Worm lifespan doubled - Cynthia Kenyon

reposted from: http://www.facebook.com/ajax/sharer/?s=99&appid=2309869772&p%5B0%5D=680125715&p%5B1%5D=239216616142237

Refs: Unlocking the Secrets of Longevity Genes; March 2006; Scientific American Magazine; by David A. Sinclair and Lenny Guarente; 8 page(s)

crabsallover highlights, key points, comments / links.

Aubrey De Grey - Channel 4 - 2006 documentary

reposted from: http://topdocumentaryfilms.com/do-you-want-to-live-forever/

crabsallover highlights, key points, comments / links.

thanks to Matthew Coussell of HASSNERS for letting me know about this 2006 Channel 4 programme.

Channel 4 Documentary says:-
 "following the revolutionary life extension and immortality ideas of this somewhat eccentric scientist, Dr. Aubrey de Grey.

This show is all about the radical ideas of a Cambridge biomedical gerontologist called Aubrey de Grey who believes that, within the next 20-30 years, we could extend life indefinitely by addressing seven major factors in the aging process.



Channel 4 Documentary continues:-
"He describes his work as Strategies for Engineered Negligible Senescence (SENS). The SENS theory describes “seven deadly things” that erode the body’s youthfulness at the cellular level, eventually leading to death by old age. Aubrey de Grey means to apply exercise, gene therapy, stem cells, and other yet-to-be-discovered methods of medicine to counteract each of these age-advancing devices:

1. Cell death and atrophy: Treatable with exercise, stem cells, and chemicals which stimulate cell division.
2. Cancerous cells: Theoretically treatable with a type of gene therapy being developed, called Whole-body Interdiction of Lengthening of Telomeres (WILT).
3. Mutant mitochondria: Mutated DNA in the mitochondria causes a number of diseases. These can be prevented by moving the mitochondrial DNA into the cell nucleus, where the rest of the DNA resides.
4. Cell senescence (unwanted cells): Fat cells and other unwanted cruft can be removed surgically, or by stimulating the immune system to attack unwanted cells.
5. Extracellular crosslinks (loss of elasticity): Certain proteins, such as those in cells making up the arteries, become too rigid over time because they bond to each other. These bonds can be broken with certain chemicals (some in clinical trials even today).
6 Extracellular junk: “Plaque” which collects between cells can be eliminated by stimulating the immune system, and/or by using peptides called “beta-breakers.”
7. Intracellular junk: Molecular garbage can be prevented from overwhelming certain cells by introducing enzymes which are known to be effective against such molecules."

reposted from: http://www.newscientist.com/article/dn21119-everyday-drugs-could-stop-cancers-before-they-hit.html?full=true

crabsallover highlights, key points, comments / links.

Aspirin, the cancer wonder drug

• 18:00 02 November 2011

If there was a daily pill you could take to reduce your risk of developing cancer, would you take it? At the very least, you would want to know the downside. Such a drug does exist, has few side effects, and can be purchased for peanuts in any pharmacy.

That wonder drug is aspirin. Evidence is piling up that a daily dose reduces the risk of dying from cancer by about a third (see "Everyday drugs could stop cancers before they hit"). For some cancers the results are even better.

As yet, there is no official advice to take aspirin to prevent cancer. Surely it can only be a matter of time. On the basis of similar – though admittedly stronger – evidence, doctors already advise millions of people to take low-dose aspirin to reduce their risk of having heart attacks and strokes. While the drug doesn't agree with everyone, severe adverse reactions are rare.

A handful of doctors claim that aspirin's benefits stem from the fact that it is a vital micronutrient which should be reclassified as a vitamin (New Scientist, 7 February 2004, p 36). That debate is still far from over. But the argument for even more widespread use of aspirin as a prophylactic is starting to look unstoppable.

Everyday drugs could stop cancers before they hit

• 18:00 02 November 2011 by Linda Geddes
• Magazine issue 2837. 

Editorial: "Aspirin, the cancer wonder drug"

People at high risk of cancer may soon be advised to take readily available drugs such as aspirin to reduce their chances of succumbing to one of the world's biggest killers.

