The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis.
The widespread increase in life expectancy is accompanied by an increased prevalence of features of physical frailty. Signs and symptoms may include sarcopenia and osteopenia, reduced exercise capacity, and diminished sense of well-being. The pathogenesis of age-associated sarcopenia and osteopenia is multifactorial, and hormonal decline may be a contributing factor. Aging is associated with a progressive decrease in GH secretion, and more than 30% of elderly people have circulating IGF1 levels below the normal range found in the young. GH acts directly on target tissues, including skeletal muscle and bone among many others, but many effects are mediated indirectly by circulating (liver-derived) or locally produced IGF1. Aging is also associated with reduced insulin sensitivity which, in turn, may contribute to the impairment of IGF1 action. Recent experimental evidence suggests that besides the age-dependent decline in GH and IGF1 serum levels, the dysregulation of GH and IGF1 actions due to impairment of the post-receptor signaling machinery may contribute to the loss of muscle mass and osteopenia. This article will focus on the molecular mechanisms of impaired GH and IGF1 signaling and action in aging, and their role in the pathogenesis of sarcopenia and osteoporosis.
Perrini
Sebastio
S
Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari School of Medicine, Piazza Giulio Cesare, 11, I-70124 Bari, Italy.
Laviola
Luigi
L
Carreira
Marcos C
MC
Cignarelli
Angelo
A
Natalicchio
Annalisa
A
Giorgino
Francesco
F
D000818:Animals; D001842:Bone and Bones / Q000503:physiopathology; D004195:Disease Models, Animal; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D018482:Muscle, Skeletal / Q000503:physiopathology; D010024:Osteoporosis / Q000503:physiopathology*; D055948:Sarcopenia / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone