Meet the Competitors

Competitor Andrzej Bartke

We are working with mutant mice in which reduced release of several hormones from the pituitary or resistance to the actions of one of these hormones are associated with very impressive (approximately 50%) increase in life expectancy. These animals not only live long but are also partially protected from cancer and other age-related diseases and maintain their memory and learning ability into very late life. Our research, together with the findings from other laboratories, suggests that improved responses to insulin may explain the envious characteristics of these mutant mice. We strongly suspect that altered action of insulin in a particular organ or cell type is responsible for the delay of aging in these mice and that these alterations at a particular stage of life may be especially important. Our aim is to find how, where and when must the action of insulin be altered to produce a long-lived individual.

Few people not directly involved in gerontological research are fully aware of the exciting developments in the study of aging and what I feel is the very real prospect of devising effective means of postponing age-related disease and functional decline and yes, prolonging life. The Methuselah Mouse Prize captures popular attention, as evidenced by extensive media coverage it already received, and I believe will play a very important role in securing continued public interest in the work on mechanisms and control of aging.

Competitor Alan Cash

The focus of Mr. Cash's research and development at Terra Biological LLC is on small molecules that simulate the genomic effects of caloric restriction ("caloric restriction mimics" or "CR mimetics"). CR mimetics have been shown to increase the lifespan of laboratory test animals, namely C. Elegans worms, D. Melanogater flies and, in a small pilot test, M. Musculus mice by up to 36%.

Mr. Cash is an entrepreneur with formal training in physics and geology, who has studied the biological and biochemical aspects of aging research with scientists in the field. He is working with the National Institutes of Aging Division of the US National Institutes of Health and also investing his own funds in this research. The NIA/NIH is currently evaluating the inclusion of one of Terra Biological's CR mimetics in its ITP test program in mice to measure its biological effects on life and health span. These larger scale mouse tests will constitute the entry into the Mprize competition.

Mr. Cash commented, "My hopes in entering the Mprize competition are to demonstrate and confirm, on a larger scale in mice, the effectiveness of specific small molecule, biochemical control of aging. This biochemical control, which has already been shown to simulate calorie restriction - CR, a scientifically tested and accepted method of increasing life and health span - will be tested beginning with middle aged mice, about 16 months old."

Competitor Craig Cooney

I am working on a paper right now for a study I just completed in competition for the MPrize. I am also doing grant applications for new studies; it takes many years. If I have a new idea today for a breakthrough in mouse lifespan, the results could easily be 10 years off.

My work involves epigenetics, changes in appearance or gene expression that do not change the underlying DNA. We hope to find ways to maintain cells for decades, avoiding the breakdown that we see now in aging. This dysfunction may cause skin or liver cells to stop doing their job and, just like a very elderly person, they are unable to contribute. We need to understand these mechanisms and combine different approaches - genetics, diet, drugs - to begin to see real changes in longevity and long term health.

Methuselah Foundation is a great connector; one of the cool things about it is that it is not competing. The goal is to get more people involved in research on aging. If five other groups offered prizes, Methuselah would still have achieved its goal.

Competitor Leonard Guarente

Why do living things age? What genes influence longevity? Is it possible to extend youthfulness by means of genetic manipulation? Our research analyzes these tantalizing questions and others in molecular detail.

The mammalian ortholog Sirt1 has several functions that trigger physiological changes seen during CR. First, Sirt1 makes cells more resistant to oxidative or radiation-induced stress, which is a phenotype of rodent cells from CR animals. Second, Sirt1 promotes mobilization of fat from white adipose tissues, a change triggered by CR that is sufficient to extend the life span. It does this by modulating the activity of the key regulator of white fat, PPARg. Third, Sirt1 mediates the metabolism of energy sources in metabolically active tissues. CR animals are efficient in metabolism rendering them insulin-sensitive. Fourth, Sirt1 regulates the induction of insulin in pancreatic beta cells, an obvious component of energy utilization during CR. In several cases, Sirt1 is activated by starvation or stress to carry out these functions. Molecular mechanisms of Sirt1 activation and its functions in triggering the physiological changes elicited by CR are under study.