Although cancer screening programmes already exist, offering women regular smear tests or mammograms, for example, to detect early signs of cervical or breast cancer, these look for precancerous changes to cells or suspicious lumps, rather than identifying people who are at high risk of cancer in the future. For many of these people, even those who possess a gene mutation that puts them at high risk, watchful waiting is the norm.

That could be about to change. It looks as if common drugs may be able to slash a person's chances of developing cancer – dubbed chemoprevention. "For people at high risk of cancer at least, chemoprevention is finally coming of age," says John Burn of Newcastle University, UK.

Breast cancer set the trend. Women over the age of 50 are often offered mammograms to detect early signs of cancer. Such screening has drawn controversy, as it can flag up harmless lumps as cancerous, leading women to undergo unnecessary investigation. However, mounting evidence suggests mammograms of healthy breasts might provide vital information on a woman's cancer risk in future, and that this information is not being put to good use.

"All the routine mammogram does is look for early cancers," says Jack Cuzick of the Wolfson Institute of Preventative Medicine in London. "But within this mammogram there's a lot of information about who is at risk." What's more, tamoxifen, a cheap drug that is already used to treat breast cancer, could significantly reduce the risk of the disease developing in the first place.

Several groups have found that healthy women with dense tissue in 75 per cent or more of the breast – around 5 to 10 per cent of the female population – were around four times as likely to develop breast cancer within 10 years following the diagnosis.

Breast density relates to the amount of connective and glandular tissue in the breast, and this produces hormones that can encourage cells to divide. "We think that this combination creates an environment in which changes are more likely to occur that can give rise to cancer in the future," says Norman Boyd of the Ontario Cancer Institute in Toronto, Canada.

Now, Cuzick and his colleagues have shown that treating women at high risk with tamoxifen can reduce breast density, cutting their risk of developing the most common form of breast cancer by up to 63 per cent. The results were presented at the Frontiers of Cancer Prevention Research meeting in Boston last week.

Tamoxifen does have some side effects, but for women whose mammograms suggest that they are at high risk, it could be an attractive option, says Cuzick.

Related drugs called aromatase inhibitors also show promise – one has been shown to reduce the occurrence of breast cancer by 65 per cent (The New England Journal of Medicine, DOI: 10.1056/NEJMoa1103507).

Chemoprevention isn't just focusing on breast cancer. Last week, a study in The Lancet showed that aspirin dramatically reduces the risk of developing colorectal cancer in people with a family history of the disease. "We set out to see if aspirin would prevent cancer, and it does," says Burn, who led the study.

This is especially significant for developing countries, where cancer rates are escalating at a staggering rate (see "Poor countries need cancer drugs").

Burn and his colleagues studied 861 people with a hereditary form of colorectal cancer called Lynch syndrome, who began taking two 300-milligram tablets of aspirin a day or a placebo at some point between 1999 and 2005. By 2010, there had been 19 new colorectal cancers in those who had taken aspirin and 34 in the placebo group. In people who had taken aspirin for more than two years the effects were even more pronounced (The Lancet, DOI: 10.1016/S0140-6736(11)61049-0).

"It provides the first evidence that aspirin is effective in reducing the very high risk of cancer that these individuals have," says Peter Rothwell of the University of Oxford, who earlier this year found that a daily dose of 75 mg of aspirin for more than five years reduced the risk of dying from all cancers by 34 per cent.

Both Burn and Rothwell say they now regularly take aspirin for cancer prevention, but emphasise that self-medication is a personal decision: everyone has to weigh up the pros and cons for themselves. "Up until now, the main reason to take aspirin was to prevent vascular events. I think it will become clear that cancer prevention is the main benefit of aspirin in healthy middle-aged people," says Rothwell.

