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Gene Transcriptional Signatures in Healthy Ageing and Related Pathologies

Gene Transcriptional Signatures in Healthy Ageing and Related Pathologies 2020-2022
Acronym: GeT-SHARP
Budget: 431,900 RON
Project director: Robi Tacutu

The project aims to analyze and compare the age-related transcriptomics signatures in variuos tisues, both in healthy and pathological individuals, in order to identify shared or unique aging signature that drive aging or age-related diseases.

Abstract:

Aging is considered a major risk factor for the development of late-onset pathologies such as atherosclerosis, cancer, type 2 diabetes and neurodegenerative diseases. This suggests that age-related changes in gene expression should, to some extent, resemble the changes in gene expression observed in the above diseases. While the presence of common differentially- expressed genes is essential, this is not sufficient evidence to assume a common molecular basis for aging and ARDs. The important point is whether these genes display similar expression profiles as a whole. However, up until now, this question has not been fully addressed. In this study, we propose to analyze the age-related signatures of different human tissues (brain, muscle, lungs, kidney, and skin), compare them in order to get insights on whether the signatures are tissue-specific or whether there is a “common” aging signature across tissues. Additionally, we aim to search for similar-to-aging gene expression profiles among genetic screens of age-related pathologies. The identified pathological conditions with signatures similar to age-related transcriptional profiles of various tissues and cell types could then be used to build a dual aging-diseases centric model. This model could be extremely useful both at a theoretical level, for a better understanding of the mechanisms behind aging and diseases, as well as at an applicative level, for early-stage detection of late-onset diseases and related pathological conditions.

Project objectives:

The overall goal of the proposed research is to integratively study aging and age-related diseases and their common links at a genetic/molecular level. More specifically, the objectives are: 1) Building a joint model of age-related gene expression changes in different human tissues; 2) Investigating the particular genetic signatures and molecular pathways shared between aging and various age-related conditions with profiles similar to healthy aging; 3) Constructing an integrative model that describes the changes in gene expression in aging and in age-related diseases.

Estimated outcomes:

Upon the completion of the project, the following outcomes should be achieved: 1) the group will have a list of aging signatures and a ranked list of datasets based on their gene expression similarity to aging; 2) the group will build a gene network model aimed at explaining how the molecular components that determine the similarity to aging interact between themselves; 3) the group will have a graph model of physiological and pathological transitions occurring with age which could allow to make hypotheses and inferences about the aging process.

Robi Tacutu, Ph.D.
Robi Tacutu, Ph.D.

Group leader

A thorough, analytical and curiosity-driven scientist, with a multidisciplinary background in biology and computer science, Robi received his BSc in computer science from the University Politehnica Bucharest, and his MSc in biochemistry and molecular biology from the University of Bucharest. He has a long-term commitment and interest in the field of biogerontology (since 2005) and received his PhD in 2013 from the Ben-Gurion University of the Negev, in the lab of Prof. Vadim Fraifeld. His thesis was on an ageing-related topic: studying the relationships between aging and age-related diseases with the use of bioinformatics and network biology approaches, and More...

Dmitri Toren
Dmitri Toren

Assistant researcher

Dmitri is a bioinformatics researcher at the Institute of Biochemistry, focusing on curation for aging-related data, analysis of large screen datasets, dataset annotation and network-based analyses. He is also a Ph.D. cand More...

Gabriela Bunu, Mrs.
Gabriela Bunu, Mrs.

PhD student, Bioinformatics research assistant

Gabriela is a bioinformatics researcher at the Institute of Biochemistry, focussing on curation for aging-related data, analysis of large screen datasets and network-based analyses. She has a multidisciplinary background, More...