There are six other mammalian SIR2-related genes besides Sirt1. Functional studies of Sirt2, 3, 4, and 7 are being carried out. At least some of them also appear to play a role in CR. Sirt2 appears to regulate insulin sensitivity in mice. Recent findings also show a possible link between Sirt2 and cancer. Sirt4, like Sirt1, plays a role in regulating insulin production in beta cells. This regulation is mediated from the mitochondria, the cellular compartment where Sirt4 resides.

Competitor Tom Johnson

I always knew I wanted to be a scientist. I remember seeing Our Friend the Atom, a Disney TV movie, when I was 7 or 8. What stuck in my mind was the nuclear genie that was let out of the bottle and couldn't be put back in.

Now I'm entering the competition for the MPrize with a study to identify longevity genes in mammals. Interestingly, no mammalian genes have ever been identified that weren't first identified in other species. By working with a large population of genetically diverse mice, my team plans to identify variants and isolate the genes that contribute to a longer life.

Knowing the gene makeup of the mice will allow us to "build" a mouse with a greater lifespan. These genetically altered mice will live with environmental conditions and dietary restrictions that have already proven conducive to longer life.

As you can see from my video, I am a pioneer in the science of aging. Although other people have often claimed the credit for discovering mutants that extend life span, it was Mike Klass and I who were the first to do this. There is still a lot of work to help the public get past the acceptance of the inevitability of aging and discover that longevity can be manipulated, health can be modulated.

Competitor Christiaan Leeuwenburgh

Our general research interest is in the area of free radical biology and aging. Aging and several diseases including cardiovascular disease, diabetes, and neurodegenerative diseases are thought to result from increased formations of reactive oxygen species and reactive nitrogen species (aka, free radicals) resulting in oxidative stress. Reactive oxygen species are highly reactive molecules that cause damage to plasma membranes, enzymes, glucose molecules, and DNA. We are particularly interested in the oxidative mechanisms of aging and the effects of these during the aging process (i.e. mitochondrial dysfunction, apoptosis).

Mitochondiral oxidative stress with aging may be liked to apoptosis. Apoptosis is a highly regulated form of cell death characterized by specific morphological, biochemical, and molecular events. However, its role during aging, particularly in post mitotic tissues such as the brain, heart and skeletal muscle has not been studied in depth. Apoptosis appear to increase in post-mitotic tissues with age and it may be a major contributing factor to the observed loss in tissue function with age. The mechanisms by which apoptosis are induced with advancing age and adaptations that may protect against apoptosis remain to be identified, however. Moreover, the adaptations of major regulatory proteins upon the activation of the apoptotic signal transduction pathways during normal aging are unknown. Caloric restriction - an intervention that reduces oxidant production, improves calcium handling, reduces cell loss and extends maximum life span - could be emplyed to further study the anti-apoptotic adaptations. In addition, skeletal and heart muscle function with age could relate to apoptosis and apoptosis may be attenuated by caloric restriction. Further research would allow us to understand the mechanisms of apoptosis in vivo with normal aging, and caloric restriction.

Competitor Jennifer Lemon

According to a recent study by Jennifer Lemon, key factors implicated in aging include reactive oxygen species, inflammatory processes, insulin resistance, and mitochondrial dysfunction. All are exaggerated in transgenic growth hormone mice (TGM), which display a syndrome resembling accelerated aging. We formulated a complex dietary supplement containing 31 ingredients known to ameliorate all of the above features. We previously showed that this supplement completely abolished the severe age-related cognitive decline expressed by untreated TGM, and went on to demonstrate that longevity of both TGM and normal mice is extended by this supplement.

Treated TGM showed a 28% increase (p < .00008) in mean longevity. An 11% increase in mean longevity was also significant (p < .002093) for treated normal mice, compared to untreated normal mice. These data support the hypothesis that TGM are a model of accelerated aging, and demonstrate that complex dietary supplements may be effective in ameliorating aging or age-related pathologies where simpler formulations have generally failed.

