Brain aging consists of a progressive loss of functional capacities, which is associated with a progressive cognitive decline and can lead to neurodegenerative diseases. Studies comparing the underlying molecular mechanisms of the human hippocampus between young and older adults remain scarce. In our study, we completed a transcriptomic analysis from hippocampal samples of different ages and performed 2 complementary analyses. A comparison between young and old groups revealed a set of genes differentially expressed in aged individuals linked to inflammation and immune system pathways, DNA repair, metabolism, or neural activity. Correlation analysis showed that the expression of an additional subset of 6 genes was associated with chronological aging. Among them, further analysis identified RAD23B as the most significant gene with a negative correlation of its mRNA and protein expression with age in the human hippocampus. Its expression was even lower in patients with Alzheimer's disease. RAD23B was mostly expressed in neurons and astrocytes, where studies in human primary cultures uncovered that it is required for cell survival and function. In summary, these results unravel dynamic gene expression changes that distinguish young from older adults and identify RAD23B as a putative biomarker and regulator of cell aging in the brain.
Saenz‐Antoñanzas et al. (2026) studied this question.