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last updated: Sun, 26 Mar 2017 16:41:33 GMT

 Fri, 24 Mar 2017 17:30:00 GMT Modified protein promotes hair growth and fights ageing in mice

"Scientists create a chemical that can restore hair and give youthful energy," the Daily Mail reports; but these effects have only been achieved in mice. A modified protein called FOXO4-DRI has been successfully used to remove "broken ageing" cells.

The new study was looking at what are known as senescent cells. These are cells that have "aged" in that they have stopped dividing. Senescent cells are thought to contribute to both the ageing process in general, as well as age-related diseases, such as arthritis.

Researchers investigated whether a modified version of a protein called FOXO4-DRI was able to "seek and destroy" senescent cells from mice, in the hope this may counteract signs of ageing.

Researchers used naturally ageing mice as well as mice genetically modified to age more rapidly. They exposed both sets of mice to toxic chemotherapy drugs to place additional stress on their cellular functions.

They found FOXO4-DRI was able to neutralise toxicity caused by chemotherapy in the rapidly ageing and naturally ageing mice. It was also able to counteract loss of liver and kidney function, frailty and loss of fur density in the mice.

This is very early stage animal research and further studies are needed before FOXO4-DRI can be tested in humans.

It is likely that further research on FOXO4-DRI will be carried out, as a drug that could treat both hair loss and reverse some of the effects of ageing would have considerable commercial potential.

 

Where did the story come from?

The study was carried out by researchers from several institutions in the Netherlands, Austria and the US, including, Erasmus University Medical Center Rotterdam and the Buck Institute for Research on Aging, California. It was funded by grants from the NIH and NIA, the Austrian Science Fund, and the Royal Netherlands Academy of Arts and Sciences.

The study was published in the peer-reviewed scientific journal Cell. It is available on an open-access basis and is free to read online.

Generally, the media coverage on this study was well balanced – especially by BBC Online. The Mail was perhaps a little over-optimistic with its headline claiming the compound would "restore hair and give youthful energy." Though it did eventually go on to mention that this was a mouse study.

Coincidentally, this anti-ageing research in mice study was published the same time as another anti-ageing research in mice study (published in the journal Science).  

What kind of research was this?

This was an animal study which investigated whether targeting senescent cells – cells that have stopped dividing – could counteract damage to tissue in the body caused by medical treatments such as chemotherapy, as well as by ageing.

Senescent cells have been observed to impair tissue function, and are able to avoid apoptosis – the process of cell death – and as a result, continue to live on in the body for long periods of time. While cell death may sound like a bad thing, apoptosis actually results in the removal of unhealthy, aged cells.

The researchers wanted to explore whether there are ways in which senescent cells can be flushed from the body to reduce the impact of ageing.

In particular, they wanted to see if the use of cell-penetrating peptides (CPPs) would contribute to this. CPPs are able to block interactions between proteins. The researchers hoped that these could be used to target senescent cells.

Mice studies like this one are useful early stage research which can allow scientists to better understand the complex chemical interactions that take place in cells. However, further research is needed to see if these same effects will be observed in humans. The researchers based in The Netherlands plan to run human trials to explore their findings.

The first stage is likely to be a phase I trial, which are small trials used to assess whether a new drug is safe to use.

 

What did the research involve?

The research involved cells from naturally ageing mice and those genetically engineered to age rapidly. Cells were induced to senesce by ionising radiation or by the chemotherapy drug doxorubicin. They investigated whether apoptosis (cell death) pathways are different within these senescing cells, and tested whether different cell-penetrating peptides (CPPs) could alter these pathways and counteract the process of senescence.

While testing the effects of one CPP in particular, FOXO4, the researchers found that by modifying the peptide they could give it new properties. They tested the effects of the modified peptide, (called FOXO4-DRI), on senescing cells.

The mice were given FOXO4-DRI three times a week for 10 months, and their activity on a running wheel was tested over four days. Changes in fur density were also measured.

 

What were the basic results?

The researchers found that the CPP, FOXO4 when modified to FOXO4-DRI, has the capability to modulate the apoptosis-pathway in senescent cells. It worked by disrupting the interaction between FOXO4 and the tumour protein p53. This interruption causes apoptosis to take place within senescent cells, therefore causing cell death.

When it was well tolerated, FOXO4-DRI was able to neutralise toxicity caused by chemotherapy in both the rapidly ageing and naturally ageing mice. It was also able to counteract loss of liver and kidney function, frailty (as indicated by increased running activity) and loss of fur density in the mice.