Read more »

Competitor Michal Masternak

My work expands on the work of Andrzej Bartke, the previous MPrize winner. The long life of his mouse resulted from "knocking out" the growth hormone receptor. We recognize that several types of dwarf mice have a longer lifespan than other mice. Our team will combine these two factors and breed mice lacking both growth hormone and growth hormone receptor.

We are breeding 80 extremely small mice, we expect them to be exceptionally long-lived but otherwise they are normal. Other groups of mice will be used to study insulin/glucose function to be able to correlate these changes with longevity outcome. A lack of insulin and/or trouble responding to insulin is a common health threat to overweight people. Additionally, people become insulin resistant and glucose intolerant as they age.

We are discovering as we go with the hope of creating a model to start the search for the genes that indicate a long, healthy life. We expect to be able to isolate the genes and make alterations without changing the whole phenotype.

Competitor Elise Sacane

Mrs. Elise Sacane, co-founder of Neural Learning Systems of Tucson, Arizona and a retired science teacher is currently competing for the Mprize. Neural Learning Systems is a partnership established by Mrs. Sacane and her husband, corporate executive Louis "Jim" Sacane. The focus of Mrs. Sacane's research and development will be on the evaluation of the synergistic effects of fresh food diets, enriched housing and exposure to microbes on the behavioral aspects, life and health spans of wild type mice (Mus musculus).

Because her husband works in the aerospace industry, the Sacanes are familiar with the X PRIZE, after which the Mprize is modeled. Jim remarked, "What is exciting about being part of the Methuselah Foundation's endeavors is that the Mprize is a catalyst for personal innovation and inspiration and these are the true fundamental elements of great discoveries."

Elise commented, "My hopes in entering the Mprize competition are to demonstrate several important factors which will complement healthy mice behavior, deliver a variety of important, synergistic nutrients to them and favorably affect their life and health spans. The Mprize certainly presents one of the most exciting quests of our time."

Competitor Christian Sell

A decline in tissue function and protein synthesis occurs with increasing age. This catabolic state is associated with a decrease in the serum levels of IGF-I and IGF-I supplementation has been proposed as a therapy for elderly individuals. Not only is there a decline in the levels of IGF-I in the serum but the response of cells to IGF-I decreases with increasing age.

In vitro, human cells that have reached the end of their lifespan do not proliferate in response to IGF-I or other growth factors that will induce proliferation in the cells early in their lifespan. The reason for this lack of response is not clear and may be tied to fundamental changes within the cell that are important to the loss of function seen in "old" cells. For example, the rate of protein synthesis is regulated in part by IGF-I and, as mentioned above, protein synthesis declines with age both in the body and in vitro. An understanding of the changes in IGF-I responses are regulated and their connection to the senescent growth arrest may provide novel therapeutic approaches to some of the problems associated with aging.

Competitor David Sinclair

My work focuses on preventing and treating major diseases by manipulating genes that control how fast we age. Ignoring the conventional wisdom that the aging process is too complex to find drugs that could slow it, we are working to uncover single genes that could dramatically extend the lifespan of laboratory organisms such as yeast, worms, flies and mice.

Calorie Restriction (CR) is currently the only treatment that is proven to prevent all diseases of aging including cancer, heart disease, osteoporosis, diabetes and neurodegeneration. Recent studies in our lab and others indicate that the health benefits of CR are mediated by the Sirtuins, a recently discovered family of seven enzymes that control functions including metabolism, cell survival, and organ degeneration.

Animals lacking Sirtuin genes do not respond to CR while additional gene copies extend lifespan. Based on these findings, we have engineered small molecules that can activate mammalian Sirtuins in vivo, with a view to developing drugs that can treat the diseases of aging and promote cell survival and recovery following an injury.

