Leader: Veronica De Rosa (CNR); Other collaborator(s): Antonietta Liotti (CNR)
Over the last decades, extended life expectancy has been paralleled by progressive ageing and a marked increase in the prevalence of age-related diseases (ARDs), such as obesity and type 2 diabetes (T2D). Dysfunction of the adipose tissue (AT) is widely recognized as a significant hallmark of the ageing process that, in turn, results in an elevated risk of obesity and T2D onset. The objective of this task is to evaluate how and when, through life, epigenetic mechanisms such as DNA methylation can induce cellular senescence in AT, favoring the progression of ARDs. To this aim, we will:
Brief description of the activities and of the intermediate results: Postdoc research position announced. Participation in Age-It General Meeting (20-21 May 2024, Venice) with a scientific work entitled: “Methylome analysis of adipose precursor cells (APC) of First-degree relatives (FDR) of type 2 diabetes (T2D) subjects” accepted as an oral presentation. Scientific update: In order to define the epigenetic "signature" responsible for premature senescence in the adipocyte precursor cells (APC) of subjects with a family history of type 2 diabetes (First Degree Relatives, FDRs), an integrative analysis was carried out of the APC methylome data of the aforementioned individuals with data available in the database of genes related to human aging (The Human Aging Genomic Resources; https://genomics.senescence.info/). In parallel, we are proceeding with the enrollment of healthy control subjects for the validation of the gating strategy using flow cytometric analyzes for the study of senescent lymphocyte populations. In particular, we are evaluating the frequency of CD4+ T lymphocytes which are characterized by a characteristic phenotype given by the reduction of CD27 and CD28 markers, with the simultaneous increase of CD57, KLRG-1 and CD45RA markers.
Update: Conclusion of the recruitment procedure and related activation of a 12-month research fellowship position. Scientific update: The integrative analysis of the APC methylome of subjects with a family history of diabetes with the data available in the database of genes related to human aging (see previous update) highlighted an enrichment of the genes involved in the p53 pathway. The data obtained were presented at the Age-It General Meeting (20-21 May 2024, Venice). At the same time, we are continuing with the recruitment of healthy control subjects for the study of senescent lymphocyte populations by flow cytometry.
Dissemination: General Meeting Age-it, Università Ca' Foscari, Venice: Methylome analysis of adipose precursor cells (APCs) of First degree relatives (FDR) of type 2 Diabetic (T2D) subjects Venice, 20-22 May 2024 (presented by : Veronica De Rosa)
New start of the procedure for the selection of the research grant due to the non-acceptance of the previous candidate. The selection of the candidate will take place between September and October. From an experimental point of view we have worked on the development of the techniques for the isolation of senescent cells from peripheral blood of healthy controls.
Finalization of the selection procedure for a 15-month research fellowship position.
Scientific update: We have started the recruitment of a new cohort of patients composed of obese subjects with or without diabetes. Using FACS analysis, we will perform the same immune-senescent profiling as for Type 2 diabetic patients, evaluating CD27, CD28, CD57, KLRG-1, and CD45RA cellular surface markers. Starting from purified CD4+CD25- T lymphocytes, we are evaluating by Western blot analysis intracellular signaling pathways of proteins known to be involved in cellular senescence, such as p53, p16, p21. In addition, we are setting up the protocol for evaluating the SA- β-Gal activity by flow cytometry.
Published Paper: Fusco C et al., Sci Adv. doi: 10.1126/sciadv.adr7934.
Published Paper: Fusco C et al., Sci Adv. doi: 10.1126/sciadv.adr7934.
Dissemination: General Meeting Age-it, Università Ca' Foscari, Venice: Methylome analysis of adipose precursor cells (APCs) of First degree relatives (FDR) of type 2 Diabetic (T2D) subjects Venice, 20-22 May 2024 (presented by : Veronica De Rosa)