 

How did the researchers interpret the results?

The researchers concluded: "Therapeutic targeting of senescent cells is feasible under conditions where loss of health has already occurred, and in doing so tissue homeostasis can effectively be restored."

"In any case, the here reported beneficial effects of FOXO4-DRI provide a wide range of possibilities for studying the potential of therapeutic removal of senescence against diseases for which few options are available."

 

Conclusion

This mouse study aimed to investigate whether there are ways to target and destroy senescent cells that have stopped dividing yet somehow avoid the normal cell-death pathways. Removing these cells could counteract damage to tissue in the body caused by medical treatments such as chemotherapy, and accelerated or natural ageing.

It essentially found that a modified peptide (FOXO4-DRI) was able to cause death of the senescent cells. In turn, this was able to counteract the liver and kidney cell toxicity induced by a chemotherapy drug, in addition to reducing frailty and loss of fur density in the mice.

Animal studies such as this are very early stage research, useful for better understanding the complex mechanisms that take place at a cellular level. However, further research is needed before this can be tested in humans.

Humans are not identical to mice therefore we don't know whether the biological effects would be the same.

Mice studies are able to give very little indication of the potential adverse side effects that such treatments might cause, or look into the long term implications. As one of the lead researchers succinctly put it about the limitations of using mice – "mice don't talk".

It is certainly far too early to suggest this as a potential anti-ageing treatment for humans, or a treatment to counteract the side effects of chemotherapy or radiotherapy.

Dr. Dusko Ilic (who was not involved in the study) from King's College London told the BBC: "The finding is impossible to dismiss. [But] until more high-quality research is done, it is better to be reserved about these findings."

Links To The Headlines

The anti-ageing compound: Scientists create a chemical that can restore hair and give youthful energy. Daily Mail, March 24 2017

Drug 'reverses' ageing in animal tests. BBC News, March 23 2017

Links To Science

Baar MP, Brandt RMC, Putavet DA, et al. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. Published online March 23 2017

 Thu, 23 Mar 2017 17:30:00 GMT Moderate drinking may reduce heart disease risk

"A daily pint or glass of wine can slash the chances of a suffering heart attack by a third," reports The Sun.

Researchers found that people who drank alcohol within moderate drinking guidelines were less likely to have a first episode of a range of heart and vascular diseases than those who never drank alcohol.

This four-year study looked at health records of almost 2 million adults without any cardiovascular disease at the start of the study.

It found that non-drinkers were more likely to need treatment for many diseases such as heart attack, heart failure and angina, compared to people who drank alcohol within the previous recommended guidelines, which were 21 units per week for men and 14 units for women.

There was less difference between the groups for circulation diseases such as stroke and bleeding in the brain.

However, heavy drinkers, consuming above guideline limits, were also at higher risk compared with moderate drinkers. Former and occasional drinkers also had increased risk of several outcomes.

Along with other study limitations, like the possible influence of other health and lifestyle factors, we can't be certain that moderate drinking directly decreases risk.

And at the risk of sounding like killjoys, there are far healthier and more effective methods of reducing cardiovascular disease, such as regular exercise. Regular drinking, can increase your risks of a number of cancers.

Alcohol guidelines changed at the start of 2016 to recommend that both men and women should drink no more than 14 units per week. This was to reflect the point that there is no such thing as a "safe amount" of alcohol.

 

Where did the story come from?

The study was carried out by researchers from Cambridge University and University College London and was funded by organisations including the National Institute for Health Research, Wellcome Trust and Medical Research Council.

The study was published in the peer-reviewed British Medical Journal (BMJ) on an open-access basis so it is free to read online.

The study was received with enthusiasm by the UK media. The Sun's exhortation to readers to drink "a pint a day," accompanied by a photograph of a man sinking a beer, was typical of the tone of much of the coverage. However, the headline oversimplifies the study.

The Daily Mirror does a more balanced job, warning readers that "There's a catch" and quoting experts warning of the link between alcohol and cancer.

The Mirror also carries a statement from Dave Roberts, director general of the Alcohol Information Partnership, who claims that "the anti-alcohol campaigners' mantra that there is no safe limit just doesn't stack up".

But as the Alcohol Information Partnership is funded by drinks firms including Diageo, Pernod Ricard, Campari and Bacardi (as the Mirror helpfully points out) there may be a potential conflict of interest.