Lung cancer is another disease where preventative therapy could reap rewards: especially for the millions of ex-smokers who remain at increased risk of disease. In a trial of 152 smokers and former smokers, a drug called iloprost significantly reduced abnormalities in cells lining the airways over the course of six months in those who had kicked the habit, but not in current smokers. "If this holds up, it suggests that former smokers could reduce their risk of developing lung cancer by taking a drug," says Robert Keith of the University of Denver in Colorado, who also presented his results in Boston last week. Iloprost is a synthetic version of a naturally occurring molecule called prostacyclin, which can suppress cell growth and division.

Bringing such preventative drugs to market may not be so easy, however. One of the biggest barriers is the need to test these drugs in large numbers of healthy individuals, which will inevitably produce side-effects in some people. "Chemoprevention is tremendously appealing, but it is a more difficult path to traverse than developing a therapeutic drug," says Michael Thun of the American Cancer Society.

It is also an issue for people like Cuzick, who want tamoxifen and related drugs made available as a precaution for people at high risk. "Treatment can't be the whole answer," he says. "We've got to do something about prevention."

Poor countries need cancer drugs

Surprisingly, cancer now kills more people in developing countries than malaria, AIDS and tuberculosis combined. More than 2.4 million lives could be saved each year using affordable and readily available drugs to prevent or treat cancer.

So says a report released last week by the Global Task Force on Expanded Access to Cancer Care and Control in Developing Countries(GTF.CCC).

Better drugs mean that more people in developing countries survive infectious diseases. But they are starting to fall prey to the same illnesses that strike in richer countries – cancer, cardiovascular disease and diabetes. By 2030, nearly 70 per cent of the projected 27 million new cancer cases each year will occur in those countries with the least infrastructure to deal with it. "Unless we take action now, these countries will be overwhelmed by the economic burden of disease," says David Kerr of the University of Oxford, who has set up a network of collaborations in India and Africa to improve cancer care. "It's not a success story to say we've avoided death in the first five years of life, and we've avoided death in childbirth, but we ignore what happens with cancer."

According to the report, 26 of 29 key drugs that could treat the most prevalent and curable cancers are off-patent, meaning people could receive a course of treatment for less than $100.

For example, the survival rate for childhood leukaemia in Canada is around 90 per cent, but in low-income countries, only 10 per cent survive because they do not have access to the drugs, even though they are off-patent.

"A couple of hundred million dollars would treat all of these childhood leukaemias," says Julio Frenk, Dean of Harvard School of Public Health and co-chair of the GTF.CCC. "It's just lack of access."

Low blood sugar 'affects food cravings'

reposted from: http://www.nhs.uk/news/2011/09September/Pages/blood-sugar-desire-high-calorie-foods.aspx

crabsallover highlights, key points, comments / links.

“'Good' sugar is the secret to a slim figure,” according to The Daily Telegraph. The newspaper says that a new study has found that when our blood sugar levels drop we lose our ability to control desire and feel an increased urge to eat.

During the study researchers used scans to detect brain activity following a drop in glucose, which is the blood sugar that our cells use as a source of energy. They then compared their results to the participants’ desire to eat different foods and recorded how this related to their blood sugar levels. They found that small drops in blood sugar activated the region of the brain that produces a desire to eat, while adequate levels of blood sugar activated the region of the brain that controls impulses. Activation of this regulatory part of the brain by higher levels of blood sugar was found not to occur in obese individuals.

While these are intriguing results, the study was small, only involving 14 participants. This means the results should be interpreted cautiously, as smaller sample sizes are prone to being influenced by chance.

Where did the story come from?

The study was carried out by researchers from Yale University School of Medicine and the University of Southern California Keck School of Medicine. It was funded by the US National Institutes of Health.

The study was published in the peer-reviewed Journal of Clinical Investigation.

The study was covered accurately by the media. However, no news outlets reported on the small sample size, which is a major limitation of the research. Both the Daily Mail and The Daily Telegraph reported that the results mean that maintaining glucose levels is the “secret to staying slim”, an interpretation that is not supported by this small, short-term study.

What kind of research was this?

This was a small human experiment that exposed participants to images of food and non-food, and measured how exposure to these images related to their desire for food and their brain activity under varying blood sugar conditions. The researchers aimed to detect whether the participants’ desire to eat when presented with external cues would differ according to their blood sugar levels.

