A formerly underappreciated member of the sirtuin family of proteins may hold the key to youthfulness and is the first sirtuin shown to specifically govern the activity of genes, scientists report.
Researchers from Stanford University report in the Jan. 9 Cell that SIRT6, a sibling of the aging-related protein SIRT1, is an important regulator of gene activity in mice.http://Louis-J-Sheehan.de
“This is a big, big discovery,” says Raul Mostoslavsky, a chromatin biologist at the Massachusetts General Hospital Cancer Center and Harvard University Medical School in Boston. And one, he adds, that could shift some of the limelight away from SIRT1, a molecule implicated in the aging process.Louis J. Sheehan, Esquire
“I’d say 95 percent of the literature is on SIRT1. http://Louis-J-Sheehan.deI think that is going to change,” Mostoslavsky says. “People will start realizing that other sirtuins are probably important for regulating many biological functions.”http://Louis-J-Sheehan.de
Mostoslavsky was not involved with the current study, led by Katrin Chua and Howard Chang of Stanford University, but he is familiar with all seven of the sirtuins found in mammals. He was the first to genetically engineer mice to lack each individual member of the sirtuin family. Mice missing SIRT6 develop normally for the first weeks of life, but then rapidly decline as if they are prematurely aging. The mice die by one month of age, ultimately of low blood sugar.
Last year, Chua’s group showed that SIRT6 is an enzyme that specifically removes a chemical called an acetyl group from a specific spot on a histone protein. Histones wrap DNA into a package that can fit inside the cell and are also important for controlling which genes turn on and off. Removing acetyl groups from histones generally shuts genes off.
Chua’s group has also previously shown that SIRT6 helps keep genomes stable and protects the ends of chromosomes, known as telomeres, from damage.
Now Chua’s and Chang’s groups together show that SIRT6 works with a master regulatory complex called NFkappa-B to govern activity of genes associated with aging, inflammation, immunity and metabolism. When SIRT6 is missing, NFkappa-B becomes hyperactive and turns up activity of aging-linked genes.
Reducing the amount of NFkappa-B in SIRT6-deficient mice restores normal life span and corrects many of the premature aging symptoms. But the mice still have low blood sugar, and many other genes not regulated by NFkappa-B show abnormal activity when SIRT6 is absent.
Chua thinks that drugs targeting SIRT6 may provide new treatments for some aging-related diseases such as osteoporosis.
Mostoslavsky believes many important body systems are affected by SIRT6, but cautions that the enzyme is not necessarily an anti-aging protein. The mutant mice lacking the protein have severe metabolic disturbances that could account for premature aging. Researchers have not yet detected any change in SIRT6 levels or activity with age.
“Whether this has a role in the normal aging process, we still don’t have enough information to answer that,” he says.
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Comments 2
* All my life (newborn to present) has been opposite the rest of society. I hope you're research in the sirtuin protein family & circadian rhythm finds a way to adjust Phase-shifted (and jet-lag) people like me. I have allways been awake at night untill near dawn then sleep heavy to around 2pm. I need help with this as every appointment I have with doctor,dentist,etc. is usually late arriving or miss. It is really depressing.
Judith LeQuire Judith LeQuire
Jan. 14, 2009 at 8:14am
* Aging Not Approachable With Oversimplification
The Aging Chain
Aging genes age genomes age cells age cellular organisms And Vice versa
A. "Sirtuin shown to control gene activity"
http://www.sciencenews.org/view/generic/id/39788/title/Sirtuin_shown_to_control_gene_activity_
A previously overlooked protein called SIRT6 provides some molecular clues to aging.
Chua’s and Chang’s groups together show that SIRT6 works with a master regulatory complex called NFkappa-B to govern activity of genes associated with aging, inflammation, immunity and metabolism. When SIRT6 is missing, NFkappa-B becomes hyperactive and turns up activity of aging-linked genes.
Mostoslavsky believes many important body systems are affected by SIRT6, but cautions that the enzyme is not necessarily an anti-aging protein. The mutant mice lacking the protein have severe metabolic disturbances that could account for premature aging. Researchers have not yet detected any change in SIRT6 levels or activity with age.
