Unwanted loneliness has become one of the major challenges of modern society. Beyond its clear psychological and emotional impact, there is growing scientific evidence that social isolation produces functional changes in the brain, which become even more pronounced in later stages of life.
Although many older adults develop remarkable emotional stability, often linked to a proactive and healthy lifestyle, aging also increases vulnerability to stressful situations. This reduced resilience is often associated with difficulties in adapting and with the appearance of depressive symptoms. Factors such as family estrangement, the loss of friends or a spouse, mobility problems, and physical or cognitive decline are some of the causes that gradually lead a person into isolation, making it one of the main risk factors for mental health problems in old age.
But what happens in the brain when an older person becomes disconnected from society? To answer this question, we designed a series of experiments using aged mouse models. We observed that social isolation produces behavioral alterations, which we analyzed using Artificial Intelligence to obtain broader and more precise assessments. These changes were associated with depressive symptoms, anxiety-like behaviors, and cognitive decline. In addition, we detected significant physiological changes, including modifications in neurotransmission and effects on brain plasticity in key regions such as the prefrontal cortex, the hippocampus, and especially the amygdala, which became the main focus of our study.
One of the research priorities was the study of perineuronal nets (PNNs), specialized extracellular matrix structures that form a mesh-like network around certain neurons. Among their functions are neuronal protection and the regulation of brain plasticity. In other words, they can either facilitate or hinder the connectivity of the neurons they surround depending on the size of the openings in the network: larger openings allow greater plasticity, while smaller openings reduce it. This mechanism regulates the brain’s ability to reorganize itself and adapt to life’s circumstances.
We found that isolation alters these networks, particularly in females, causing changes in neuronal activity, neuronal connectivity, and emotional behavior. The results also revealed that some of these alterations could be reversed through resocialization.
Furthermore, we artificially modified plasticity through stereotaxic surgery by breaking down PNNs with enzymes, allowing us to compare whether this artificial alteration correlates behaviorally with the changes produced by isolation. This approach may help determine whether pharmacological manipulation of PNNs could be used to alter brain plasticity.
Finally, we are using technologies such as DREADDs and MiniScope, which make it possible to manipulate neuronal activity and record it in vivo in real time. These tools will allow us to understand with great precision how specific neurons participate in emotions such as fear, anxiety, and resilience to stress.
Our study demonstrates that the brain changes when close personal relationships disappear. Therefore, combating isolation in older adults is not only about improving psychological well-being but also about protecting brain health. After all, our life experiences, learning, and social relationships are fundamental components of who we are.
Graduated with a degree in Psychology in 2019 from Universitat Jaume I. He is currently completing his PhD in Biomedicine at the same university, specializing in Anatomy and Embryology, under the supervision of Esther Castillo Gómez, Principal Investigator of the Neuropathology and Brain Plasticity research group.