Leader: Giuseppe Passarino (UNICAL); Other collaborator(s): Alberto Montesanto, Paolina Crocco, Giuseppina Rose, Francesco De Rango, Dina Bellizzi, Patrizia D'Aquila, Giada Sena, Teresa Serra Cassano.
The present task, by taking advantage of previous and current sampling campaigns of the proposers and of partners, will dissect the mechanism of epigenetic clocks and of additional epigenetic markers to get insights on the molecular aspects of the ageing process and on how it can be manipulated to improve both lifespan and healthspan. To this purpose, epigenetic modifications associated to ageing and to different interventions which have been previously identified to have important effects on delaying ageing, such as calorie restriction, will be evaluated (together with physiological and biochemical parameters) in large samples for which up to 20 years of follow up data are available.
Brief description of the activities and of the intermediate results: The group of researchers involved in this task, are currently carrying out a sampling campaign which will give the possibility to analyze samples which have conducted different diet regimes. Of note is the presence in the samples which is currently gathered of subjects which conducted for 6 months a Mimicking Fasting Diet, that is a diet which has been reported to have effects close to calorie restriction when hallmarks of ageing are considered. Moreover, subjects of different ages previously collected and defined for a number of phenotypic features and with a follow up of about 20 years, will be analyzed by the EPIC analysis. Finally, in collaboration with the CNR unit of Piano Lago, this unit will analyze samples of AD (Alzheimer Disease) patients and samples of FTD (Fronto Temporal Dementia) Patients. The first AD samples have been analyzed in order to evaluate the quality of the DNA. The results were quite encouraging.
The analysis of epigenetic variation and of the transcriptomic modulation is also carried out on microorganisms, in order to verify possible conserved pathways.
EPIC analysis of AD samples and controls have continued, as well as the sampling campaign to recruit samples with different diets. In parallel, the methylation analysis of subjects of different ages led to the definition of a group of methylation sites which are able to define with a very significant approximation the real age of a subject. These results are being submitted for publication in forensic genetics journals, as they can be considered very important in this field because they represent a tool to estimate the age of an unknown subject by using a number of sites much lower than it is currently used. This will allow many labs, which have limited resources, to carry out such analysis. On the other hand, the analysis has highlighted that methylation sites are significantly modulated by cronological age and that, although the total result is close to the cronological age, the analysis of single sites can give important hints on specific modulation of the methilation correlated to specific phenotypic features. The analysis continues on further samples for the definition of differently methylated areas to identify the genes that modulate their expression in different situations of neurodegeneration.
The analysis of the epigenetic modulation in microorganisms showed the effect of essential oils on the methylation and on antibiotic resistance.
The EPIC analysis of AD samples (in collaboration with CNR Piano Lago) and controls as well as that of ultra-nonagenarians has been completed (480 samples in total). The data have all been classified and will be analyzed in the coming months. The first descriptive analyses are currently underway while waiting to undertake more in-depth analyses. Sampling, DNA extraction and analysis of further samples continue to define the differently methylated areas in different nutritional situations.
In order to take the analysis of individual variability at old age further, fecal samples of old subjects living in a nursery house have been collected and will soon be analyzed.
The sampling of subjects with different nutritional style went on during the period Otober-December 2024. The analysis of the previous data on ultranonaenarians has provided some preliminary results regarding the genes and the pathways which can be considered of interest when it comes to epigentic modulation of ageing. The analysis is continuing but these preliminary results have allowed the preparation of a ms. where we describe a new epigenetic clock based on 5 genes only. The ms. has been submitted for Publication.
A meeting has been organized on the 3-4 October to report the preliminary data and results emerged from the tasls of the project carried out at University of Calabria. The meeting allowed to talk, and discuss the results with, the main local stakeholders of the project, such as the Department of Geriatrics and AUSER (https://www.unical.it/contents/calendars/view/eventi-unical/2584).
The sampling of subjects with different nutritional style is close to the end and the methylation analysis is going on. The analysis of the previous data on ultranonaenarians has provided some preliminary results regarding the genes and the pathways which can be considered of interest when it comes to epigentic modulation of ageing. The ms. where we describe a new epigenetic clock based on 5 genes only has been accepted for publication. A new study correlating methylation profiles, telomere length and telomere related miRNA has been started taking advantage of previously accumulated data and should be completed within a few months.
D'Aquila P, De Rose E, Sena G, Scorza A, Cretella B, Passarino G, Bellizzi D. Quorum Quenching Approaches against Bacterial-Biofilm-Induced Antibiotic Resistance. Antibiotics (Basel). 2024 Jul 3;13(7):619. doi: 10.3390/antibiotics13070619.
Sena G, De Rose E, Crudo M, Filippelli G, Passarino G, Bellizzi D, D'Aquila P. Essential Oils from Southern Italian Aromatic Plants Synergize with Antibiotics against Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis Cell Growth and Biofilm Formation. Antibiotics (Basel). 2024 Jun 28;13(7):605. doi: 10.3390/antibiotics13070605.
Crocco P, Dato S, La Grotta R, Passarino G, Rose G. Evidence for a relationship between genetic polymorphisms of the L-DOPA transporter LAT2/4F2hc and risk of hypertension in the context of chronic kidney disease.BMC Med Genomics. 2024 Jun 18;17(1):163. doi: 10.1186/s12920-024-01935-2.
Crocco P, De Rango F, Bruno F, Malvaso A, Maletta R, Bruni AC, Passarino G, Rose G, Dato S.Genetic variability of FOXP2 and its targets CNTNAP2 and PRNP in frontotemporal dementia: A pilot study in a southern Italian population. Heliyon. 2024 May 22;10(11):e31624. doi: 10.1016/j.heliyon.
Giacconi R, D'Aquila P, Cardelli M, Piacenza F, Pierpaoli E, Sena G, Di Rosa M, Bonfigli AR, Galeazzi R, Cherubini A, Fedecostante M, Sarzani R, Di Pentima C, Giordano P, Antonicelli R, Lattanzio F, Passarino G, Provinciali M, Bellizzi D. Blood circulating bacterial DNA in hospitalized old COVID-19 patients. Immun Ageing. 2023 Dec 18;20(1):76.
Crocco P, De Rango F, Dato S, La Grotta R, Maletta R, Bruni AC, Passarino G, Rose G. The Shortening of Leukocyte Telomere Length Contributes to Alzheimer's Disease: Further Evidence from Late-Onset Familial and Sporadic Cases. Biology (Basel). 2023 Sep 26;12(10):1286. doi:10.3390/biology12101286. PMID:
Organizzazione Convegno: Salute pubblica ed invecchiamento in Calabria- La ricerca UNICAL nel Progetto PNRR AGE-IT / Giornate di Studio ed Approfondimento. 3-4 Ottobre, Università della Calabria. Il programma è disponibile al link: https://www.unical.it/media/publications_attachments/14399/Brochure_Age_it_Calabria.pdf