Thursday, 23 February 2012

Old fruit flies and broken body clocks

Sleeping problems can get worse with age but they are often exacerabated in age-related diseases that involve damage to the brain such as Alzheimer's, Parkinson's and Huntingtons Disease [1]. Why does the body clock get disrupted? Indeed, is a disrupted body clock the result or the cause of these diseases, or a bit of both? Could a fully-working healthy body clock protect against these brain diseases?

A recent study in fruit flies being published next month aimed to address some of these questions [2]. The fruit fly has a body clock with behavioural rhythms and many similar genes to the human body clock. They also can suffer brain related ageing diseases, and as they typically only live for 2-3 months it doesn't take too long for researchers to study these.

Fruit flies (Drosophila Melanogaster) who live for 2-3 months are being used to study the effect of the body clock on age related diseases (C) Marcos Teixeira de Freitas

The researchers have certain fruit flies where a specific gene known to act in protecting the brain is removed, these flies die younger due to brain defects. They also have flies that don't have a functional body clock, these are lacking a gene called "period" and causes the fly to have no body clock rhythms, in gene expression or in behaviour.

They wanted to determine the effect the body clock has in protecting the brain from age-related diseases. Therefore they took their mutant flies that suffer age-related brain damage and bred them with the flies that have no body clock. 

What they saw was that if you take away the body clock from a fly that has age-related brain damage, they die even younger. So a functional body clock is being protective against these age-related brain diseases. 

Fruit flies that are prone to old age brain disease are more likely to die younger if their body clock is disrupted.   Adapted from Krishnan, 2012

To rule out any effects of the gene "period" working in another way other than to maintain a healthy body clock they also tested the effects of raising the age-related brain defect mutant fruit flies in constant light. Constant light also stops behavioural rhythms and the molecular body clock.

Stopping the body clock with constant light also caused the brain damage to be worse, so it wasn't due to other functions of the period gene.

This research doesn't fully resolve the question of the cause or effect of a disrupted body clock in age-related brain diseases, though it does suggest it to cause the brain damage to be worse.

However, the results do show how maintaining a healthy body clock can increase chances of survival in animals prone to age-related brain diseases. My hope is that research in this field will further our understanding of human ageing.

Enjoyed this post? Check out Young or old: who can stay awake better at the wheel? and Around the Clock Doc

[1] Vitiello, M. V. "Sleep and Circadian Rhythm Disorders in Human Aging and Dementia", Encyclopedia of Neuroscience, Pages 887–893

[2] Krishnan, N., et al., "Loss of circadian clock accelerates aging in neurodegeneration-prone mutants", Neurobiology of Disease, Vol 45, Issue 3, March 2012, Pages 1129–1135, doi:10.1016/j.nbd.2011.12.034

Thursday, 16 February 2012

Young or old: who can stay awake better at the wheel?

Following on from my blog post last week, I looked at other research on driving being published by researchers at Loughborough University. Their second paper this year has looked at who could cope better with boring afternoon driving after a bad night's sleep, old men or young men [1]

I realize this is going to be a controversial topic, comparing driving abilities of old and young men, and the results may (or may not) be surprising. The aim of the researchers is to improve information given to drivers, and not (that I am aware of) to influence insurance companies.

Why do this study on male drivers? In the UK 90% of sleep-related accidents involve male drivers. Most afternoon sleep-related accidents involve older drivers, are they more prone to fall asleep at this time of day and therefore need specific advice to avoid these accidents?

Men from two age categories were selected; young 20-26 years old, and old 52-74 years old. All were experienced drivers, driving for more than 3 hours each week for at least the past 2 years. The drivers came in to the lab twice: after a normal night's sleep, and two weeks apart after a restricted to 5 hours sleep.

Drivers drove for a montonous 2 hours in a simulator like the one above (C) Alan in Belfast

This time they all had a light lunch before starting their 2 hour monotonous drive in the simulator. Drivers stayed in the left hand lane, at a steady speed, occasionally overtaking. Whenever the driver drove onto the "rumble strip" on the hard shoulder an "incident" was recorded. EEG (brain activity) and eye movement were monitored to determine when this lack of concentration was due to sleep, as opposed to being distracted. Drivers themselves were also monitoring how sleepy they felt.

