Evaluation of Electroencephalographic Biomarkers in Physiological Aging (AGE-MARK)

Investigating Brain Connectivity and Complexity as Biomarkers of Healthy Aging and Brain Rejuvenation by Stem Cell-derived Exosomes

Aging is the inevitable biological process that results in a progressive structural and functional decline from the cellular level to whole body function. It is associated with functional changes in the resting brain activity, brain morphology, plasticity, complexity and function. Moreover, aging is the main risk factor for neurodegenerative disease.

Understanding the molecular mechanisms underlying the age-related neurophysiological changes and identifying novel biomarkers of healthy brain ageing is thus instrumental for the development of efficient interventions against age-related motor/cognitive impairments. Within this context, there is now a significant literature establishing the enhanced efficacy of secreted exosomes over the stem cells from which they are derived when used as a possible treatment for neurodegenerative disorders. Exosomes are a subgroup of extracellular vesicles which regulate intercellular communication and, unlike stem cells, easily cross into the brain and can be administered in non-syngeneic species without immune rejection.

Studies on brain ageing in humans has major limitation in the lack of accessibility of the central nervous system. EEG has allowed the non-invasive assessment of functional changes in the aging brain. In fact, this technique can provide a direct assessment of neural activity and information flow with a higher temporal resolution that is particularly important for investigating the dynamics of brain changes underlying cognitive processing and age-related changes, providing novel biomarkers of brain aging that could be used to unveil differences between healthy and unhealthy processes particularly in the pre-symptomatic and pre-clinical stage. To reach this aim, it is necessary to demonstrate, in experimental models, the relationship between age-dependent changes in brain activity and cellular/molecular processes occurring in aged brain.

Our project will pursue this overall goal by:

1) identifying neurophysiological biomarkers of brain aging in human subjects based on functional network and complexity analyses; 2) characterizing age-dependent changes in brain connectivity and complexity in mice and correlating them to changes in motor and cognitive performances and to molecular alterations occurring in both the brain and blood; 3) evaluating changes of the identified electrophysiological and molecular biomarkers in mice treated with stem cell derived exosomes for the rejuvenation of the aged brain.

4) designing Artificial Intelligence (AI) predictor of brain age trajectories on individual basis to evaluate individual neural reserve and resilience.

This study will identify novel electrophysiological biomarkers of healthy brain ageing and will advance knowledge on cellular/molecular signature of brain aging that could targeted for the preservation of brain health.

Study Overview

• Status: Recruiting
• Conditions: Aging

• Study Type: Observational
• Enrollment (Estimated): 96

Contacts and Locations

• Study Contact: Name: Lucia Gatta, PhD; Phone Number: +390652253440; Email: lucia.gatta@sanraffaele.it

Study Locations

• Italy
  • Rome
    • Rome, Rome, Italy, 00166
      • Recruiting
      • IRCCS San Raffaele Roma
      • Contact: Fabrizio Vecchio; Phone Number: 3478031201; Email: fabrizio.vecchio@sanraffaele.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

A total of 96 subjects (divided in 32 young (20-40 years), 32 adult (40-60 years), 32 elderly subjects (> 60 years) matched for gender and education) will be enrolled and undergo to EEG recording

Description

Inclusion Criteria:

• healthy subjects
• > 18 years old

Exclusion Criteria:

• neurological disorders
• head injuries,
• substance abuse,
• psychiatric conditions
• any medications affecting the cardiovascular or central nervous systems

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Sub

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identification of Novel Biomarkers and Interventions for Healthy Brain Ageing	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele Roma

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2023
• Primary Completion (Estimated): April 20, 2026
• Study Completion (Estimated): October 19, 2026

Study Registration Dates

• First Submitted: January 29, 2025
• First Submitted That Met QC Criteria: February 12, 2025
• First Posted (Actual): February 13, 2025

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: RP 23/10

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No