data fit well with the observations related to the beneficial effects of mild hypothyroidism and insulin-like growth factor I system impairment on the modulation of human lifespan.
| S-EPMC3776126 | biostudies-literature
Project description:Gut microbiota markers associated with lifestyle and diet in extreme longevity: focus on Sardinian healthy centenarians
| PRJEB52843 | ENA
Project description:Gut microbiota markers associated with lifestyle and diet in extreme longevity: focus on Sardinian healthy centenarians
| PRJEB52630 | ENA
Project description:We performed a transcriptomic analysis of mononuclear cells in blood in young people, septuagenarians, and centenarians.
2021-01-17 | E-MTAB-9988 | biostudies-arrayexpress
Project description:Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) derived from seven centenarians (CEN), six centenarians' offspring (CO), and nine offspring spouses or neighbors (Control, age-matched to CO) are performed to investigate the shared immune features between CEN and CO. The results indicate that among all 12 T cell clusters, the cytotoxic-phenotype-clusters (CPC) and the naïve-phenotype-clusters (NPC) significantly change between CEN and ontrol. Compared to Control, both CEN and CO are characterized by depleted NPC and increased CPC, which is dominated by CD8+ T cells. Furthermore, CPC from CEN and CO share enhanced signaling pathways and transcriptional factors associated with immune response, and possesse similar T-cell-receptor features, such as high clonal expansion. Interestingly, rather than a significant increase in GZMK+ CD8 cells during aging, centenarians show accumulation of GZMB+ and CMC1+ CD8 T cells. Collectively, this study unveils an immune remodeling pattern reflected by both quantitative increase and functional reinforcement of cytotoxic T cells which are essential for healthy aging.
| S-EPMC9799020 | biostudies-literature
Project description:Biomarkers of familial longevity may represent mechanisms underlying healthy aging. To identify gene expression profiles marking human familial longevity, an explorative genome-wide expression study was performed among 50 families from the Leiden Longevity Study who have a life-long survival advantage of 30%. Gene expression profiles were compared between 50 nonagenarians (mean age 93.4 years) and 50 controls (mean age 61.9 years) to investigate differential gene expression that may arise as a function of both chronological age and familial longevity. Differential expression was observed for 2953 probes (FDR≤0.05) and for 109 GO terms, which corresponded well with previously reported findings on gene expression changes associated with chronological age, such as ‘immune response’, ‘signal transduction’ and ‘regulation of gene transcription’. To explore which of the 2953 chronological age-related probes also marked familial longevity, we compared gene expression profiles of 50 offspring of the nonagenarians (mean age 60.8 years) with the same 50 controls. Since the average gene expression levels did not differ between offspring and controls, we tested for differential expression as a function of age (age range 43-79 years). We identified 360 probes (FDR≤0.1) and the ‘Rho protein signal transduction’ GO biological process (FWER = 0.079) whose expression signatures marked familial longevity already at middle-age. Of these probes, 236 were annotated and represent 244 known genes, including WRN and MYC. Interestingly, 51 genes are involved in the regulation of gene expression. Further investigation into the genes involved may be important for unraveling mechanisms underlying longevity.
2011-09-04 | GSE16717 | GEO
Project description:We established induced pluripotent stem cells (iPSC) from centrenarians by retroviral transduction of primary human fibroblasts. To show the similarity between 201B7 iPSC and 100-1 #16 iPSC (induced pluripotent stem cells from centenarian), this experiment was designed.
2012-09-01 | GSE36667 | GEO