A number of approaches to inducing muscle growth or improving muscle strength have been demonstrated in laboratory animals, in early human clinical trials, and in recent years employed in medical tourism clinics. These approaches are compensatory in the context of aging, they do not address any of the underlying issues that lead to loss of muscle mass and strength per se. An adjustment of the regulation of muscle growth to favor more growth will produce larger, stronger muscles at any age, which may help to generate greater attention and use of such therapies as they are developed.
These varied approaches directly interfere in cell signaling in some way, as it is easier to adjust the levels of circulating proteins and other molecules, or their ability to interact with cell surface receptors, then it is to adjust mechanisms that operate inside cells. Inhibition of myostatin signaling and upregulation of follistatin signaling are the presently dominant approaches. The use of antibodies targeting myostatin has been assessed, but more effort is now put toward upregulation of circulating follistatin via forms of gene therapy.
In today's open access paper, researchers discuss upregulation of a different signaling protein, FGF19. This does appear to have the effect of reducing myostatin levels, but that it only increases muscle strength rather than muscle mass suggests that other mechanisms are driving the outcome. Some indication has been given in recent years that these various strategies to grow muscle or improve muscle strength may also have a positive impact on bone mineral density. Unfortunately that doesn't seem to the be the case for FGF19.
Osteosarcopenia, characterized by the coexistence of osteopenia/osteoporosis and sarcopenia, represents a significant health concern in geriatrics, with an increased risk of falls and fractures. The enterokine fibroblast growth factor 19 (FGF19) was recently shown to prevent muscle weakness in preclinical models. This study investigated the therapeutic potential of FGF19 in mitigating bone and muscle deterioration in aged male mice. Twenty-one-month-old C57BL/6 male mice received daily injections of human recombinant FGF19 (0.1 mg/kg) for 21 days.
Histological and functional analyses revealed a shift toward larger muscle fibers in FGF19-treated mice as well as an increased muscle strength, without affecting muscle mass. In parallel, X-ray microtomography showed that FGF19 had no overt negative impact on bone, with a range of modest, site-specific, and opposing effects. In the distal femur metaphysis FGF19, it reduced cortical thickness, but significantly increased bone cross-sectional area, with an overall increased polar moment of inertia, a geometrical parameter linked to favorable mechanical properties. It also elevated cortical bone porosity in the same region. There were no significant effects on trabecular bone or cortical bone parameters in the proximal femur side. In the L2 vertebra, cortical porosity decreased. Histomorphometry of trabecular bone and analysis of transcriptional output of selected genes in femurs revealed only minor changes in bone cellular activities and gene expression after three weeks of treatment.
In conclusion, FGF19 treatment increased muscle strength in aged male mice, without negatively impacting aging bone.
View the full article at FightAging
