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What is SI-ADO-AGEING about?

SI-ADO-AGEING investigates how social stress during adolescence can increase the risk of cognitive decline later in life. While ageing is a natural process, the project explores how early-life experiences, particularly social isolation, can leave lasting marks on the brain—affecting how we learn, adapt, and age.

Adolescence is a sensitive period for brain development. Experiences during this time can shape how the brain responds to stress, how it forms and maintains neural connections, and how resilient it is to ageing. SI-ADO-AGEING is the first project to systematically investigate how adolescent stress contributes to long-term cognitive vulnerability—and how this can be reversed.

Scientific Focus

The project focuses on a unique population of neurons in the brain's hippocampus called adult-born dentate granule neurons (Adu-DGNs). These neurons are generated during adolescence and continue to integrate into memory circuits across the lifespan. SI-ADO-AGEING examines:

  • How social isolation during adolescence affects the development and function of Adu-DGNs
  • How this influences memory, mood, and cognitive flexibility during ageing
  • How stress-related hormones (like glucocorticoids) disrupt cellular health
  • How mitochondrial and metabolic dysfunction contribute to ageing vulnerability
  • Whether these changes can be reversed through targeted interventions

How will this be studied?

To address these questions, the project uses:

  • Animal models that mimic social isolation during adolescence
  • Behavioral tests to assess cognitive and emotional function across the lifespan
  • Large-scale Biosensors to record brain activity and network dynamics and build Connectivity maps
  • Molecular analyses of gene expression and stress markers
  • Metabolic profiling of brain cells, including mitochondrial function
  • Therapeutic interventions, including NAD+ precursors and selective GR modulators

What is the goal?

The ultimate goal of SI-ADO-AGEING is to:

  • Understand how adolescent stress imprints on the ageing brain
  • Identify multiscale biomarkers (molecular, cellular, circuit-level) of vulnerability and resilience
  • Test intervention strategies that can protect or restore brain function in ageing individuals
  • Provide a scientific foundation for preventive mental health strategies and future clinical translation

Why does it matter?

Cognitive decline and dementia are growing public health challenges. With over 150 million people projected to live with dementia by 2050, understanding early-life contributors is essential. SI-ADO-AGEING brings a preventive, life-course approach to brain health—focusing not only on ageing itself, but on the developmental roots of vulnerability.

This project directly supports the goals of ERA4Health and national European funding agencies, aiming to promote healthy cognitive ageing and inform evidence-based interventions.