The media reporting also fails to point out that this study was basing the definition of moderate drinking on the old, pre-2016, recommendations (21 units per week for a man, 14 per week for a woman).

 

What kind of research was this?

This was a cohort study using population-based records. Researchers wanted to see how alcohol consumption at different levels was linked to a wide range of cardiovascular conditions.

Cohort studies can show links between factors, such as alcohol consumption and cardiovascular disease risk. But they can't show that one factor causes another. Confounding factors (such as diet and physical activity) might distort the results.

 

What did the research involve?

Researchers used anonymised electronic patient records from a GP database, which included people's reported alcohol consumption. They included 1,937,360 patients aged 30 or over, and tracked their illnesses, hospital admissions and deaths over an average six years.

They divided people into groups based on their drinking, then (after adjusting for confounding factors) looked to see what their chances were of having had one of 12 cardiovascular conditions, or having died from any cause.

The researchers only looked at people's first record of a cardiovascular disease. So, for example, someone might have had treatment for unstable angina, then later go on to have a heart attack, but only the unstable angina would be recorded.

The researchers used three linked databases, to give them a better chance of including all necessary detail. As well as the GP database they used the Myocardial Ischaemia National Audit Registry Project, hospital episode statistics and the Office of National Statistics.

The researchers divided people into five groups: non-drinkers (who never drank alcohol), former drinkers, occasional drinkers, moderate drinkers (who drank within the then-current guidelines of 21 units per week for men and 14 units for women) and heavy drinkers (who exceeded this).

Potential confounding factors included in the analysis were:

  • age
  • sex
  • socioeconomic deprivation
  • smoking status
  • diabetes
  • blood pressure
  • body mass index (BMI)
  • cholesterol
  • use of antihypertensive or statin medicines
  • whether the patient had received dietary advice

 

What were the basic results?

About 5% of people in the study had a first diagnosis of a cardiovascular disease during the study. As in previous studies, this was more common among non-drinkers, former drinkers, occasional drinkers and heavy drinkers, compared to moderate drinkers.

Compared to moderate drinkers, non-drinkers had a higher risk of a first report of:

  • heart attack (32% higher risk, hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.24 to 1.41)
  • unexpected death from heart disease (56% higher risk, HR 1.56, 95% CI 1.38 to 1.76)
  • heart failure (24% higher risk, HR 1.24, 95% CI 1.11 to 1.38)
  • unstable angina (33% higher risk, HR 1.33, 95% CI 1.21 to 1.45)
  • stable angina (15% higher risk, HR 1.15, 95% CI 1.09 to 1.21)
  • stroke (12% higher risk, HR 1.12, 95% CI 1.01 to 1.24)
  • peripheral artery disease (22% increased risk, HR 1.22, 95% CI 1.13 to 1.32)
  • abdominal aortic aneurysm (32% increased risk, HR 1.32, 95% CI 1.17 to 1.49)
  • death from any cause (24% increased risk, HR 1.20 to 1.28)

There was no significantly increased risk of bleeding in the brain, transient ischaemic attack ("mini-stroke"), or sudden cardiac death.

Heavy drinkers also had an increased risk of death from any cause or from heart disease, of cardiac arrest, heart failure, stroke from blood clot or bleed and peripheral artery disease, with risk increases ranging between 11% and 50%.

Former drinkers and occasional drinks also had increased risk of most outcomes compared with moderate drinkers.

The researchers also noted that all non-drinkers were more likely to belong to the most deprived socioeconomic group, to have diabetes, and to be obese.

The results were similar for women, although there was less difference in risk levels between non-drinkers and moderate drinkers.

 

How did the researchers interpret the results?

The researchers say their study showed that "moderate alcohol consumption is associated with a lower risk of initially presenting with several, but not all, cardiovascular diseases." They go on to say that "heavy drinking is differentially associated with a range of diseases."

While the research found that heavy drinkers were less likely to have a heart attack as a first presentation, the researchers warn that could be because "they die from other causes before they are able to develop a cardiovascular disease."

 

Conclusion

This study paints a more complicated picture than the "Pint a day keeps the doctor away" story proffered by The Sun.

It seems to confirm the findings of other studies, which have shown that non-drinkers tend to have a higher risk of cardiovascular diseases than people who drink moderately.

It suggests that some cardiovascular diseases (mainly those directly affecting the heart) seem to have a stronger link to a possible protective effect from alcohol than other vascular diseases, such as mini-strokes and bleeding in the brain. However, this can't be concluded with certainty due to the study design.