The small number of participants involved in the study (14 in total) means the results should be interpreted cautiously, especially as the participants were further divided into smaller subgroups based on weight (five obese versus nine non-obese).

What did the research involve?

The researchers recruited 14 healthy participants - nine male and five female. They had an average age of 30 years and an average BMI of 25.6. Five of the participants were obese and nine were not obese.

The participants were given a lunch prepared by the researchers and then examined using a function magnetic resonance imaging (fMRI) brain scan. During the scan the researchers controlled the participants’ blood sugar by giving them varying levels of glucose and insulin intravenously. The researchers held insulin levels constant, and varied the glucose levels. Glucose levels were initially held at normal levels (euglycaemia), and then slowly dropped to low blood sugar levels (mild hypoglycaemia). This was done over the course of two hours.

During the euglycaemia and mild hypoglycaemia phases, researchers showed the participants images of high-calorie food, low-calorie food and non-food images. After each image was shown, the researchers asked the participants to rate how much they liked the item shown in the image, on a scale of 1 to 9 (higher score meant they liked it more). The researchers then asked the participants to rate how much they wanted the item shown, again on a scale of 1 to 9. The high-calorie images included pictures of cake, ice cream, lasagne, crisps and steak. The low-calorie images included pictures of fruits, vegetables and tofu.

In addition to the behavioural ratings described above, the researchers measured the participants’ brain activity when they were looking at each image. An fMRI is able to measure brain activity in real-time by detecting which brain cells are using oxygen. To activate, brain cells need both oxygen and glucose from the blood.

The researchers recorded how much the participants reported liking and wanting each item, and the areas of the brain that were activated by seeing each of the images. They then compared which brain regions were active during the normal sugar (euglycaemic) phase versus the low sugar (hypoglycaemic) phase. They also assessed whether glucose levels influenced the ability of the food pictures to affect both brain activity and the feeling of desire for food. This was assessed using the rating scale.

What were the basic results?

During the normal glucose level (euglycaemia) phase, the non-obese participants showed more activity in two areas of the brain than during the hypoglycaemia phase. These areas of the brain, the prefrontal cortex (PFC) and the anterior cingulated cortex (ACC), were significantly more active regardless of the type of image presented. These areas of the brain are responsible for controlling impulses. The difference in activation did not occur in obese participants.

During the mild hypoglycaemia, compared with the euglycaemia phase, the researchers found:

• Hunger ratings were significantly greater, with an average of 5.7 points during the hypoglycaemic phase versus an average of 4.5 points during the euglycaemic phase. Hunger ratings were similar in both the obese and non-obese participants.
• In both obese and non-obese participants, two areas of the brain called the insula and striatum were significantly more active when presented with bothigh-  hand low-calorie food images. These areas of the brain are responsible for promoting feelings of desire and craving.
• During hypoglycaemia wanting ratings were significantly higher (p=0.006) in response to high-calorie foods, but liking ratings were similar between the two phases.
• There was no difference in brain activation in response to viewing low-calorie foods.

How did the researchers interpret the results?

The researchers concluded that small drops in glucose levels set in motion “adaptive mechanisms” that specifically increase the desire for high-energy and glucose-rich foods. That is, in response to blood sugar levels decreasing, the participants’ brains responded in ways that would increase desire to eat foods that would provide them with high levels of necessary sugars. They say that this activation occurred differently in obese people from in non-obese people.

The researchers say that, further to this, they were able to identify an interaction between blood glucose levels and external cues (the sight of food) that results in a drive to eat. They say that during the normal glucose phase, the activity in the PFC area of the brain (which controls impulses) decreased the desire for food in non-obese people. During the low glucose phase, however, a different region of the brain was activated in response to the sight of sugary foods. The activation of this region led participants to feel a desire for these foods.

Conclusion

This was a small human study that aimed to determine which areas of the brain were activated by the sight of food under different blood sugar levels. The use of both self-reported and brain imaging measurements provides information not only on physiological brain activity, but also on how this activity translates into consciously felt desires.

