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US researchers find key link in muscle-wasting syndrome
SCIENCE AND MEDICINE
US researchers find key link in muscle-wasting syndrome
A
lthough researchers are still struggling to unravel the cause of diseases such as cancer and AIDS, the related muscle-wasting syndrome, cachexia, associated with these and other diseases continues to pose many questions. Now researchers have found one of the key factors that leads to the breakdown of muscle, thus providing a potentially viable therapeutic target for improved intervention. Cachexia is responsible for one third of cancer mortalities—independent of tumour burden or metastases—and has been documented for more than a century. Yet little is known about the condition to enable effective management. Researchers at the Lineberger Comprehensive Cancer Centre, University of North Carolina, USA, therefore did a series of in-vitro and in-vivo experiments in mice looking at the cytokine protein tumour necrosis factor (TNF), long known to have a role in inducing cachexia. TNF was found to activate the transcription
factor NF-kB, which in turn suppresses MyoD, normally required for muscle function and repair (Science 2000: 289: 2363–66). Earlier studies have suggested that TNF does not act alone in promoting the muscle wasting associated with cachexia, implicating the presence and role of at least one other factor. TNF, in conjunction with interferon gamma, was found to reduce greatly MyoD expression. However, inhibiting NF-kB activity while maintaining the presence of TNF and interferon gamma did not repress the expression of MyoD or the critical muscle structural protein MHC in muscle. “We already knew that there were elevated TNF levels in patients with cachexia”, says lead investigator Albert Baldwin. “Now we’ve found two main pieces of the puzzle that fit between TNF and muscle wasting that occurs in cachexia. While cachexia isn’t strictly about muscle wasting but can also affect fat and adipose tissues, we believe that this
Is the human lifespan limitless? year for every two decades until he maximum age at death for 1970, when the average maximum human beings has been increasage was 105 years, and then a suding steadily for more than a century den acceleration to 1 year for every and shows no signs of slowing down, decade, or about age 108 years, in says demographer John Wilmoth the 1990s. The analysis showed that (University of California, Berkeley, the increases in lifespan are the result CA, USA). “Contrary to the comof medical and publicmon belief that has health advances made been stated in many Rights were throughout the censcientific papers, there tury, not because of a is no ‘fixed limit’ to the not granted to larger population base. human lifespan”, include this The upward spurt in explains Wilmoth. the 1970s is attribut“People have said that image in able mainly to reducyou can extend the electronic tions in mortality average lifespan but not among people older the maximum—that media. Please than 70 years (Science eventually you’d bump refer to the 2000; 289: 2366–68). up against this limit printed “People have been where lifespan can’t saying for a long time increase any more journal. that humans can’t live unless you genetically beyond 120 years, but alter the organism. But that number was taken we’re showing that you Record breaking Calment out of thin air”, can’t draw the line and emphasises Wilmoth. “We’ve already say ‘beyond this age, no one can had a well-documented case of live.”’ someone who lived to age 122 Wilmoth and co-workers analysed [Jeanne Calment, who died in Swedish national demographic data France in 1997]. It wouldn’t surprise from 1861 to 1999, the longest availme if the world record is 125 or 150 able series of reliable information on by the year 2050”, he predicts. the upper limits of achieved human lifespan. They found a gain in the maximum age at death of about 1 Marilynn Larkin
T
THE LANCET • Vol 356 • October 7, 2000
research may help to shed light on the muscle wasting component of this syndrome”. “This is very exciting news”, says Gail Gazelle (Harvard Vanguard Medical Associates, MA, USA). “The study is part of an evolution in our understanding of what happens at a cellular and biochemical level in cachexia”. Gazelle believes that, given the focus on the molecular and cellular components of cachexia, the research constitutes another important piece of the puzzle that may lead to pharmacological or genetic routes for the management of cachexia, hopefully in 5–10 years. Results with current therapies for cachexia (eg, the steroid dexamethasone) have been varied, she explains, “so this field is ripe for this kind of finding and the clinical application thereof”, she adds. The researchers think that it may take 1 or 2 years before embarking on human trials. Angela Pirisi
News in Brief New hope for muscle spacicity Dysport, a derivative of botulinum toxin type A, can reduce the pain and muscle spasms that often paralyse a limb after a stoke, according to a report published in the October issue of Stroke. The drug was injected to target specific muscle groups, leaving other muscles unaffected. The authors suggest that this offers distinct advantages over oral drugs which reduce muscle tone throughout the body. Furthermore, a single injection is effective for 3–4 months, whereas oral medications often need to be taken daily. Garlic protects against cancer A meta-analysis published in the October issue of American Journal of Clinical Nutrition suggests that individuals who consume raw or cooked garlic regularly are less likely to develop stomach or colorectal cancer than non-garlic consumers. Previous research has shown that a compound in garlic called allium partially protects animals against cancer, and the authors speculate that this might explain the current findings.
