Clinical implications of the reduced activity of the GH-IGF-I axis in older men.
During the last decade, a significant body of evidence has accumulated, indicating that IGF-I might play a role in several pathological conditions commonly seen during aging, such as atherosclerosis and cardiovascular disease (CVD), cognitive decline, dementia, sarcopenia and frailty. A vascular protective role for IGF-I has been suggested because of its ability to stimulate nitric oxide production from endothelial and vascular smooth muscle cells. In cross sectional studies, low IGF-I levels have been associated with unfavorable CVD risk factors profile, such as atherosclerosis, abnormal lipoprotein levels and hypertension, while in prospective studies, lower IGF-I levels predict future development of ischemic heart disease. The fall in IGF-I levels with aging correlates with cognitive decline and it has been suggested that IGF-I plays a role in the development of dementia. IGF-I is highly expressed within the brain and is essential for normal brain development. IGF-I has anti-apoptotic and neuroprotective effects and promotes projection neuron growth, dendritic arborization and synaptogenesis. Collectively, these data are consistent with a causal link between the age-related decline in GH and IGF-I levels and cognitive deficits in older persons. Finally, there is evidence of a relationship between declining GH and IGF-I levels and age-related changes in body composition and physical function. However, few studies have documented a precise role of IGF-I in the development of sarcopenia, frailty and poor mobility. We have recently documented that serum IGF-I is significantly associated with measures of muscle strength and physical performance in men and to a lesser extent in women. In conclusion, IGF-I is a pleiotropic hormone that in older persons may positively affect the cardiovascular system, the central nervous system and physical function.
Ceda
G P
GP
Department of Internal Medicine and Biomedical Sciences, Section of Geriatrics, University of Parma, 43100 Parma, Italy. gpceda@unipr.it
Dall'Aglio
E
E
Maggio
M
M
Lauretani
F
F
Bandinelli
S
S
Falzoi
C
C
Grimaldi
W
W
Ceresini
G
G
Corradi
F
F
Ferrucci
L
L
Valenti
G
G
Hoffman
A R
AR
D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000209:etiology; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008569:Memory Disorders; D009043:Motor Activity / Q000502:physiology
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone