Researchers at the Salk Institute have identified that neurons affected by cellular aging can drive brain inflammation in individuals with Alzheimer’s disease. The study appears in Cell Stem Cell and emphasizes aging as a contributor to neuroinflammation, expanding the traditional view that inflammation originates mainly from other cell types.
As cells age, they cease dividing and lose normal function, yet they do not necessarily die. The molecules shed by these aged cells can fuel chronic inflammation, a process tied to a range of conditions including cardiovascular disease and cancer. Earlier work suggested that these inflammatory cascades occurred primarily in dividing cells, not in neurons themselves. This new work shows that neurons can age and actively provoke inflammatory signaling within the brain, potentially increasing the risk of Alzheimer’s disease developing or worsening.
In their approach, researchers generated neurons from skin cells taken from people diagnosed with Alzheimer’s disease, turning epidermal cells into neurons in the lab to study aging and its underlying mechanisms. This model enabled them to observe how aged neurons behave and to identify the pathways that trigger inflammatory responses in neural tissue. The team demonstrated that aging neurons release inflammatory mediators that initiate a cascade of brain-damaging events. A neuron with an aged profile can still form numerous connections—often thousands—with nearby cells, meaning even a single aged neuron has the potential to influence the broader neural network. These findings were corroborated by examining aging markers and patterns of gene expression in brain tissue from twenty individuals who suffered from Alzheimer’s disease.
The scientists then explored a treatment strategy using a combination of drugs known to clear aging cells in other parts of the body, specifically dasatinib and quercetin. This senolytic cocktail reduced the number of aging neurons to levels comparable with younger, non-aging cells, suggesting that removing senescent cells in the brain could attenuate neuroinflammation and slow neurodegeneration in Alzheimer’s disease. The results offer a potential therapeutic avenue that focuses on senescent cell clearance to dampen harmful inflammatory signaling in neural tissue.
One important caveat highlighted by the researchers is the challenge of delivering senolytic therapies to the brain. The blood‑brain barrier can limit drug entry, meaning many compounds fail to reach effective concentrations in neural tissue. To address this, the team proposes screening existing medications with favorable brain‑penetration profiles or modifying candidates to cross the barrier more efficiently, while preserving safety. The ultimate goal is to develop brain-accessible treatments that replicate the anti‑inflammatory and anti‑degenerative benefits observed in their model systems.