Reductions in serum IGF-1 during aging impair health span

Area of Science:

• Endocrinology
• Aging Research
• Molecular Biology

Background:

• Insulin-like growth factor-1 (IGF-1) and insulin signaling pathways influence lifespan in simpler organisms.
• In rodents, growth hormone (GH) regulates IGF-1 and impacts lifespan, but congenital disruptions complicate age-related effects.
• Human IGF-1 levels peak in puberty and decline with age, unlike in rodents.

Purpose of the Study:

• To investigate the age-related effects of GH/IGF-1 signaling on health span.
• To develop a model that allows temporal control of IGF-1 levels in adult animals.

Main Methods:

• Development of an inducible liver IGF-1-deficient (iLID) mouse model.
• Temporal deletion of the liver Igf-1 gene at one year of age.
• Analysis of serum IGF-1, GH levels, STAT5B phosphorylation, liver pathology, oxidative stress, and skeletal integrity.

Main Results:

• Liver-specific IGF-1 deletion reduced serum IGF-1 by 70% in one-year-old mice.
• Reduced IGF-1 led to increased GH, liver weight, inflammation, oxidative stress, and hepatic tumors.
• Low IGF-1 compromised skeletal integrity and accelerated bone loss, despite elevated GH.

Conclusions:

• An intact GH/IGF-1 axis is crucial for maintaining health span.
• Elevated GH, particularly in the context of low IGF-1 late in life, is associated with increased pathology and accelerated aging.