The researchers found that different areas of the brain are activated depending on the level of glucose available. When sufficient levels are present in the bloodstream, brain regions that control impulses seem to be activated. When low levels are present, brain regions that trigger desire and reward are more activated. The researchers say the level of activation of these regions differs depending on the weight of the individual.

When considering the implications of this research, it should be noted that the study was conducted under conditions that allowed the researchers to hold insulin levels constant artificially while manipulating glucose levels. This is not a state in which a person would find themselves naturally, as both insulin and glucose levels vary constantly. This feature of the study makes it difficult to generalise the results to a real world setting, particularly as, in everyday life, blood insulin levels would be expected to drop once sugar levels were too low.

This study has produced some interesting results but, ultimately, studies of this size are useful for generating theories rather than proving them. The sample size here (14 people) was very small and the results should be interpreted cautiously. Also, any comparisons between the obese and non-obese participants (five and nine people, respectively) are likely to be influenced by chance. Any further research attempts to confirm these results should involve more participants.

Links to the headlines

Why 'good' sugar is the secret to a slim figure. The Daily Telegraph, September 20 2011

The sweet science: Our uncontrollable cravings for treats are triggered by falls in blood sugar. Daily Mail, September 20 2011

Links to the science

Page KA, Seo D, Belfort-DeAguiar R et al. Circulating glucose levels modulate neural control of desire for high-calorie foods in humans.The Journal of Clinical Investigation, September 12 2011

Link between aspirin and eye condition unclear

reposted from:  http://www.nhs.uk/news/2011/10October/Pages/daily-aspirin-use-amd-vision-loss.aspx

crabsallover highlights, key points, comments / links.

“People who take a daily dose of aspirin are twice as likely to suffer blindness in later life,” The Daily Telegraph reported. The newspaper said that an international study of over 4,000 elderly people found that daily aspirin users are twice as likely to be diagnosed with a late-stage form of age-related macular degeneration(AMD), a common cause of vision problems in older people.

The study examined the association between aspirin use among older people and AMD. To examine the relationship, researchers tested the eyes of 4,691 adults aged over 65. They also assessed their aspirin use and other medical and lifestyle factors. The researchers found that people who took aspirin daily were more than twice as likely to have a more severe, later stage of AMD. This is known as “wet” AMD, and about 15% of people with AMD develop it. However, the relationship between aspirin use and other stages of AMD was not consistent, with aspirin users being no more likely to have mid-stage AMD.

As this study assessed AMD and aspirin use at the same time, it cannot show that regular aspirin use causes or increases the risk of vision problems. As such, we cannot tell whether aspirin use or vision problems came first. On the evidence provided by this particular study, it is not possible to tell how or whether the two are related, or if some unaccounted for factor is linked to both aspirin use and AMD. For example, aspirin is often prescribed to people with cardiovascular problems, which are themselves associated with smoking and obesity. Both of these are risk factors for AMD.

However, the study does raise questions about whether there could be an association between AMD and regular aspirin use, and the subject warrants further investigation.

Where did the story come from?

The study was carried out by researchers from a number of European centres, including Queen’s University, Belfast, and the London School of Hygiene and Tropical Medicine. It was funded by several organisations including the EU and the Macular Disease Society UK. The study was published in Ophthalmology,the peer-reviewed journal of the American Academy of Ophthalmology.

While headlines tended to overstate the certainty of the study’s findings, both the Daily Mail and the Telegraph pointed out that the study provided no evidence that aspirin use itself caused the participants’ AMD. The newspapers also explained that the relationship may be due to confounding factors. For example, it is possible that AMD was caused by cardiovascular disease, which might typically be treated using aspirin.

Some reports suggested that aspirin use was associated with “blindness”, but this may not reflect the nature of AMD. For example, the degree of visual impairment experienced by people with AMD can vary, and people may have distorted vision rather than no vision at all. Although it can cause severe visual impairment as central vision is lost (affecting everyday activities such as reading and writing), it does not usually affect peripheral vision and generally does not cause profound blindness.

What kind of research was this?

