Overview
- Analyzing 38 postmortem hippocampi with paired single-nucleus RNA sequencing and chromatin-accessibility profiling (~356,000 nuclei), researchers reported a distinct molecular profile in superagers.
- Superagers showed roughly twice the abundance of immature neurons compared with typical older adults and about 2.5 times that of people with Alzheimer’s disease, with a significant difference versus the Alzheimer’s group.
- Brains from individuals with Alzheimer’s displayed fewer neuroblasts and immature neurons alongside an accumulation of stem-cell–like cells that appeared unable to mature.
- Group differences were driven largely by chromatin accessibility rather than gene-expression levels, with superagers exhibiting youth-like regulatory programs and unique features, including higher BDNF-related signatures.
- Authors described a potential neurogenesis-related resilience signature, noted key limitations and disputes over cell classification, and called for larger, longitudinal replication to identify upstream, potentially druggable cues; the study was funded by the National Institute on Aging.