Aging is the key risk factor for neurodegenerative diseases, and accumulation of the protein TDP-43 in neurons is a pathological feature of frontotemporal dementia and amyotrophic lateral sclerosis. However, the specific effect of aging on the protein TDP-43 has not been investigated. Researchers have now found in mice that interneuron degeneration occurs upon aging, and TDP-43 accelerates age-dependent neuronal degeneration, which may be related to the impaired memory of TDP-43 transgenic mice.