This cross-sectional study of nearly 4,700 older people explored the possible association between use of aspirin and the development of age-related macular degeneration (AMD). This type of study can provide a “snapshot” of health-related issues in a particular population at a certain point in time, but it cannot show cause and effect.

AMD (referred to in the research paper as aging macular disorder) is the most common cause of vision loss in people over 50. It occurs when problems affect the workings of the macula, the spot on the back of the eye that is responsible for central vision. This leads to a gradual loss of central vision, which is needed for detailed work and for tasks like driving or reading. However, it does not normally lead to complete blindness.

There are two main types of AMD, called wet and dry AMD. Dry AMD is the most common form. It usually progresses in stages causing gradual loss of vision over time. About 15% of people with AMD develop wet AMD. It is called wet because it is associated with the growth of abnormal new blood vessels in the retina, which are fragile and prone to bleeding.

The researchers say that while previous research has explored an association between aspirin use and AMD, findings have so far been inconsistent.

What did the research involve?

Between 2000 and 2003, researchers recruited participants aged 65 or over by randomly sampling people from national population registers of seven European countries. Participants were interviewed and given a structured questionnaire. This asked about their aspirin intake and other factors such as socioeconomic background, medical history, smoking and alcohol consumption. Aspirin intake was split into four categories ranging from “never” to “daily use”. Researchers also took into account other health measures, such a body mass index, blood pressure and cholesterol levels.

Participants underwent standard ophthalmic tests for AMD, with their AMD progression graded using a five-stage scale. A score of 0 indicated no AMD and the last stage – stage 4 – was also classified as being either dry or wet (not everyone with late-stage AMD will progress to the wet form). The classification system they used is a recognised international grading system.

The researchers then used standard statistical methods to analyse any association between aspirin use and AMD.

What were the basic results?

Of the initial 4,753 participants, the researchers excluded 62 for whom information on aspirin use was missing. This left 4,691 participants. They found that 36.4% (1,706) had early AMD (stages 0–3) and 3.3% (157) had late AMD (stage 4). Of those with stage 4 AMD, 108 had the wet form and 49 the dry form.

Within the whole study population, 41.2% took aspirin once a month, 7% at least once a week and 17.3% took aspirin daily.

After the researchers had adjusted for potential confounders, they calculated the associations between daily aspirin use and each grade of AMD. They found that there was:

• a 26% increased risk of grade 1 AMD (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.08–1.46)
• a 42% increased risk of grade 2 AMD (OR 1.42, 95% CI 1.18–1.70)
• no increased risk of grade 3 AMD
• a more than double risk of grade 4 wet AMD (OR 2.22, 95% CI 1.61–3.05)
• no increased risk of grade 4 dry AMD

How did the researchers interpret the results?

The researchers say that frequent aspirin use was associated with early AMD and wet late AMD. The risk rose with increasing frequency of aspirin use. They consider that, as aspirin acts on the body in several ways, it is possible that it affects blood vessels in the eye. However, further study of this is needed.

Conclusion

This large study had strengths, including the fact that it took a random sample of the population and established the presence of AMD using validated methods and accepted grading procedures for AMD. The researchers also tried to take account of other factors that could have affected the risk of AMD, in particular cardiovascular disease, smoking and excess weight, which are known risk factors for AMD.

The study’s major limitation is its cross-sectional design, which means it cannot establish cause and effect. As such, while the study has shown associations between aspirin use and vision problems, it cannot tell how or whether the two are directly related, nor which came first. While we could speculate that aspirin somehow causes AMD, it could also be suggested that AMD might be the result of cardiovascular conditions that require treatment with aspirin. Also, although the researchers attempted to adjust their analyses for confounders – including those known to be associated with AMD – other factors may be independently related to both aspirin use and AMD and could account for the observed relationship.

The relationship was also not completely consistent. Aspirin use was not associated with grade 3 AMD or grade 4 dry AMD. This suggests that the findings could possibly have happened by chance.

