The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 5 No.
6 • December 2002
IGF-1, and Alzheimer’s Disease
new paper in Nature Medicine
reports that serum IGF-1 regulates brain amyloid-beta levels. This is a hitherto
unreported effect of IGF-1, though it has been known that IGF-1 is required for
the neuroprotective effects of exercise on the brain and that it modulates adult
neurogenesis and increases neuronal excitability.
the authors note, insulin is known to modulate cellular clearance of
amyloid-beta, and IGF-1 protects neurons against amyloid-beta’s toxic effects.
In exploring the effect of IGF-1 on brain amyloid-beta levels, the researchers
used aged (over 18 months) rats that already had elevated levels of amyloid-beta
in the brain, and compared them to young rats. They found that IGF-1 treatment
caused amyloid-beta levels in the hippocampus and cortex of the aging rats to
decrease to those seen in young rats. Gliosis (the proliferation of brain glial
cells) seen with aging was “eradicated.”
researchers found that the transport of labeled albumin from the bloodstream
into the cerebrospinal fluid (CSF) was greatly enhanced with IGF-1 treatment.
Hence, they hypothesize that this might explain the increased amyloid-beta
clearance, since amyloid-beta might be transported out of the brain by albumin,
to which it is known to bind, or by other serum proteins.
other particularly interesting finding in this study is that TNF-alpha (tumor
necrosis factor-alpha, an inflammatory cytokine) antagonized the stimulatory
effects of IGF-1 on amyloid-beta clearance. This is just another good reason to
reduce fat stores. Fat cells (adipocytes) are known to synthesize and release
TNF-alpha into the circulation. Substances known to suppress TNF-alpha include
nonsteroidal anti-inflammatory drugs (NSAIDs), estrogen,
alpha-lipoic acid, resistance exercise, quercetin,
N-acetylcysteine, thalidomide, and pentoxifylline.
Carro et al. Serum insulin-like growth factor 1 regulates brain amyloid-beta
levels. Nature Med 8(12):1390-7 (2002).
- Joussen et al. Nonsteroidal anti-inflammatory drugs prevent early diabetic
retinopathy via TNF-alpha suppression. FASEB J (Jan. 30, 2002).
- Cenci et al. Estrogen deficiency induces bone loss by enhancing T-cell
production of TNF-alpha. J Clin Invest 106(10):1229-37 (2000). Walsh et
al. 17-beta-Estradiol reduces tumor necrosis factor-alpha-mediated LDL
accumulation in the artery wall. J Lipid Res 40:387-96 (1999).
- Zhang, Frei. Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation
and adhesion molecule expression in human aortic endothelial cells. FASEB J 15:2423-32
- Greiwe et al. Resistance exercise decreases skeletal muscle tumor necrosis
factor alpha in frail elderly humans. FASEB J 15:475-82 (2001).
- Wang, Mazza. Effects of anthocyanins and other phenolic compounds on the
production of tumor necrosis factor alpha in LPS/IFN-gamma-activated RAW 264.7
macrophages. J Agric Food Chem 50:4183-9 (2002).