Brain-wide reductions in cell size and volume emerge early during adulthood in Drosophila melanogaster
Year: 2025
Type: preprint
Abstract: Aging is accompanied by complex cellular changes in the brain, yet alterations in cell size and brain volume during early adulthood remain poorly characterized. We used flow cytometry to examine cell size in the aging Drosophila melanogaster brain across genotypes, sexes, and brain regions, comparing the optic lobes (OL) and central brain (CB). We found substantial heterogeneity in brain cell sizes accompanied by a significant decrease in average cell sizes with age across genotypes, sexes, and regions. This reduction emerged early in adulthood and occurred in both the OL and CB, although the OL contained smaller cells than the CB. In parallel, we detected significant age-dependent accumulation of polyploid cells, defined as cells with a greater than 2C DNA content. Although polyploid cells were larger than diploid cells, they also exhibited an age-associated decline in average size. Adult-specific neuronal overexpression of Myc blunted the age-associated reduction in average cell size, indicating that this phenotype is modifiable by a known cell growth regulator. To determine whether cellular changes were accompanied by tissue-level alterations, we used micro-computed tomography to assess brain volume during early adulthood. In w 1118 flies, brain volume decreased with age regardless of sex, consistent with the decrease we observe in average brain cell size. Together, these findings identify early brain-wide changes in cell size and volume during early adulthood in Drosophila melanogaster as prominent features of early brain aging and provide a foundation for investigating age-dependent cellular remodeling and its underlying mechanisms and functional consequences. Article Summary Changes in cell size and tissue structure occur in the brain with age. This study examined these changes during early adulthood in Drosophila melanogaster . The authors measured cell size, DNA content, and volume across sexes, genetic backgrounds, and brain regions. Notably, average brain cell size decreases and brain volume is significantly reduced as early as seven days of age in the adult fly. Increasing Myc expression, a growth-regulating protein, specifically in adult neurons slowed the aging-associated cell-size decline. These findings establish that cellular and tissue-level reductions similar to brain atrophy occur early during aging in Drosophila .
Institutions: University of Michigan, University of Wyoming
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4415203206