Protein Restriction Slows Progression of Mouse Model of Alzheimer's Disease

Calorie restriction slows the progression of near all measurable aspects of degenerative aging, and improves near all measures of health. It extends life by up to 40% in mice, and one of the interesting challenges for the study of metabolism is to explain the mechanics of how it can improve health so greatly in humans while failing to extend life to the same degree as it does in shorter-lived mammals. There is a good evolutionary explanation for this phenomenon; the expected length of a naturally occurring famine is the same whether you are a mouse or a man, and thus life span changes in response to famine must be more dramatic in a shorter lived species in order to have a decent chance of surviving it to reproduce. But that doesn't tell us how it happens under the hood.

Some of the triggers for the metabolic changes of calorie restriction involve sensing protein levels. Maintaining the same calorie intake while reducing dietary protein levels captures some fraction of the full effects of calorie restriction, with methionine seemingly the most important triggering protein.

Here a noted calorie restriction researcher shows protein restriction to slow the progression of a mouse model of Alzheimer's disease - which is pretty much the expected result, given what we know so far of how the effects of protein restriction map to those of calorie restriction:

Low-protein diet slows Alzheimer's in mice

Mice with many of the pathologies of Alzheimer's Disease showed fewer signs of the disease when given a protein-restricted diet supplemented with specific amino acids every other week for four months. Mice at advanced stages of the disease were put on the new diet. They showed improved cognitive abilities over their non-dieting peers when their memory was tested using mazes. In addition, fewer of their neurons contained abnormal levels of a damaged protein, called "tau," which accumulates in the brains of Alzheimer's patients.

Upcoming studies [will] attempt to determine whether humans respond similarly - while simultaneously examining the effects of dietary restrictions on cancer, diabetes and cardiac disease. "We had previously shown that humans deficient in Growth Hormone receptor and IGF-I displayed reduced incidence of cancer and diabetes. Although the new study is in mice, it raises the possibility that low protein intake and low IGF-I may also protect from age-dependent neurodegeneration."

The team found that a protein-restricted diet reduced levels of IGF-1 circulating through the body by 30 to 70 percent, and caused an eight-fold increase in a protein that blocks IGF-1's effects by binding to it. IGF-1 helps the body grow during youth but is also associated with several diseases later in life in both mice and humans. Exploring dietary solutions to those diseases as opposed to generating pharmaceuticals to manipulate IGF-1 directly allows [researchers] to make strides that could help sufferers today or in the next few years.

"We always try to do things for people who have the problem now. Developing a drug can take 15 years of trials and a billion dollars. Although only clinical trials can determine whether the protein-restricted diet is effective and safe in humans with cognitive impairment, a doctor could read this study today and, if his or her patient did not have any other viable options, could consider introducing the protein restriction cycles in the treatment - understanding that effective interventions in mice may not translate into effective human therapies."

You might take note of those last remarks as indicative of one of the ways in which regulation steers researchers towards deliberately aiming to produce marginal benefits rather than revolutionary advances - slowing the pace of progress and shutting down promising avenues of medical science before they even get started.

Comments

I wonder if this has anything to do with autophagy. When starved for protein, the body may begin scavenging cells for junk proteins to recycle, resulting in autophagic clearance of tau proteins. The abstract says that there was no reduction in amyloid beta, unfortunately.

Posted by: Brandon Berg at February 15th, 2013 11:02 PM

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