1249
For personal use only. Not to be reproduced without permission of The Lancet.
US researchers find key link in muscle-wasting syndrome
A
lthough researchers are still struggling to unravel the cause of diseases such as cancer and AIDS, the related muscle-wasting syndrome, cachexia, associated with these and other diseases continues to pose many questions. Now researchers have found one of the key factors that leads to the breakdown of muscle, thus providing a potentially viable therapeutic target for improved intervention. Cachexia is responsible for one third of cancer mortalities—independent of tumour burden or metastases—and has been documented for more than a century. Yet little is known about the condition to enable effective management. Researchers at the Lineberger Comprehensive Cancer Centre, University of North Carolina, USA, therefore did a series of in-vitro and in-vivo experiments in mice looking at the cytokine protein tumour necrosis factor (TNF), long known to have a role in inducing cachexia. TNF was found to activate the transcription
factor NF-kB, which in turn suppresses MyoD, normally required for muscle function and repair (Science 2000: 289: 2363–66). Earlier studies have suggested that TNF does not act alone in promoting the muscle wasting associated with cachexia, implicating the presence and role of at least one other factor. TNF, in conjunction with interferon gamma, was found to reduce greatly MyoD expression. However, inhibiting NF-kB activity while maintaining the presence of TNF and interferon gamma did not repress the expression of MyoD or the critical muscle structural protein MHC in muscle. “We already knew that there were elevated TNF levels in patients with cachexia”, says lead investigator Albert Baldwin. “Now we’ve found two main pieces of the puzzle that fit between TNF and muscle wasting that occurs in cachexia. While cachexia isn’t strictly about muscle wasting but can also affect fat and adipose tissues, we believe that this
Is the human lifespan limitless? year for every two decades until he maximum age at death for 1970, when the average maximum human beings has been increasage was 105 years, and then a suding steadily for more than a century den acceleration to 1 year for every and shows no signs of slowing down, decade, or about age 108 years, in says demographer John Wilmoth the 1990s. The analysis showed that (University of California, Berkeley, the increases in lifespan are the result CA, USA). “Contrary to the comof medical and publicmon belief that has health advances made been stated in many Rights were throughout the censcientific papers, there tury, not because of a is no ‘fixed limit’ to the not granted to larger population base. human lifespan”, include this The upward spurt in explains Wilmoth. the 1970s is attribut“People have said that image in able mainly to reducyou can extend the electronic tions in mortality average lifespan but not among people older the maximum—that media. Please than 70 years (Science eventually you’d bump refer to the 2000; 289: 2366–68). up against this limit printed “People have been where lifespan can’t saying for a long time increase any more journal. that humans can’t live unless you genetically beyond 120 years, but alter the organism. But that number was taken we’re showing that you Record breaking Calment out of thin air”, can’t draw the line and emphasises Wilmoth. “We’ve already say ‘beyond this age, no one can had a well-documented case of live.”’ someone who lived to age 122 Wilmoth and co-workers analysed [Jeanne Calment, who died in Swedish national demographic data France in 1997]. It wouldn’t surprise from 1861 to 1999, the longest availme if the world record is 125 or 150 able series of reliable information on by the year 2050”, he predicts. the upper limits of achieved human lifespan. They found a gain in the maximum age at death of about 1 Marilynn Larkin
T
THE LANCET • Vol 356 • October 7, 2000
research may help to shed light on the muscle wasting component of this syndrome”. “This is very exciting news”, says Gail Gazelle (Harvard Vanguard Medical Associates, MA, USA). “The study is part of an evolution in our understanding of what happens at a cellular and biochemical level in cachexia”. Gazelle believes that, given the focus on the molecular and cellular components of cachexia, the research constitutes another important piece of the puzzle that may lead to pharmacological or genetic routes for the management of cachexia, hopefully in 5–10 years. Results with current therapies for cachexia (eg, the steroid dexamethasone) have been varied, she explains, “so this field is ripe for this kind of finding and the clinical application thereof”, she adds. The researchers think that it may take 1 or 2 years before embarking on human trials. Angela Pirisi
News in Brief New hope for muscle spacicity Dysport, a derivative of botulinum toxin type A, can reduce the pain and muscle spasms that often paralyse a limb after a stoke, according to a report published in the October issue of Stroke. The drug was injected to target specific muscle groups, leaving other muscles unaffected. The authors suggest that this offers distinct advantages over oral drugs which reduce muscle tone throughout the body. Furthermore, a single injection is effective for 3–4 months, whereas oral medications often need to be taken daily. Garlic protects against cancer A meta-analysis published in the October issue of American Journal of Clinical Nutrition suggests that individuals who consume raw or cooked garlic regularly are less likely to develop stomach or colorectal cancer than non-garlic consumers. Previous research has shown that a compound in garlic called allium partially protects animals against cancer, and the authors speculate that this might explain the current findings.
1249
For personal use only. Not to be reproduced without permission of The Lancet.