Research Overview: Aging-Intervention Technologies

BioMarker's proprietary technologies are based on identifying genes and proteins involved in aging and age-related diseases. By comparing differences in expression in animals and humans with changes in gene and protein expression in models in which aging has been slowed, BioMarker is pinpointing targets for the development of new anti-aging and anti-disease therapies. Although we use a suite of expression analysis technologies, much of our research focus is on our proprietary system for the development of products that mimic the effects of calorie restriction (CR) – to date, the only intervention known to consistently extend lifespan and retard aging in mammals.

An Introduction to CR The history of caloric restriction research dates back to the 1910's. Francis Peyton Rous showed that reducing food intake inhibited tumors in rodents. The ability of CR to retard aging and extend maximum lifespan in mammals was first clearly addressed by Dr. Clive McCay, a nutritionist at Cornell University in 1930's. He reported that CR rats lived for 48 months, while his control-fed animal died at 30 months of age. Later studies by Dr. Morris Ross at the Institute For Cancer Research in Philadelphia, showed that CR rats stayed alive for 59 months. Since then, the effects of CR have been reproduced in many laboratories around the world. CR studies in rats and mice have now shown that a 30-50% reduction in calories produces a 30-80% increase in longevity. When all nutrients are maintained at levels sufficient for health, while total calories are reduced, animals remain active and less vulnerable to cancer and cardiovascular disease with advancing age than animals on an unrestricted diet. The National Institute on Aging has also carried out caloric restriction studies in monkeys. Their experiments with rhesus monkeys show a trend towards delaying age-related disease and towards extending the life span of these animals. This has demonstrated both the beneficial effects of calorie restriction on lifespan extension and the overall impact of slowing the aging process compared to curing the major diseases of aging:

Gene expression data from BioMarker experiments indicate that even a brief period of caloric restriction produces about 70% of the changes associated with life span extension. This strongly indicates that nutraceuticals and pharmaceuticals can be successfully designed to mimic the healthful impact of CR and other life extending models.

Separate studies have also shown that three types of dwarf mice mutation 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 are concurrently identifying the gene expression biomarkers associated with this model of life span extension.

The BioMarker Approach Altogether, BioMarker scientists study longevity-related expression in over 12,000 genes in mice using cDNA microarray chips. These gene changes are correlated with a number of significant healthful proteomic and cellular changes. BioMarker’s product design approach, then, is straightforward: We evaluate the genomic and proteomic response to a model of life extension (such as CR) under controlled studies; We identify the gene and protein biomarkers associated with this response; We then use these biomarkers to assess the degree of overlap between the model and various tested interventions (whether nutritionals, foods, bioactives, natural products, or drug candidates); and This guides our development of the optimal ‘mimetic’ intervention. CR and other life extending models clearly can help an individual maintain healthy, youthful gene and protein expression related to a number of biopathways associated with age and age-related disease. If we are successful, our mimetic interventions should allow us to: Delay or prevent the onset of cancer, diabetes, heart disease and neurological disorders ; Preserve or enhance the immune responsiveness of older individuals; Increase insulin sensitivity and glucose disposal; Reduce inflammatory response, and improve heart and blood vessel health; and Prolong the healthy period near the end of life, and extend the maximum healthy life span.

We are using this aging-intervention technology portfolio to move ahead with nutraceutical and personalized diagnostic products, as well as pharmaceutical therapies. Please see the links to the left to learn more, and to read an encapsulated description of our technology platform.

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