VCAM‐1 upregulation accompanies muscle remodeling following resistance‐type exercise in Snell dwarf (Pit1^dw/dw) mice

Abstract

Snell dwarf mice (Pit1dw/dw) exhibit deficiencies in growth hormone, prolactin, and thyroid stimulating hormone. Besides being an experimental model of hypopituitarism, these mice are long‐lived (>40% lifespan extension) and utilized as a model of slowed/delayed aging. Whether this longevity is accompanied by a compromised quality of life in terms of muscular performance has not yet been characterized. In this study, we investigated nontrained and trained muscles 1 month following a general validated resistance‐type exercise protocol in 3‐month‐old Snell dwarf mice and control littermates. Nontrained Snell dwarf gastrocnemius muscles exhibited a 1.3‐fold greater muscle mass to body weight ratio than control values although muscle quality, maximum isometric torque normalized to muscle mass, and fatigue recovery were compromised. For control mice, training increased isometric torque (17%) without altering muscle mass. For Snell dwarf mice, isometric torque was unaltered by training despite decreased muscle mass that rendered muscle mass to body weight ratio comparable to control values. Muscle quality and fatigue recovery improved twofold and threefold, respectively, for Snell dwarf mice. This accompanied a fourfold increase in levels of vascular cell adhesion molecule‐1 (VCAM‐1), a mediator of progenitor cell recruitment, and muscle remodeling in the form of increased number of central nuclei, additional muscle fibers per unit area, and altered fiber type distribution. These results reveal a trade‐off between muscle quality and longevity in the context of anterior pituitary hormone deficiency and that resistance‐type training can diminish this trade‐off by improving muscle quality concomitant with VCAM‐1 upregulation and muscle remodeling.

Circulating Vascular Cell Adhesion Molecule-1 (sVCAM-1) Is Associated With Left Atrial Remodeling in Long-Distance Runners

“…In the clinical context, there has been a ventricular level increase of VCAM-1 associated with hemodynamic stress in patients with rheumatoid arthritis ( 44 ) or intermittent claudication ( 47 ). In skeletal muscle tissue, an increase has been seen in post-prolonged exercise ( 48 ) associated with muscle remodeling ( 49 ).…”

Effect of the Rehabilitation Program, ReStOre, on Serum Biomarkers in a Randomized Control Trial of Esophagogastric Cancer Survivors

“…Interestingly, our 12-week exercise intervention did significantly alter the expression levels of soluble intracellular adhesion molecular (ICAM-1) and soluble vascular adhesion molecule (VCAM-1), members of the vascular injury panel at T1 compared to controls. Both soluble ICAM-1 and VCAM-1 are reported to be increased following exercise and circulating levels of cells are important in skeletal muscle remodeling (34)(35)(36). Similarly, we also found the exercise intervention group had elevated ICAM-1 and VCAM-1 at T1 compared to controls (Figure 1).…”

Improved impedance to maladaptation and enhanced VCAM-1 upregulation with resistance-type training in the long-lived Snell dwarf (Pit1dw/dw) mouse

“…Muscles were maximally activated for each SSC at ankle angle 90° for 100 ms, rotated to 70° at 60°/s, returned to 90° at 60°/s, and deactivated 100 ms later. SSCs at a velocity of 60°/s induce a response characterized by the absence of overt muscle inflammation and degeneration in rodents days to weeks into training [7,15,[39][40][41]. Isometric torque depression during and following the SSC session was assessed by comparing the torque for the isometric portion of the final SSC and the isometric torque 5 minutes following the SSCs, respectively, with pre SSCs maximal isometric torque.…”

“…Previous research demonstrated that muscles of this longevity animal model are weak and demonstrate poor performance maintenance during activity at young age. Specifically, 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, consequently, secondary deficiency in circulating insulin-like growth factor 1 (IGF-1)/insulin signaling [ 8 – 10 ].…”