Life Extension Update
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Diabetes, obesity seen as accelerated aging
The July 2005 issue of the journal Nature Reviews Drug Discovery (http://www.nature.com/nrd) published a review by Rory Curtis, Bard J Geesaman and Peter DiSefano of Elixir Pharmaceuticals that documents the links between the aging process and metabolic disease. The authors suggest that as an alternative to targeting individual diseases that occur with aging, aging itself can be targeted to treat its associated conditions.
The authors show that the regulation of aging and energy homeostasis share molecular pathways. Many of the genes recently discovered that can be manipulated to slow the aging process belong to pathways involved in the control of metabolism. Energy homeostasis dysregulation occurs during the aging process, when aged men and women experience a reduced ratio of lean to fat mass, and a redistribution of fat from subcutaneous to visceral areas that surround the internal organs located in the body’s trunk. This leads to decreased insulin sensitivity and increased serum insulin, which can result in the metabolic syndrome and type 2 diabetes. Among younger individuals who have increased visceral fat mass there is a greater risk of the development of diabetes, heart disease, hypertension, gallbladder disease, neurodegenerative disease, and a number of cancers, all of which are associated with aging.
Degree of obesity has been found to be inversely correlated with life expectancy. Calorie restriction, which has been the most successful means so far to extend the lifespan of numerous species, prevents obesity and has been demonstrated to postpone many signs of aging and protect against a number of age-related diseases. This life extending therapy also has been shown to affect genes involved in energy metabolism. Calorie restriction, as well as genetically manipulating the insulin receptor in fat cells, prevents visceral obesity and its consequent insulin resistance and elevated insulin levels, in addition to extending lifespan.
The authors believe that this knowledge will aid in the development of drugs that could not only treat diabetes, obesity and other metabolic conditions, but slow the aging process itself and extend lifespan. Professor of Molecular Biology John Kopchick, PhD, of the Department of Biomedical Sciences, Konneker Research Center, Ohio University , commented, "The article by DiStefano et al. will stimulate a paradigm shift in our thinking about aging and age-related disorders. As pointed out by the authors, we are beginning to recognize that metabolic syndrome, in addition to being a precursor of serious diseases such as type 2 diabetes and cardiovascular disease, may be a sign of premature aging. For patients, this translates into the potential of a variety of novel drugs emerging from the science of aging, which then will be tested clinically in the treatment of metabolic diseases. What an exciting possibility!"
There are several hormones that impact how many ingested calories are stored as body fat. If any of these hormones are out of balance, a person can gain weight even though they may eat less food. One hormone that exerts a significant effect on hunger and fat storage is insulin.
Insulin is produced by beta cells in the pancreas mainly in response to high levels of glucose (sugar) in the blood. Insulin enables the liver to store excess serum glucose. Insulin also stimulates the liver to form fatty acids that are transported to adipose cells and stored as fat. The net effect of insulin is the storage of carbohydrate, protein, and fat in the body.
A poor diet can induce the pancreas to secrete large amounts of insulin. Aging people also experience metabolic disorders that cause the hypersecretion of insulin. Eventually the cells in the body become resistant to insulin (by decreasing the number of insulin receptors).
As cells become insulin resistant, the body stabilizes blood glucose by producing higher levels of insulin. The effect of high insulin production is weight gain. The long-term result is often Type II diabetes in which blood glucose levels become unstable even though insulin levels remain dangerously high.
As people accumulate excess body fat, they develop a chronic condition known as hyperinsulinemia, meaning the pancreas constantly secretes too much insulin and the body is unable to effectively utilize it.
According to the American Diabetes Association, more than 5 million of the 20 million Americans who have diabetes have not yet been diagnosed with the disease. A condition of elevated blood sugar, diabetes is the sixth leading cause of death in the United States. If current trends continue, diabetes and its complications will be America’s leading cause of death by 2010, surpassing both cancer and heart disease.
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