Session: FP22-Testis Biology
Room 104 (Moscone Center)
Poster Board SUN-536
Experimental Design: To test this hypothesis, we established the following heterochronic parabioses between Y and O C57BL6 male mice of 4 and 22 months of age, respectively: 1) Y:O; 2) castrated Y:O; and 3) Castrated + testosterone-treated Y:O. A group of young and old mice received empty implants and were used as controls. Parabiotic pairings were maintained for 4 weeks prior to analysis.
Results: Serum testosterone levels were 3-fold higher in young in comparison with old mice. Compared with heterochronic parabioses with castrated young, old mice paired with testosterone-treated orchiectomized young partners had significantly elevated levels of serum testosterone. Heterochronic parabiosis to castrated young partners exhibited perturbed muscle ultrastructure, including intramyofibrillar lipid accumulation, mitochondrial swelling with broken cristae, vacuolated mitochondria, and tubular aggregation similar to aged muscles. Notably, parabiosis with castrated + testosterone-treated young mice but not with castrated young partners fully reversed the age-related changes in gastrocnemius muscle weight, muscle ultrastructure, muscle fiber cross-sectional area, and restored Notch signaling to levels seen in young controls.
Conclusions: Together, these novel findings point to a critical role of testosterone in restoring the systemic environment that favors muscle growth in aging. Undoubtedly, the identification of the testosterone-mediated rejuvenating factors in the aged niche may reveal novel therapeutic avenues for regenerative medicine using cellular-, stem cell-, and drug-based approaches.
Nothing to Disclose: IS, IS, RG, RS, AJW, APS
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