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Nutrient Sensing and the Metabolic Syndrome of Aging
American Federation for Medical Research
Nir Barzilai
Dr. Luciano Rossetti., Dr. Michael Brownlee, Dr. Meredith Hawkins. Dr.
Nir Barzilai
The ‘metabolic syndrome of aging’ in this
program refers to a constellation of metabolic defects including insulin
resistance, abdominal obesity, dyslipidemia, hypertension and increased
circulating levels of pro-thrombotic and pro-inflammatory peptides. This
syndrome is an important risk factor for cardiovascular disease and other
age-related diseases, with significant impact on all-cause mortality. We
hypothesize that aging is characterized by a decline in hypothalamic
function leading to a relative or absolute increase in energy intake,
increased fat mass and impaired regulation of fat distribution. We propose
that the resulting increases in nutrient availability, total adiposity and
abdominal fat distribution contribute both independently and cooperatively
to the metabolic syndrome of aging. The hexosamine biosynthetic pathway (HBP)
may provide a unifying role as a ‘nutrient-sensing’ pathway, since its
activation by nutrient excess results in functional alterations of key
intracellular proteins by glycosylation. Activation of the HBP in fat and
endothelial cells induces the expression of pro-thrombotic and
pro-inflammatory peptides, which may contribute to insulin resistance and
endothelial dysfunction. Increased fat mass, and selective increases in the
metabolically dangerous abdominal fat, would therefore potentiate the above
process. The goals of this symposium are: To demonstrate that excess
nutrients can initiate the key components of the metabolic syndrome of
aging.; To implicate specific nutrient-sensing pathways in the
pathophysiolgy of this syndrome; and to discuss new therapeutic approaches
for the protection from age-related diseases. These lectures will be given
by a team of investigators at the Albert Einstein College of Medicine. This
symposium will spans the full spectrum from cell biology to in vivo animal
physiology to ‘translational’ studies in humans.
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