The results showed that in fact younger drivers were more prone to having sleep-related incidents than old men at this time of day. This becomes significant after 30 minutes of driving and remained significant for the rest of the test. Young men were also more sleepy than the older men, from both their EEG patterns and their self-reports.

Young drivers were more prone to sleep-related lane crossing than older drivers
 in monotonous afternoon  driving after a short night's sleep. Adapted from Filtness, 2012

So are older men in fact better at driving when tired? This conclusion would agree with many other studies done looking at night time driving in different age groups [2]. Young men have more incidents during night time simulator driving and this corresponds with the road statistics  (I did lose an argument with my University professor trying to counter this, he had more data on his side).

Encouragingly, both groups were able to accurately rate their sleepiness, which correlated well with the EEG measurements. The older group were slightly better at this then the younger men, but both groups did realise they were sleepy.

So why are older men more likely to have an accident on the road in the afternoon? The data shows they are better able to cope with being sleepy. Unfortunately there are no statistics to show the percentage of different age groups on the road at different times of day, only those who are in accidents, so one possibility is there are just more older men on the roads in the afternoon.

The one flaw to this study is that using a simulator might not be as accurate as on the road, as the simulator may exaggerate any sleep related incidents, as there is no real risk to the driver. However, it would be unethical to do this test scientifically with drivers on the road.

Overall, this is an excellent study to address what is causing the sleep-related accidents on the roads. It really highlights the need for researchers to record driving effects for longer than 30 minutes. For advice on driving and when to take breaks and naps, please check out their website Awake.

Enjoyed this blog post? Check out Poor Sleep and a Large Lunch Effects Driving and Red Sky at Night, Sleepers Delight

[1] Filtness, A.J., Reyner, L.A., & Horne, J.A., Driver sleepiness—Comparisons between young and older men during a monotonous afternoon simulated drive. Biol. Psychol. (2012), doi:10.1016/j.biopsycho.2012.01.002

[2] Campagne, A., Pebayle, T., Muzet, A., 2004. Correlation between driving errors and vigilance level: influence of the driver’s age. Physiology & Behavior 80, 515–524

Tuesday, 14 February 2012

Happy Valentine's

Yesterday a friend asked me whether I was going to blog about Valentine's Day, well I wouldn't like to lose my reputation of being able to link body clocks to absolutely everything (they are pretty universal). So, I pondered whether there could be a good biological reason to celebrate Valentine's Day in February.

I first looked in the Body Clock Guide which has a whole chapter dedicated to the best times to make love. One study in it looked at the love lives of 5 Parisian men in the 1970's [1]. They examined the levels of testosterone and other hormones as well as activity for 14 months.

During October there was a rise in testosterone corresponding to love making activity, which then dipped over 6 months. So maybe, Valentine's Day is just what we need in February!

A young couple in love in Paris (C) Simon Moore, 2007

Many of the other studies looking at the best time of day to make love but on the whole have been limited by small number of participants and accuracy. There's not been many recent studies, so I presume it's quite hard to get scientific funding for these trials. However, the results tend to show peak times of day are when it's most convenient, between 10pm-1am being most popular.

Perhaps more accurate data will come out of apps like Mappiness, where you can state making love as an activity option when it beeps you to find out where and how happy you are.

Happy Valentine's Day!

[1] Reinberg, 1978, "Circadian and circannual rhythms in sexual activity and plasma hormones (FSH, LH, Testosterone) of five human males" Archives of Sexual Behavior Vol 7, No. 1, pg 13-30, DOI: 10.1007/BF01541895

Thursday, 9 February 2012

Poor sleep and a large lunch increases risk of a car accident

There's a lot of anecdotal evidence that would suggest that if you've had a bad night's sleep and you've got an afternoon full of boring dual carriageway driving ahead of you, it's probably not the best idea to have a large lunch. Well now there is the scientific data to prove it.

