Fig. 4. Muscle-derived Amyrel Preserves Protein Quality Control in the Brain and Retina during Aging.

Immunostaining of retinas and brains from 60-day-old flies for poly-ubiquitinated proteins (red), Ref(2)P/p62 (green), and F-actin (blue).

(A) Skeletal muscle-specific overexpression of Amyrel (Mhc>Amyrel) reduces the age-related accumulation of poly-ubiquitin protein aggregates in the brain and retinas of flies, compared to isogenic controls (Mhc>+).

(B-C) Similar results are found in response to drug-induced (+RU486) expression of Amyrel in thoracic flight skeletal muscle with Act88F-GS-Gal4, compared to uninduced controls and no transgene (+), in both the retina (B) and brain (C).

(D) Muscle-specific Prosβ1^RNAi systemically preserves protein quality control in the retina and brain during aging via Amyrel, as indicated by the higher levels of poly-ubiquitin protein aggregates found in the brains and retinas of flies with Prosβ1^RNAi+Amyrel^RNAi versus control Prosβ1^RNAi+yellow^RNAi. In (A-D), the scale bar is 20μm.

(A-D) Quantitation of the area of poly-ubiquitin protein aggregates in the brains and retinas of flies with muscle-specific modulation of Amyrel, Prosβ1^RNAi+Amyrel^RNAi, and controls. The n and SD is indicated.

In (A-D), higher (4x) magnification representative images are shown for each intervention.

(E) Proteasome stress in skeletal muscle improves protein quality control in the brain and retina during aging via the stress-induced myokine Amyrel.

Supplemental Fig. S3 reports additional data related to Fig. 4.