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Looking for a Way to Cure Aging

Prof. Linda Partridge Discusses Her Research on Senescence

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Looking for a Way to Cure Aging

Dr. Linda Partridge

EMBO

At the 2012 European Molecular Biology Organization (EMBO) meeting, Dr. Linda Partridge talked about the connection between aging and the biological pathway for nutrient sensing. Nutrient sensing is not exactly the same as nutrition in the sense of what foods are healthy to eat. Nutrient sensing has to do with the protein and gene interactions that enable the body to sense what we eat, and respond by stimulating growth and activating various metabolic pathways. It seems the same proteins and genes involved in this process also regulate the aging process, also known as senescence.

The Connection Between Nutrients and Aging

There appears to be close connection between this nutrient sensing pathway and the complex biological process of aging. It has been known for years that severe diet restriction, basically a very low calorie diet that provides essential nutrients, actually extends the life of most animals. The observation that limited calorie diets extend the life of lab mice and rats by more than 25% was first published in 1935. Later research found a similar phenomena occurs in yeast, fruit flies, rats, and monkeys (although one recent study has produced some conflicting results regarding the situation with monkeys).

Long term controlled studies of caloric restriction on humans is not available for obvious reasons. However, Dr. Partridge did mention that she has met a few people attempting to live on a calorie restricted diet and, while she didn't know the effect of it on their health, they were not very happy people. A restricted regimen of calories similar to what is provided to mice and rats in the lab is very severe.

The Aging Program

While many researchers have looked for general metabolic reasons for the life extension response to caloric restriction, Dr. Partridge has focused on trying to work out the essential genetic interactions that produce this effect. What she and a few other researchers that have taken this gene-based approach seem to have discovered is that there appears to be an underlying biological process that produces the aging effect.

Aging manifests as a very complex constellation of conditions including wrinkled dry skin, declining eyesight, poorer hearing, arthritis, the development of cataracts, and with these physical changes, a sharply rising incidence of serious health conditions such as cardiovascular disease, diabetes, dementia, and cancer. The leading risk factor for these disease and several others is simply age. It seems that all the body’s systems are falling apart and most people think of this as a general wearing out of the body. However, the science indicates that an underlying genetic program may be at the root of these age associated changes.

Genetics Influences Aging

Dr. Partridge suggested that perhaps it shouldn’t be surprising that there appears to be very fundamental biological controls at the core of aging. There is no simple explanation why mice typically live barely 2 years while baleen whales, another mammal, lives over 200. While there is a vague correlation between animal size and life span across all animals, it is certainly not consistent or predictable. Larger dogs have shorter life spans than small ones. Most rodents have very short life spans but some porcupine species and the ugly naked mole rat have lifespans of more than 20 years. The Brandt’s myotis bat can live 40 years. Outside of mammals, many birds have quite long lives. Parrot life expectancy is on par with humans. Clearly, there is some underlying genetic control managing the aging program.

Finding Aging Genes

Dr. Partridge's colleague David Gems made the first age-related gene breakthrough when he found the aging process could be significantly altered in nematodes worms with a mutation in just one gene. In fact, he actually found that, if any of three different genes were mutated, lifespan of the worms increased. These genes were for components of the insulin receptor pathway, the series of interacting proteins that respond after the hormone insulin triggers its receptor on the cell membrane. Here we have the connection between aging and nutrient sensing—insulin controls food metabolism.

Overlap Between Aging Genetics and Metabolism

Dr. Partridge’s lab extended Dr. Gems' work by showing that similar genetic alternations in flies and mice also extend the life of these animals. Further, they showed that the effect was very similar to the extension that occurs with dietary restriction.

Even more interestingly though, her lab went on to show that in fruit flies, and preliminarily in mice, life extension does not correlate with limiting all calories but just protein. Further, it seems to be just certain amino acids that make up proteins, ones that are essential, that seem to be responsible for the life extension effect. Of course, the specific requirements are not so simple and the Partridge labs are in the midst of working out the details. However, what is clear is that regulators in the insulin sensing pathway cause significant changes on the overall aging process for both flies and mice.

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