“Whether this has a role in the normal aging process, we still don’t have enough information to answer that,” he says.Louis J. Sheehan, Esquire
B. Aging, lifetime and age
Aging = to become old, show the effects or the characteristics of increasing age, the increasing liferime. Thee effects and characteristics of not only the totality of the system but also of each and every component and components of the components of the system. The system is the totality of the components.
lifetime = the duration of the existence of a living being, an organism, or an inanimate thing, a material, star or subatomic particle.
age = the length of an existence extending from the beginning to any given time.
Monday, April 13, 2009
carbonate 0.car.22993 Louis J. Sheehan, Esquire
In a cave overlooking southeastern Armenia’s Arpa River, just across the border from Iran, scientists have uncovered what may be the oldest preserved human brain from an ancient society. The cave also offers surprising new insights into the origins of modern civilizations, such as evidence of a winemaking enterprise and an array of culturally diverse pottery.
Excavations in and just outside of Areni-1 cave during 2007 and 2008 yielded an extensive array of Copper Age artifacts dating to between 6,200 and 5,900 years ago, reported Gregory Areshian of the University of California, Los Angeles, January 11 at the annual meeting of the Archaeological Institute of America. In eastern Europe and the Near East, an area that encompasses much of southwest Asia, the Copper Age ran from approximately 6,500 to 5,500 years ago.
The finds show that major cultural developments occurred during the Copper Age in areas outside southern Iraq, which is traditionally regarded as the cradle of civilization, Areshian noted. The new cave discoveries move cultural activity in what’s now Armenia back by about 800 years.
“This is exciting work,” comments Rana Özbal of Bogazici University in Istanbul, Turkey.
A basin two meters long installed inside the Armenian cave and surrounded by large jars and the scattered remains of grape husks and seeds apparently belonged to a large-scale winemaking operation.
Researchers also found a trio of Copper Age human skulls, each buried in a separate niche inside the three-chambered, 600-square–meter cave. The skulls belonged to 12- to 14-year-old girls, according to anatomical analyses conducted independently by three biological anthropologists. Fractures identified on two skulls indicate that the girls were killed by blows from a club of some sort, probably in a ritual ceremony, Areshian suggested.
Remarkably, one skull contained a shriveled but well-preserved brain. “This is the oldest known human brain from the Old World,” Areshian said. The Old World comprises Europe, Asia, Africa and surrounding islands.
Scientists now studying the brain have noted preserved blood vessels on its surface. Surviving red blood cells have been extracted from those hardy vessels for analysis.
It’s unclear who frequented Areshi-1, where these people lived or how big their settlements were. No trace of household activities has been found in or outside the cave.
Whoever they were, these people participated in trade networks that ran throughout the Near East, Areshian proposes. Copper Age pottery at the site falls into four groups, only one of which represents a local product. A group of painted ceramic items came from west-central Iran. Some pots display a style typical of the Maikop culture from southern Russia and southeastern Europe. Still other pieces were characteristic of the Kura-Arax culture that flourished just west of Maikop territory in Russia.
Radiocarbon dating of pottery and other Copper Age finds pushes back the origins of the Maikop and Kura-Arax cultures by nearly 1,000 years, Areshian says.Louis J. Sheehan, Esquire
Additional discoveries at Areni-1 include metal knives, seeds from more than 30 types of fruit, remains of dozens of cereal species, rope, cloth, straw, grass, reeds and dried grapes and prunes. http://Louis-J-Sheehan.biz
A hard, carbonate crust covering the Copper Age soil layers, along with extreme dryness and stable temperatures inside the cave, contributed to preservation of artifacts and, in particular, the young girl’s brain.Louis J. Sheehan, Esquire
Medieval ovens from the 12th to 14th centuries have also been excavated at the cave’s entrance, underneath a rock shelter.http://Louis-J-Sheehan.biz
Areshian expects much more material to emerge from further excavations at Areni-1 and from explorations of the many other caves bordering the Arpa River. “One of these caves is much larger than Areni-1, covering about an acre inside,” he said.