We need to remember that cohort studies like this cannot prove that alcohol consumption or lack of it is a direct cause of cardiovascular disease. Many health and lifestyle factors may be having an influence. For example, non-drinkers were more likely to be from deprived areas, to have diabetes or be obese, factors which the analysis didn't adjust for.

We also have no information about other factors such as diet or exercise, which could also affect the results.

Also, the researchers' decision only to include people's first diagnosis of a cardiovascular disease complicates matters. For example, if a person had a Transient ischaemic attack (TIA) (also known as a "mini-stroke") and then went onto have a full stroke, only the TIA would be recorded. Therefore it is difficult to be certain of a person's overall cardiovascular disease status. We can't be sure that the figures around how much a person's risk of a particular disease outcome is increased by a particular consumption level are accurate.

As a result, we really shouldn't conclude, for example, that people who drink heavily are less likely to have a heart attack than those who don't drink. They may have a stroke first, and then a heart attack, or die of another cause.

The study isn't a green light for people to drink more alcohol, without worrying about it. However, it does suggest that drinking alcohol within the lower-risk drinking guidelines may not raise the risk of cardiovascular disease, and may lower it. Remember that alcohol does contribute to other diseases.

Check whether you're drinking within low-risk levels with our introduction to alcohol units.

Far more effective, safer, and usually cheaper, methods of reducing your heart disease risk include regular exercisehealthy eating and quitting smoking if you smoke.

Links To The Headlines

Reduce your chances of having a heart attack by a THIRD with a daily pint or glass of wine. The Sun, March 23 2017

An alcoholic tipple a day could PREVENT you having a heart attack - but there's a catch. Daily Mirror, March 23 2017

Moderate drinking can lower risk of heart attack, says study. The Guardian, March 23 2017

Cheers! Drinkers who have one glass of wine a night 'are at less risk of heart failure than teetotallers'. Mail Online, March 23 2017

Drinking pint of beer a day linked to reduced risk of heart attack. The Independent, March 23 2017

Moderate drinkers have lower risk of heart attack. The Times, March 23 2017 (subscription required)

Links To Science

Bell S, Daskalopoulou M, Rapsomanki E, et al. Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records. BMJ. Published online March 22 2017

 Thu, 23 Mar 2017 16:00:00 GMT Mixing alcohol and energy drinks 'may be a risky cocktail'

"Mixing energy drinks with alcohol could be a risky combination, leading to a greater risk of accidents and injuries," BBC News report.

A review of evidence found a number of potential risks, but the picture was not as clear-cut as reported.

Energy drinks are drinks that contain high amounts of caffeine. Some people mix them with spirits such as vodka.

Canadian researchers aimed to look at the published evidence on whether mixing alcohol with energy drinks is linked to an increased risk of harm or injury.

The researchers identified 13 studies – overall, 10 of them reported an increased risk of injury when drinking the mixture compared with alcohol on its own.

One possible factor discussed in the review is that the stimulant effects of caffeine could combine with the inhibition-lowering effects of alcohol, making people more prone to taking risks.

Caffeine could also mask the sedative effects of alcohol, so people become less aware of how much alcohol they've drunk – a phenomenon referred to as being "wide-awake drunk". 

However, the studies included in the review varied considerably in their methods, including the lifestyle factors they took into account, such as alcohol or drug use.

This review can't quantify risks or link them with particular combinations of drink, or specific quantities.

But it does serve as a general reminder that so-called "social drinking" is not without risk, both in terms of how much alcohol is consumed and potentially making yourself vulnerable to harm.

Where did the story come from?

The study was carried out by two researchers from the Centre for Addictions Research at the University of Victoria in British Columbia, Canada.

It was funded by the Canadian Institute of Health Research. No conflicts of interest were reported by the researchers.

The study was published in the peer-reviewed Journal of Studies on Alcohol and Drugs on an open access basis, so it's free to read the study online (PDF, 208kb).

The way the study was reported, while generally accurate, in some cases made the links between risks and drinking alcohol combined with energy drinks appear to be much better established than is actually the case.

And The Sun's headline, "Bingeing on vodka Red Bull or Jagerbombs 'as bad as taking cocaine'," is an opinion, not a proven fact. 

What kind of research was this?

This systematic review aimed to examine the published literature to identify studies that have assessed the link between mixing alcohol with energy drinks and the potential risk of injury. 

The researchers say in 2007-11, 13-16% of emergency department visits in North America involved people who had drunk alcohol combined with energy drinks.

