Abstract
Snell dwarf mice with the Pit1dw/dw mutation are deficient in growth hormone, prolactin, and thyroid stimulating hormone and exhibit >40% lifespan extension. This longevity is accompanied by compromised muscular performance. However, research regarding young (3-month-old) Snell dwarf mice demonstrate exceptional responsivity to resistance-type training especially in terms of a shifted fiber type distribution and increased protein levels of vascular cell adhesion molecule-1 (VCAM-1), a possible mediator of such remodeling. In the present study, we investigated whether this responsiveness persists at 12 months of age. Unlike 12-month-old control mice, age-matched Snell dwarf mice remained resistant to training-induced maladaptive decreases in performance and muscle mass. This was accompanied by retainment of the remodeling capacity in muscles of Snell dwarf mice to increase VCAM-1 protein levels and a shift in myosin heavy chain (MHC) isoform distribution with training. Even decreasing training frequency for control mice, an alteration which protected muscles from maladaptation at 12 months of age, did not result in the overt remodeling observed for Snell dwarf mice. The results demonstrate a distinct remodeling response to resistance-type exercise operative in the context of the Pit1dw/dw mutation of long-lived Snell dwarf mice.
Highlights
The Snell dwarf mouse with a recessive mutation in Pit1 (Pou1f1), an anterior pituitary transcriptional factor, results in combined anterior pituitary hormone deficiencies of growth hormone, thyrotropin, and prolactin has been an invaluable model to investigate lifespan extension [1]
Frequent 3 day per week training initiated an agedependent decline in muscle mass, maximal performance, and muscle quality for control mice while no such training-induced decrement was observed for 12-month-old Snell dwarf mice
This response in Snell dwarf mice was accompanied by remodeling in vascular cell adhesion molecule-1 (VCAM-1) protein levels and muscle fiber myosin heavy chain (MHC) isoform distribution thereby indicating these responses as possibly compensatory when anterior pituitary hormones are deficient
Summary
The Snell dwarf mouse with a recessive mutation in Pit (Pou1f1), an anterior pituitary transcriptional factor, results in combined anterior pituitary hormone deficiencies of growth hormone, thyrotropin, and prolactin has been an invaluable model to investigate lifespan extension [1]. At 3 months of age for Snell dwarf mice, muscle quality (force normalized to muscle mass) was low and the capacity for isometric torque to be sustained in the minutes following contractions was especially compromised at values 20% of those for control littermates [7]. This outcome was not unexpected given the deficiency in growth hormone and, secondary deficiency in circulating www.aging‐us.com insulin-like growth factor 1 (IGF-1)/insulin signaling [8,9,10]. While this research provided insight in characterizing the responsiveness at young age in the presence of the Pit mutation, whether this remodeling signature persists was not tested
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