Antoaneta Sawyer, Ph.D.
There is an amazing anti-aging novelty published March 5 (2010) in Science, coming from the famous UCSD School of Medicine. Proteins called “sestrins” have been discovered that may serve as natural inhibitors of aging and age-related pathologies in fruit flies. The research was funded by the National Institutes of Health, the Superfund Basic Research Program and American Cancer Society.
Sestrins are small proteins produced in high amount by the human cells in time of elevated stress. Stress disrupts normal hormonal levels, influencing immune system strength and eating habits (Innes, Vincent & Taylor, 2007). People who are not able to handle stress show high blood sugar and decreased release of insulin from the pancreas (Viner, Mc Grath & Trudinger, 1996). Extreme emotional stress (grief, anger, worry, fear) can cause the “broken heart syndrome “(BHS), also known as Cardiomyopathy (Kim, 2009; Innes et al., 2007).
Karin, the lead author of this study, states that sestrins function, however, remained puzzling until the team found that these proteins are activators of two enzymes- protein kinases that serve as main components of a signaling pathway that is a central regulator of aging and metabolism. The first enzyme is an AMP-dependent protein kinase (AMPK), and the second called TOR works as inhibitor of the Target of Rapamycin. Both enzymes are believed to be the central regulators of aging and metabolism in a variety of model organisms, including the worm- Caenorhabditis elegans, the fruit fly- Drosophila melanogaster and mammals. There is only one major difference - while the enzyme AMPK is activated in response to caloric restriction (a condition that is already known to slow down aging), the enzyme TOR is activated in response to over-nutrition (a condition that accelerates preliminary aging). At the same time activation of AMPK inhibits TOR, and drugs that activate AMPK or inhibit TOR can delay aging in several in vivo models including mammals.
Most importantly, the biochemical imbalance resulted in several age-related pathologies. “Strikingly, the pathologies caused by the sestrin deficiency included accumulation of triglycerides, cardiac arrhythmia and muscle degeneration that occurred in rather young flies,” concluded the lead author of the study. “These pathologies are amazingly similar to the major disorders of overweight, heart failure and muscle loss that accompany aging in humans.”How exactly the body keeps the activity of these two protein kinases in balance to prevent premature aging was not known until now. Additionally, the presence of three different genes encoding sestrins in mammals made it difficult to identify their exact physiological function in live animals. The organism that reminds to mammals is the fruit fly Drosophila, whose AMPK-TOR is regulated and balanced by a single sestrin gene. Said with other words-this sestrin gene is needed to keep the anti-aging pathway in check.
Using a variety of genetic techniques, the researchers inactivated the sestrin gene of Drosophila and found that although “sestrin deficient” flies do not exhibit any developmental abnormalities, they suffer from under-activation of AMPK and over-activation of TOR – again confirming that sestrin is needed to keep the pathway in check. UCSD and the Sanford-Burnham Institute in La Jolla, California, went on to demonstrate that drugs that either activate AMPK or inhibit TOR offered protection against most of these preliminary aging, in flies. The researchers also found that over-activation of TOR is likely to accelerate aging of heart and skeletal muscles by disrupting an important “quality control” process called “autophagy.” Autophagy is a process that allows cells to rid themselves or replace damaged mitochondria, the little energy centrals that provide all cells, with energy. However, when mitochondria get old, they produce high concentrations of free radicals that can lead to consequent tissue damage. The authors explained that the process of autophagy – which counteracts aging – allows the replacement of “old” and defective mitochondria with “young” and completely new mitochondria. At the same time- “sestrin-deficient” flies were found to exhibit accumulation of damaged mitochondria and ROS several days prior to the detection of tissue (in this case- muscle) degeneration. Feeding these flies vitamin E, an antioxidant which neutralizes free radicals, prevented premature aging a d muscle degeneration and heart failure.
In the future, the same group of researchers is planning to examine whether the mammalian sestrins can also control aging and metabolism, and whether defects in their proper gene expression will provide the explanation to some of the currently unexplainable degenerative diseases associated with old age. “Maybe one day we will be able to use sestrin analogs to prevent much of the tissue failure associated with aging, as well as treat a number of degenerative diseases, whose incidence goes up with old age, including sarcopenia and Alzheimer’s disease,” recapitulated Karin. The team of researchers proved that their structure and biochemical function found in both, flies and humans may regulate a signaling pathway that is a central controller of aging and metabolism
There is an amazing anti-aging novelty published March 5 (2010) in Science, coming from the famous UCSD School of Medicine. Proteins called “sestrins” have been discovered that may serve as natural inhibitors of aging and age-related pathologies in fruit flies. The research was funded by the National Institutes of Health, the Superfund Basic Research Program and American Cancer Society.