The limitations of the study’s design, together with the inconsistent results of other studies on the matter, mean it is hard to tell if there truly is an association between regular aspirin use and AMD. However, the possibility of an association seems worthy of further exploration. Ideally, this would involve examining people’s eyes to check they do not have AMD and following them over time to see whether people taking aspirin daily are more likely to develop the condition in the future.

Links to the headlines

Regular aspirin users at higher risk of sight problems, research suggests. The Daily Telegraph, October 4 2011

Over-65s who take a daily aspirin are 'twice as likely to suffer age-related sight loss'. Daily Mail, October 4 2011

Links to the science

de Jong PTVM, Chakravarthy U, Rahu M. Associations between Aspirin Use and Aging Macula Disorder. Ophthalmology, September 14 2011 (published online)

Reactive oxygen species (ROS) damage internal cell structure

reposted from: http://www.nhs.uk/news/2011/11November/Pages/common-drug-may-slow-progeria.aspx

crabsallover highlights, key points, comments / links.

NHS.uk say:-

New pill to halt ageing, papers claim

NHS Choices Wed Nov 2, 2011 15:52 Share

Scientists may have “found a cure for ageing”, the Daily Mirror reported. According to the newspaper, the answer could lie in a “forever young” drug that will allow us to grow old gracefully.

However, this seeminly marvelous news is based on a small study which looked at an extremely rare form of a genetic condition called progeria. This causes children’s bodies to rapidly age and leads to a number of physical health problems, limiting their lifespan to an average of around 13 years.

The researchers examined the cells of people with the condition and found that, compared to cells from healthy individuals, they produced five times the level of ‘reactive oxygen species’ (ROS), chemicals that are damaging to the internal cell structure. These higher ROS levels were associated with more breaks in the cells’ DNA and abnormal cell growth. However, when the cells were treated with a drug called N-acetylcysteine, which is already used to prevent liver damage in people who have overdosed on paracetamol, the researchers were able to largely prevent this DNA damage and improve cell growth and division.

The findings of this study are at a very early stage and suggest some potential ways to help people with rare but devastating forms of progeria. However, it is too great a leap too suggest that the research provides a “cure for ageing”, as some fanciful reports have done.

Where did the story come from?

The study was carried out by researchers from Durham University and the University of Bologna in Italy. It was funded by the European Commission and published in the peer-reviewed scientific journal Human Molecular Genetics.

Most news coverage on the research suggested that it could offer a way to slow or even stop routine human ageing. However, the media’s outlandish claims that scientists are on the verge of a “forever young drug” or a “cure for ageing” are not supported by this research.

Several newspapers focussed on the fact that the study used an existing drug called N-acetylcysteine, and implied that it could soon be used to block the effects of ageing. The drug is currently an ingredient in some eye drops and also has a role in treating paracetamol overdoses and poisoning, for which it is given intravenously for short periods. While it has been proven safe and effective for these uses, there are no guarantees that it would be safe or effective if taken orally in the long term.

Only the BBC’s coverage primarily focussed on progeria, the rare rapid-ageing condition that the research examined.

What kind of research was this?

This study was a laboratory-based investigation into the cause of and possible solutions to the genetic damage that occurs in a group of inherited degenerative disorders called laminopathies. These conditions are caused by mutations in a gene called LMNA, which normally produces a protein called lamin A. The lamin A protein plays an important role in keeping the structures within cells strong and stable.

The study focused on the most severe group of laminopathies, including the rare Hutchinson Gilford progeria syndrome (HGPS), which causes children’s bodies to age too quickly. This causes a range of effects, including restricting growth and loss of body fat and hair. Children with HGPS develop heart disease early in life, and have an average life expectancy of just 13 years.

Laboratory studies are the best way to determine exactly what happens in the individual cells of people with these types of genetic conditions. The results can help researchers explain the symptoms that people develop.

...

Previous studies have shown that skin cells from these patients have high levels of chemicals called reactive oxygen species (ROS). ROS can cause double strand breaks in DNA, and are thought to be involved in the accumulation of this type of DNA damage in normal ageing cells. Therefore, the researchers wanted to test whether ROS might be responsible for the DNA damage seen in cells from patients with laminopathies.

