Glial DIP-β extended the lifespan of fruit flies in an aging brain screen
Increasing DIP-β in support cells in the adult fruit fly brain extended lifespan using two genetic approaches
On August 4, eLife published a study of DIP-β, a protein found on the surface of glia, the cells that support neuronal function. The authors compared proteins on the glial surface in the brains of five- and 50-day-old flies, found that DIP-β declined with age, and increased its production after the nervous system had developed. Both males and females with increased protein production lived longer than control flies.
“Aging is often described as a process within cells: DNA becomes damaged, mitochondria function less effectively, and proteins misfold. However, aging also changes how cells communicate with one another,” write Michael Pokrass and Nan Hao in an eLife commentary.
Glia supply neurons with nutrients and contribute to waste removal and local repair. Proteins on the glial surface help cells recognize their neighbors and exchange signals. The authors looked for age-related changes among these surface proteins. They equipped the glial surface with an enzyme that labeled nearby proteins within minutes, then compared the labels in young and old flies. After filtering, the analysis included 872 surface proteins. DIP-β levels declined with age.
DIP-β belongs to a family of cell recognition proteins. During nervous system development, these proteins help cells find suitable partners and assemble neural circuits. The authors tested 19 genes whose protein products became less abundant on the glial surface with age. Using available genetic lines, they activated these genes in adult flies. This design allowed them to examine the relationship between DIP-β and aging separately from its role in building the nervous system. DIP-β was the only candidate that extended lifespan in both males and females. The result was reproduced using two different methods to increase gene activity.
The researchers then analyzed RNA from 48 959 cell nuclei obtained from two pooled samples of heads from 50-day-old females. DIP-β was increased in one sample, while the other served as the control. The largest changes in gene activity occurred in the fat body, a tissue that stores nutrients and contributes to metabolism, and in glia. A computational analysis matched known pairs of signaling molecules and receptors across cell types. When DIP-β was activated, expression increased in 61% of the ligands and receptors that changed. The predicted signals included communication between glia and neurons and between glia and the fat body.
The study brought together three observations in fruit flies. DIP-β on the glial surface declined with age. Activating it in adult animals extended lifespan. RNA analysis identified cells and signaling pairs for further testing. A protein known for its role in assembling neural circuits has therefore become a candidate for investigating how contacts between cells change in the aging brain.