This is said to be the first review to date to look at the association. A systematic review is the best way of compiling the available literature.

However, the findings of reviews are only as good as the pooled studies included.

Studies assessing links between food and drink and health outcomes are usually observational, so they aren't able to prove cause and effect because many other factors could have had an influence.

And if the studies included in a review are very different in terms of methodology, as was the case with this review, it isn't possible to carry out a meta-analysis of the results.

This means any conclusions provided by the review carry less weight of evidence.

What did the research involve?

The reviewers searched two literature databases to identify studies published between 1981 and January 2016.

The studies included must have looked at the link between consuming alcohol mixed with energy drinks and the risk of harm or injury, and compared this with the risk from just drinking alcohol.

Energy drinks and alcohol could be either consumed in a mixed drink or separately, but on the same occasion.

A total of 13 studies met the inclusion criteria – 10 of which came from the US and Canada, and the remainder from New Zealand, Australia and Taiwan.

Eight of the studies included students – high school, college or university. They all date from 2011-15.

All of the studies were cross-sectional, mostly online surveys reviewing reports of drinking injuries.

The timeframe of alcohol or energy drink consumption was questioned ranged from the past month to the past year, while the timeframe for self-reported injuries ranged from the past month to a lifetime.

Eight of the studies asked whether injuries were actually related to drink consumption, while the other five studies just asked about reports of the two, which may not necessarily have been related.

What were the basic results?

The reviewers give an overall narrative summary of the findings.

Ten of the 13 studies reported a link between drinking alcohol and energy drinks and an increased risk of injury, though there were no consistent links with the type of injury.

Three studies didn't find this link – in fact, one study actually found the risk was higher with alcohol on its own. The researchers feel the differences could have been down to the design of the studies.

Three studies reported that when the links between the two are assessed, you need to consider risk-taking tendencies or behaviours, as well as sensation seeking.

When the researchers controlled for these variables, they still found links between alcohol and energy drinks and injury.

Most studies also controlled for general alcohol consumption or binge drinking. Two studies also controlled for drug use and one for caffeine.

Studies also reported more alcohol tended to be consumed during mixed drinking sessions than when drinking alcohol on its own.

How did the researchers interpret the results?

The researchers concluded: "There is significant need for further examination of the role of [alcohol and energy drink] use in the risk of injury.

"A better understanding of the relationship … and of the potential underlying mechanisms is crucial for informing effective preventive intervention strategies."

They go on to say the review could be used to inform the public, health professionals and policy makers of the possible risks.

Conclusion

This systematic review aimed to try to better establish whether drinking alcohol mixed with energy drinks is linked with risk of injury.

Although the majority of studies generally supported a link between consumption and increased risk of injury, as the researchers acknowledge, the high variability in the methods of the individual studies and assessment of harms "makes it difficult to determine the extent of this risk".

Nearly all the studies were online surveys that asked questions about alcohol and energy drink consumption, and self-reported injury.

But the temporal relationship between the two, and whether the drink was actually the direct cause of the reported injury, is very difficult to be sure of, especially if the timeframe of reported injuries could extend to up to a lifetime, while drink consumption was relatively recent.

For example, one of the studies was even questioning reports of injury or disease in the past year as a result of participants' work.

It's also possible confounding lifestyle factors influenced any links seen. The individual studies varied considerably in the different factors they adjusted for, such as socioeconomic factors, drug use, and normal alcohol drinking behaviours.  

The studies are also mostly representative of young student populations, and none were conducted in the UK. A link may be found if college or university students in the UK were surveyed, but we can't know this for sure.

Overall, although this study is of interest and supports a plausible theory, it can't definitively tell us whether drinking alcohol combined with energy drinks will put you at greater risk of injury or harm than if you drink alcohol alone.

But the study does reinforce the fact alcohol can be a common contributing factor to injury.

Read more about the risks associated with social drinking

Links To The Headlines

'Wide awake drunk' on energy drinks and alcohol mix. BBC News, March 21 2017

Mixing alcohol and energy drinks can make nights out more dangerous, researchers warn. The Independent, March 21 2017

Bingeing on vodka Red Bull or Jagerbombs 'as bad as taking cocaine' because it masks tiredness, experts warn. The Sun, March 21 2017

Links To Science

Roemer A, Stockwell T, et al. Alcohol Mixed With Energy Drinks and Risk of Injury: A Systematic Review. Journal of Studies on Alcohol and Drugs. Published online March 21 2017


 

 
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