The researchers first compared the level of ROS produced by the cells, and then compared the level of damage caused by ROS in the cells. Specifically, they looked at how ROS caused DNA damage and disruption in the shape of the cells’ internal structures.

Finally, they investigated whether a drug called N-acetylcysteine could reduce the damaging effect of the ROS in the healthy and diseased cells. N-acetylcysteine is a chemical that “mops up” the damaging ROS and is already used to prevent liver damage in patients who have overdosed on paracetamol.

What were the basic results?

The researchers found that:

• The cells from people with HGPS had ROS levels that were five times higher than those from healthy individuals.
• The high ROS levels were linked to DNA damage (due to double strand breaks in the DNA).
• The accumulation of DNA damage in these fibroblasts appeared to cause poor cell growth.
• ROS-induced DNA damage could be repaired efficiently in cells from healthy individuals, but could not be repaired in the cells from people with HGPS.
• Adding N-acetylcysteine to the cells of HGPS patients led to a significant increase their ability to grow and multiply. The cells also did not develop un-repairable ROS-induced DNA damage.

How did the researchers interpret the results?

The researchers say their findings suggest that the accumulation of ROS-induced DNA damage can “contribute significantly” to the problems seen in the cells of people with HGPS. They also state that N-acetylcysteine in combination with other treatments “might prove beneficial to HGPS patients”.

Conclusion

This laboratory-based study of isolated human cells provides interesting new evidence on how reactive oxygen species (ROS) potentially causes DNA damage in the accelerated ageing condition Hutchinson Gilford progeria syndrome (HGPS). It also highlights that N-acetylcysteine might be of use in treating patients with HGPS.

While this study provides interesting new findings, the following limitations should be considered:

• This study experimented on isolated human cells in a laboratory, and it is not known what the effect of N-acetylcysteine would be if it was given to children with the illness.
• This is early-stage research, the results of which will need to be confirmed in future studies. The effectiveness and safety of N-acetylcysteine is likely to need to be tested in animal models of the condition before it could be tested in people. However, the fact that N–acetylcysteine is already used as a treatment for paracetamol overdose may mean that human trials could be carried out sooner than for a completely new drug. That said, it would still need to be tested, particular its effects when taken in the long term.
• A full randomised clinical trial of N-acetylcysteine may be difficult to conduct as the condition is so rare. The Progeria Research Foundation says that just 78 children are known to have the condition.
• The newspapers suggest that the findings are applicable to normal ageing, and that N-acetylcysteine could be a “cure for ageing”. This study focussed on the effect of N-acetylcysteine on the cells of patients with HGPS, a rare, severe genetic condition. It is not possible to say from this study how the findings would apply to the normal ageing process.
• HGPS is a genetic condition, and although N-acetylcysteine might be able to reduce or block some of the damage seen in the cells of people with HGPS, it will not remove the genetic mutation itself or allow the body to produce the important lamin A protein.
• Regular cellular and physical ageing involves a complex mix of mechanisms. Even if N-acetylcysteine can block some of them, this does not mean that it could stop or greatly slow the overall ageing process.

These findings are at a very early stage and will aid further research into HGPS. However, it may take many years to confirm these findings through other studies and to assess the effects of N-acetylcysteine in HGPS patients. The implications of these findings for the ageing process of people without HGPS is unclear, and it is certainly too early to say that an “ageing pill” is just around the corner.

Links To The Headlines

Progeria may be treated by drug, researchers say. BBC News, November 2 2011

Breakthrough could lead to treatment for symptoms of growing old. The Daily Telegraph, November 2 2011

Scientists "find cure for ageing". Daily Mail, November 2 2011

Pill 'to combat ageing'. The Sun, November 2 2011

'Forever young' drug that lets you grow old gracefully could soon be reality. Daily Mail, November 2 2011

Links To Science

Richards SA, Muter J, Ritchie P et al. The accumulation of un-repairable DNA damage in laminopathy progeria fibroblasts is caused by ROS generation and is prevented by treatment with N-acetyl cysteine. Human Molecular Genetics, 2011 20 (20): 3997-4004