November 23, 2004
First Methuselah Mouse Prize Awarded To Stephen Spindler

The Methuselah Foundation has awarded its first prize to a scientist for extending life-spans of middle aged mice. (same article here and here)

Dr. Aubrey de Grey, Chairman of The Methuselah Foundation (www.Mprize.org), awarded the first ever Methuselah Mouse Rejuvenation Prize to Dr. Stephen Spindler, who lead the first experiment to achieve rejuvenation in middle-aged mice, making them biologically younger while extending their lifespans.

The award was presented on November 21st during the 2004 Gerontological Society of America Conference in Washington, D.C.

Dr. Spindler's research was astounding because it began with mice that were in middle age. This research, first reported in Proceedings of the National Academy of Science achieved decisive increases of 15% average and maximum lifespan, AND was accompanied by significant early reductions of deaths from cancer. The fact that mice actually became younger was verified by genetic microarray analysis. Video showing that mice were more active and vibrant than their years can be found at http://www.biomarkerinc.com/html/video1-hi.htm

The Methuselah Foundation has attracted a number of notable donors and sponsors.

The Methuselah Foundation is supported by individuals who are no longer willing to stand by and do nothing while the diseases of aging disable and then take their irreplaceable loved ones away. They are taking matters into their own hands and inviting others to join with them to cure and reverse aging. Among the over 100 donors and sponsors, including the X PRIZE Foundation, Foresight Institute, the Life Extension Foundation, Dr. William Haseltine -- Founder of Human Genome Sciences and Dr. Raymond Kurzweil -- noted futurist and entrepreneur.

In addition to extending the lives of middle aged miced another one of Spindler's notable and useful achievements was showing that most of the gene expression changes caused by long term and life extending calorie restriction diets occur in mice which are first put on calorie restriction when they are elderly.

Finally, we investigated the effects of CR in mouse heart. Eight weeks of CR reproduced many of the long-term effects of CR on gene expression and physiology. CR rapidly decreased natriuretic peptide B and collagen I and III expression. CR reduced perivascular collagen accumulation and cardiomyocyte size in the left ventricle. These results suggest that hearts of LT-CR mice are physiologically younger than those of control mice. Switching CR mice to control feeding rapidly returned 91% of the CR responsive genes to control expression levels. Thus, CR rapidly and reversibly induced genomic changes associated with reduced cardiovascular pathology.

Importantly, these results suggest that it should be possible to use rapid treatments with pharmaceuticals and other compounds to identify agents that mimic the rapid changes in gene expression caused by caloric restriction. The gene expression biomarkers of caloric restriction can also be used to develop pharmaceuticals targeted to its genomic effects.

The usefulness of this result is that it can be used to more rapidly scan for drugs that act as calorie restriction (CR) mimetics which are capable of putting an organism's metabolism in the same state that is seen in animals or humans on calorie restricted diets. The calorie restriction extends average life expectancy. But consistently eating a small amount of calories every day is beyond the will power of most people and most people do not want the gaunt appearance seen in many CR practitioners. A drug that could induce the same metabolic state without requiring a constant fight against eating would appeal to a lot of people as a far easier way to extend their lives.

Spindler has co-founded a company named Biomarker Pharmaceuticals that is searching for calorie restriction mimetic drugs.

Recently, studies have shown that three dwarf mice mutations are capable of extending life span by approximately 40% through a molecular mechanism that may be different from that found in CR animals. These mutations also delay and ameliorate the effects of age-related diseases. BioMarker scientists--in collaboration with other scientists--are identifying the gene expression biomarkers associated with this model of life span extension.

Dr Stephen R. Spindler, scientific co-founder of BioMarker, studied longevity-related expression in 12,000 genes in mice using cDNA microarray chips. Gene expression data from these experiments indicate that even a brief period of caloric restriction produces about 70% of the changes associated with life span extension. These gene changes are correlated with a number of significant cellular changes including destruction of pre-cancerous cells (apoptosis), protection of cells from toxins and carcinogens, reduction in inflammation and improvements in cardiovascular health.

The bit about CR inducing pre-cancerous cells to die holds out the possibility that one could reduce one's risk of cancer by periodically going to a low calorie diet. Imagine doing a CR diet one month a year. One might kill off some pre-cancerous cells that otherwise would develop into a fatal cancer. It would be interesting to see whether periodic CR could increase average life expectancy of mouse strains by reducing the incidence of cancer. A CR mimetic drug holds out the possibility of doing the same thing.

Also see the Better Humans coverage of this story.

As the inaugural Rejuvenation Prize, Spindler's award sets the bar for other teams competing to reverse aging in mice, including the six teams already enrolled. To win, these teams must beat Spindler's record using groups of at least 20 mice that show rejuvenation in at least five different markers of aging.

Share |      Randall Parker, 2004 November 23 07:18 PM  Aging Reversal


Comments
Michael Vassar said at November 24, 2004 6:58 AM:

You said
"The bit about CR inducing pre-cancerous cells to die holds out the possibility that one could reduce one's risk of cancer by periodically going to a low calorie diet. Imagine doing a CR diet one month a year. One might kill off some pre-cancerous cells that otherwise would develop into a fatal cancer. It would be interesting to see whether periodic CR could increase average life expectancy of mouse strains by reducing the incidence of cancer. A CR mimetic drug holds out the possibility of doing the same thing."
I have been trying to get funding to attempt test exactly that for about a year, although I would be a bit more aggressive with the CR, pushing 1 month on, 2 months off, and testing both CR and 2 and 3 days per week of fasting against each other. You reach a lot of people Randal, why don't you see if you can find someone interested in doing this experiment?
Another experiment that would be worth attempting is the life-span effect of pregnancy in either mice that were kept on CR or mice which were removed from CR in order to carry to term.

Post a comment
Comments:
Name (not anon or anonymous):
Email Address:
URL:
Remember info?

                       
Go Read More Posts On FuturePundit
Site Traffic Info
The contents of this site are copyright