Sestrins are small proteins produced in high amount by the human cells in time of elevated stress. Stress disrupts normal hormonal levels, influencing immune system strength and eating habits (Innes, Vincent & Taylor, 2007). People who are not able to handle stress show high blood sugar and decreased release of insulin from the pancreas (Viner, Mc Grath & Trudinger, 1996). Extreme emotional stress (grief, anger, worry, fear) can cause the “broken heart syndrome “(BHS), also known as Cardiomyopathy (Kim, 2009; Innes et al., 2007).
Karin, the lead author of this study, states that sestrins function, however, remained puzzling until the team found that these proteins are activators of two enzymes- protein kinases that serve as main components of a signaling pathway that is a central regulator of aging and metabolism. The first enzyme is an AMP-dependent protein kinase (AMPK), and the second called TOR works as inhibitor of the Target of Rapamycin. Both enzymes are believed to be the central regulators of aging and metabolism in a variety of model organisms, including the worm- Caenorhabditis elegans, the fruit fly- Drosophila melanogaster and mammals. There is only one major difference - while the enzyme AMPK is activated in response to caloric restriction (a condition that is already known to slow down aging), the enzyme TOR is activated in response to over-nutrition (a condition that accelerates preliminary aging). At the same time activation of AMPK inhibits TOR, and drugs that activate AMPK or inhibit TOR can delay aging in several in vivo models including mammals.
Most importantly, the biochemical imbalance resulted in several age-related pathologies. “Strikingly, the pathologies caused by the sestrin deficiency included accumulation of triglycerides, cardiac arrhythmia and muscle degeneration that occurred in rather young flies,” concluded the lead author of the study. “These pathologies are amazingly similar to the major disorders of overweight, heart failure and muscle loss that accompany aging in humans.”How exactly the body keeps the activity of these two protein kinases in balance to prevent premature aging was not known until now. Additionally, the presence of three different genes encoding sestrins in mammals made it difficult to identify their exact physiological function in live animals. The organism that reminds to mammals is the fruit fly Drosophila, whose AMPK-TOR is regulated and balanced by a single sestrin gene. Said with other words-this sestrin gene is needed to keep the anti-aging pathway in check.
Using a variety of genetic techniques, the researchers inactivated the sestrin gene of Drosophila and found that although “sestrin deficient” flies do not exhibit any developmental abnormalities, they suffer from under-activation of AMPK and over-activation of TOR – again confirming that sestrin is needed to keep the pathway in check. UCSD and the Sanford-Burnham Institute in La Jolla, California, went on to demonstrate that drugs that either activate AMPK or inhibit TOR offered protection against most of these preliminary aging, in flies. The researchers also found that over-activation of TOR is likely to accelerate aging of heart and skeletal muscles by disrupting an important “quality control” process called “autophagy.” Autophagy is a process that allows cells to rid themselves or replace damaged mitochondria, the little energy centrals that provide all cells, with energy. However, when mitochondria get old, they produce high concentrations of free radicals that can lead to consequent tissue damage. The authors explained that the process of autophagy – which counteracts aging – allows the replacement of “old” and defective mitochondria with “young” and completely new mitochondria. At the same time- “sestrin-deficient” flies were found to exhibit accumulation of damaged mitochondria and ROS several days prior to the detection of tissue (in this case- muscle) degeneration. Feeding these flies vitamin E, an antioxidant which neutralizes free radicals, prevented premature aging a d muscle degeneration and heart failure.
In the future, the same group of researchers is planning to examine whether the mammalian sestrins can also control aging and metabolism, and whether defects in their proper gene expression will provide the explanation to some of the currently unexplainable degenerative diseases associated with old age. “Maybe one day we will be able to use sestrin analogs to prevent much of the tissue failure associated with aging, as well as treat a number of degenerative diseases, whose incidence goes up with old age, including sarcopenia and Alzheimer’s disease,” recapitulated Karin. The team of researchers proved that their structure and biochemical function found in both, flies and humans may regulate a signaling pathway that is a central controller of aging and metabolism
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