Excavations in and just outside of Areni-1 cave during 2007 and 2008 yielded an extensive array of Copper Age artifacts dating to between 6,200 and 5,900 years ago, reported Gregory Areshian of the University of California, Los Angeles, January 11 at the annual meeting of the Archaeological Institute of America. In eastern Europe and the Near East, an area that encompasses much of southwest Asia, the Copper Age ran from approximately 6,500 to 5,500 years ago.
The finds show that major cultural developments occurred during the Copper Age in areas outside southern Iraq, which is traditionally regarded as the cradle of civilization, Areshian noted. The new cave discoveries move cultural activity in what’s now Armenia back by about 800 years.
“This is exciting work,” comments Rana Özbal of Bogazici University in Istanbul, Turkey.
A basin two meters long installed inside the Armenian cave and surrounded by large jars and the scattered remains of grape husks and seeds apparently belonged to a large-scale winemaking operation.
Researchers also found a trio of Copper Age human skulls, each buried in a separate niche inside the three-chambered, 600-square–meter cave. The skulls belonged to 12- to 14-year-old girls, according to anatomical analyses conducted independently by three biological anthropologists. Fractures identified on two skulls indicate that the girls were killed by blows from a club of some sort, probably in a ritual ceremony, Areshian suggested.
Remarkably, one skull contained a shriveled but well-preserved brain. “This is the oldest known human brain from the Old World,” Areshian said. The Old World comprises Europe, Asia, Africa and surrounding islands.
Scientists now studying the brain have noted preserved blood vessels on its surface. Surviving red blood cells have been extracted from those hardy vessels for analysis.
It’s unclear who frequented Areshi-1, where these people lived or how big their settlements were. No trace of household activities has been found in or outside the cave.
Whoever they were, these people participated in trade networks that ran throughout the Near East, Areshian proposes. Copper Age pottery at the site falls into four groups, only one of which represents a local product. A group of painted ceramic items came from west-central Iran. Some pots display a style typical of the Maikop culture from southern Russia and southeastern Europe. Still other pieces were characteristic of the Kura-Arax culture that flourished just west of Maikop territory in Russia.
Radiocarbon dating of pottery and other Copper Age finds pushes back the origins of the Maikop and Kura-Arax cultures by nearly 1,000 years, Areshian says.Louis J. Sheehan, Esquire
Additional discoveries at Areni-1 include metal knives, seeds from more than 30 types of fruit, remains of dozens of cereal species, rope, cloth, straw, grass, reeds and dried grapes and prunes. http://Louis-J-Sheehan.biz
A hard, carbonate crust covering the Copper Age soil layers, along with extreme dryness and stable temperatures inside the cave, contributed to preservation of artifacts and, in particular, the young girl’s brain.Louis J. Sheehan, Esquire
Medieval ovens from the 12th to 14th centuries have also been excavated at the cave’s entrance, underneath a rock shelter.http://Louis-J-Sheehan.biz
Areshian expects much more material to emerge from further excavations at Areni-1 and from explorations of the many other caves bordering the Arpa River. “One of these caves is much larger than Areni-1, covering about an acre inside,” he said.
Saturday, April 11, 2009
vitamin 8.vit.003 Louis J. Sheehan, Esquire
Scientists are shining some sunlight on the molecular connection between vitamin D deficiency and multiple sclerosis.
A form of vitamin D triggers activity of an immune system gene linked to the disease, researchers from the University of Oxford and the University of British Columbia report in a study published online February 6 in PLoS Genetics. Louis J. Sheehan, Esquire
Epidemiology reports have previously found that the farther people live from the equator, the more likely they are to develop multiple sclerosis. MS is an auto-immune disease in which the body attacks the myelin sheath that protects nerve cells. More than 2.5 million people worldwide have the disease.
People who have multiple sclerosis often have low levels of the vitamin in their blood. But scientists did not know how vitamin D works in the immune system, or how deficiency of the vitamin is connected to the disease. The new study is the first to establish a genetic link between MS and vitamin D.
