Proteomic Insights into Brain Aging: The Sheep as a Translational Model.
The progressive aging of the population represents a major challenge for modern medicine and society.
As life expectancy increases, understanding the biological mechanisms of brain aging becomes crucial, since age-related molecular and structural alterations lead to cognitive decline, increased vulnerability to neurodegeneration and reduced neural plasticity.
Traditionally, studies on brain aging have relied on human and rodent models. However, rodents’ limited brain complexity and lifespan reduce their translational relevance.
Among large mammals, sheep have recently gained attention as an alternative model for neuroscience due to their gyrencephalic brains, longer lifespan and well-characterized cortical regions involved in vision and motor control.
The availability of brain tissue from different life stages, combined with behavioural and physiological data, makes sheep a valuable model for investigating molecular and functional mechanisms of brain aging in a translational perspective.
The aim of this project is to investigate the molecular mechanisms underlying brain aging using sheep as a translational model.
The study will focus on the analysis of brain regions particularly affected by aging — hippocampus, motor cortex, and prefrontal cortex— by applying both untargeted and targeted proteomic approaches.
Additionally, matched blood and saliva samples will be analysed to identify circulating and salivary biomarkers that mirror molecular changes occurring in the brain.
Specific objectives of this research project are:
1. To map proteomic changes in brain regions critical for aging, such as the hippocampus, motor cortex and prefrontal cortex using a nano-LC-ESI-MS/MS with a high-resolution Orbitrap system.
2. To obtain an integrated dataset combining molecular, anatomical and behavioural findings, providing a multi-level view of how aging affects the animal as a whole.
3. To compare the sheep proteomic signatures with available human and rodent datasets, assessing their translational relevance.
4. To identify potential peripheral biomarkers in blood and saliva that reflect central proteomic changes, although this remains challenging due to the variability of biological fluids.
In conclusion, this project integrates untargeted discovery, targeted validation and multi-fluid proteomics, combined with advanced bioinformatics, to study brain aging in sheep in different age stages.
By leveraging the unique advantages of this model, I aim to produce results that are not only scientifically novel, but also translationally relevant — with potential benefits for both human medicine and veterinary sciences.
October 2024 – July 2025 Giovani Promettenti Scholarship “Project: Proteomic analysis of the brain during aging, stress, and neurodegeneration” (UNIMI).
MA in Scienze Biotecnologiche Veterinarie (SBV) at the University of Milan (UNIMI) in 2024 with the final evaluation of 110/110 cum laude.
Master thesis entitled “Insights into L-Serine Synthesis Pathway in hiPSC-derived Astrocytes”; this study aims to investigate astrocyte’s differentiation and L-Serine’s role in astrocyte-central nervous system and its implication in the progression of neurodegenerative disease.
Around this time, I attended Department of Veterinary Medicine and Animal Sciences (Biochemistry Section) at the University of Milan.
BA in Biotecnologia at the University of Milan (UNIMI) in 2021.
Traineeship activity at the Department of Pharmacological and Biomolecular Sciences, at the University of Milan.
The thesis project aimed to induce a state of high plasticity in terminally differentiated human fibroblasts, without the use of exogenous vectors or epigenetic modifiers.
The goal was to avoid the use of stably pluripotent cells, which are particularly prone to tumorigenic behaviours, exposing cells to controlled cryogenic temperatures.
Publications: Orcid
Supervisor Dr. Elisa Margherita Maffioli
Co-supervisor Prof. Gabriella Tedeschi
