Age-dependent cognitive decline, characterised by symptoms of memory impairments, deterioration of executive functions, as well as emotional and social disturbance, becomes more and more immanent and affects the quality of life of many senior citizens. The innovative research program RTG2413 SynAGE deals with the idea that cognitive decline in normal aging results from subtle synaptic alterations that impart an imbalance between stability and plastic properties of spine synapses and that is qualitatively different from neurodegeneration. This will further involve changes in the properties and functionality of the extracellular matrix, communication and interaction with glia cells and cells of the immune system, neuromodulation, and ultimately otherwise compensatory mechanisms. We aim to understand these processes of synaptic aging from a molecular, cellular as well as behavioral angle by jointly addressing transversal, intimately linked themes forming a comprehensive framework for inspiring thesis projects for 14 PhD and 14 MD students with high societal relevance.