Sirtris, the company I co-founded to explore sirtuin research, now owned by GlaxoSmithKline, is conducting clinical trials to test potent SIRT1 activators in a variety of diseases of aging including type II diabetes.

Competitor Stephen Spindler

The rate of animal aging is strongly influenced by diet. The more calories consumed, the faster it ages. Well-fed animals not only age faster, they have higher mortality from cancer, heart disease, and diabetes. And the reverse is true, the fewer calories eaten (provided malnutrition is avoided) the slower an animal ages, the lower the death rate from cancer, and the lower the rate of heart disease and diabetes. CR has been viewed as less effective in older animals and as acting incrementally to slow or prevent age-related changes in gene expression. However, we found that mice who begin CR in late middle-age reap its benefits almost immediately.

We also have performed other genome-wide gene-expression studies in mice with disrupted growth hormone-insulin-like growth factor-1 signaling (DF) that were either CR or given free access to food. Others have shown that either DF or CR alone can extend lifespan, and that together they act additively to extend the lifespan of mice even more. We found that CR and DF additively affected the expression of a group of genes. Individually and together, DF and CR independently affected the expression of other groups of genes. These results indicate that DF and CR affect overlapping sets of genes, and additively affect a subset of genes associated with enhanced longevity. These results provide a focused group of new genes which are important in regulating the lifespan of mammals, and which may be 'drugable targets' for anti-aging therapeutics.

Competitor Richard Weindruch

Our latest work with Calorie Restriction and monkeys has captured headlines. It's a long time coming. When I started as a graduate student at UCLA there were only 15 - 20 labs across the country working in the field, only a couple of those with CR. Now there are hundreds, many working with CR.

We have found that the monkeys on a regular diet are three times more likely to get cancer, heart disease or diabetes. These are the illnesses that rob people of a long, healthy life. We also looked at atrophy of the brain and sacropenia, the loss of muscle mass associated with aging. If CR causes monkeys to live stronger and healthier than quality of life improves, not just quantity.

Eight years ago Tom Prolla and I started LifeGen Technologies using our patented technology to screen for nutrients based on gene activity. Over the last decade we have tried to discover the genes associated with aging by using DNA microarrays to compare the activity of thousands of genes in young and aged animals. The same approach is used to study how the aging process is retarded by CR.

I eat carefully but do not strictly follow CR.

Competitor Bruce Teter

In the study by Stephen Spindler at UC Riverside, testing two doses of curcumin in the Longvida formulation, the mice are still surviving at about 80%, so it is too early to tell compared to untreated mice, and although calorie restricted (CR) mice are 90-95% surviving at this age, it is too early to tell if curcumin is different than CR. It will be several months before enough mice have died (usually at the point of 50% mortality in untreated, control mice). For the NIA ITP study of pure curcumin, it will be about 2 months before 50% mortality in the control mice, at which point the analysis of median life span extension will be made.

Also, I am organizing clinical trials of curcumin in the bioavailable Longvida formulation for treating age related diseases. The Longvida formulation recently became commercially available.

I became interested in curcumin, the molecule of the spice turmeric that gives it its color, through my contribution to the development of curcumin as a therapeutic drug for Alzheimer's disease. My interest in longevity developed through my work on the gene apolipoprotein E, which modulates the age of onset of Alzheimer's disease and affects human longevity.

While two published studies have shown longevity effects of curcuminoids in rodents, there is no evidence that humans who consume a diet high in curcumin, or its source turmeric, live longer because of the curcumin; the amount of curcumin in turmeric is low compared to the amount of curcumin used to show its longevity effects in rodents. You would have to eat a lot of turmeric to get enough curcumin. There is the possibility that lifelong consumption of turmeric-rich foods prepared in the right way would cumulatively have a longevity effect. Curcumin has shown effects similar to Calorie Restriction, including anti-inflammation, antioxidant and anti-carcinogen.

Test are being done at Stephen Spindler's University of California, Riverside lab and at three other labs through the Interventions Testing Program (ITP) of the National Institute on Aging (NIA).