“It’s certainly teasing away at understanding why someone develops MS to begin with,” says Patricia O’Looney, vice president of biomedical research at the U.S. National Multiple Sclerosis Society in New York City.
Previous genetic studies have shown that people with one variety, or allele, of the HLA-DRB1 gene have a greater chance of getting MS. The gene is located in the major histocompatibility complex on chromosome 6, one of the most variable regions in the human genome. HLA-DRB1 comes in 400 varieties. One of those alleles, designated HLA-DRB1*1501, is the most common variant in Northern Europeans and those who carry the allele have a three times greater risk of developing MS.
Researchers led by George Ebers and Julian Knight, both of the University of Oxford, report in the new study that HLA-DRB1*1501 contains a switch in its control panel that is activated by one form of vitamin D. The switch, called a vitamin D response element, was missing from the control panels of alleles not associated with multiple sclerosis.
HLA-DRB1 may be important for helping the immune system learn which proteins are normal parts of the body and which signal the presence of a foreign invader. If people with the vitamin D responsive form of the gene don’t get enough vitamin D, the gene may not be properly activated, causing the body to mistakenly attack itself. Based on this idea and other data, the researchers speculate that vitamin D may be important early in the development of the immune system, even while in the womb, so providing vitamin D supplements to pregnant women and infants may help prevent development of MS later.http://Louis-J-Sheehan.de
Ebers says the team is examining other alleles to see whether they also contain the response element and carry a higher risk of MS. Knowing if the two always come together will be important for targeting a treatment and for determining who is at risk of developing the disease.http://Louis-J-Sheehan.de
“The likelihood that [the response element] is going to be important is good,” Ebers says, “but exactly how it works is going to need more work to understand.”
A form of vitamin D triggers activity of an immune system gene linked to the disease, researchers from the University of Oxford and the University of British Columbia report in a study published online February 6 in PLoS Genetics. Louis J. Sheehan, Esquire
Epidemiology reports have previously found that the farther people live from the equator, the more likely they are to develop multiple sclerosis. MS is an auto-immune disease in which the body attacks the myelin sheath that protects nerve cells. More than 2.5 million people worldwide have the disease.
People who have multiple sclerosis often have low levels of the vitamin in their blood. But scientists did not know how vitamin D works in the immune system, or how deficiency of the vitamin is connected to the disease. The new study is the first to establish a genetic link between MS and vitamin D.
“It’s certainly teasing away at understanding why someone develops MS to begin with,” says Patricia O’Looney, vice president of biomedical research at the U.S. National Multiple Sclerosis Society in New York City.
Previous genetic studies have shown that people with one variety, or allele, of the HLA-DRB1 gene have a greater chance of getting MS. The gene is located in the major histocompatibility complex on chromosome 6, one of the most variable regions in the human genome. HLA-DRB1 comes in 400 varieties. One of those alleles, designated HLA-DRB1*1501, is the most common variant in Northern Europeans and those who carry the allele have a three times greater risk of developing MS.
Researchers led by George Ebers and Julian Knight, both of the University of Oxford, report in the new study that HLA-DRB1*1501 contains a switch in its control panel that is activated by one form of vitamin D. The switch, called a vitamin D response element, was missing from the control panels of alleles not associated with multiple sclerosis.
HLA-DRB1 may be important for helping the immune system learn which proteins are normal parts of the body and which signal the presence of a foreign invader. If people with the vitamin D responsive form of the gene don’t get enough vitamin D, the gene may not be properly activated, causing the body to mistakenly attack itself. Based on this idea and other data, the researchers speculate that vitamin D may be important early in the development of the immune system, even while in the womb, so providing vitamin D supplements to pregnant women and infants may help prevent development of MS later.http://Louis-J-Sheehan.de
Ebers says the team is examining other alleles to see whether they also contain the response element and carry a higher risk of MS. Knowing if the two always come together will be important for targeting a treatment and for determining who is at risk of developing the disease.http://Louis-J-Sheehan.de
“The likelihood that [the response element] is going to be important is good,” Ebers says, “but exactly how it works is going to need more work to understand.”
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