Researchers at The Sleep Research Centre at Loughborough University have recently published their results looking at the effect of eating a large lunch on afternoon driving ability [1]. It is the first of it's kind to look at long montonous driving in the lab. Most studies have only analysed the first 20 minutes and others were limited by examining non-driving skills such as psychologocial performance tests, which have come up with confusing results.

Experienced drivers who normally sleep well were recruited to perform monotonous afternoon driving in a simulator. In the simulator the drivers had to stay in the left hand lane, at a steady speed and would occasionally have to overtake slow drivers, to avoid collision. They were asked to drive for 2 hours without taking a break, the maximum time advised by UK road safety organisations.
Monotonous afternoon driving on a dual carriageway was simulated to look for
incidents of sleep-related lane deviations (C) fras1977, 2009
The study aimed to find out when they were falling asleep at the wheel. This can happen for seconds without the driver knowing they are falling asleep. Whenever the driver drove onto the "rumble strip" on the hard shoulder an "incident" was recorded. EEG (brain activity) and eye movement were monitored to determine when this lack of concentration was due to sleep, as opposed to being distracted.

The drivers were required to sleep well for 3 days and then the night before the experiment to restrict their sleep to 5 hours. Coming into the lab they were given lasagne and a yogurt, either a calorific meal or a light lunch. Both looked the same, in the same packaging, but one was 922 calories with lots of fats and carbs whilst the other was only 305 calories, and the subject didn't know which one they were eating. Then they were then sat down to drive for 2 hours in the driving simulator.

After 30 minutes of driving there was no difference between the number of "incidents" (driving on to the rumble strip due to drifting off to sleep). However at all times between 30 min - 2 hours of driving those who'd had the heavy meal were drifting off the road more.

The number of "incidents" (driving out of lane due to sleep) is increased in those who have had
a heavy lunch, EEG also shows their increased sleepiness. Adapted from Reyner, 2012

So this confirms what common sense would dictate, eating a heavy lunch after a bad night's sleep damages your ability to drive safely for long montonous car journeys in the afternoon. However, this was still an important study to perform.

The results of this experiment will improve the advice given to road users. Further information about their research, advice and services can be found at here. And, if you were concerned about whether the drivers got home safely after falling asleep in the simulator, don't worry, they were all taken home in a taxi.

[1] Reyner, L.S., Wells, S.J., Mortlock, V., & Horne, J.A. (2012). “Post-lunch” sleepiness during prolonged, monotonous driving - Effects of meal size. Physiology & behavior, 105(4), 1088-91. Elsevier Inc. doi:10.1016/j.physbeh.2011.11.025

Thursday, 2 February 2012

Using time of day to reduce heart damage in breast cancer treatment

A new paper this month suggests that treating breast cancer patients with radiation outside of the hours of 6am to noon will reduce side effects that could damage their heart [1].

Radiotherapy treatment has already been improving rapidly in many ways, to ensure that the tumour recieves the correct dose of treatment, whilst sparing the normal healthy tissue. However, radiation still carries an immediate and a long term risk of damage to the heart. Dr Gupta and his colleagues at the Department of Radiation Oncology in the Tata Memorial Cancer Centre in India, suggest that the correct timing of radiation treatment could minimise these risks further.

Radiotherapy is a common treatment for breast cancer, however one side effect is heart damage (C) CANCERactive 2012
With the significant improval in survival rates of breast cancer patients it has become even more important to minimise any long term effects of radiotherapy. Currently, in England and Wales, more than 70% of women diagnosed with breast cancer will live for at least 10 years, and it is predicted that 64% will live for at least 20 years [2]. Critical coronary artery disease can occur 10-15 years after radiotherapy and so it is vital that these long term effects are analysed.

Oxygen demand in the heart muscle is higher in the morning (6am and noon) but the supply of oxygen is lower. Unsuprisingly, this corresponds to when most heart attacks occur and when the heart is most prone to injury. Many other biological functions are occurring at this time of day that puts the heart at risk to damage: blood pressure is rising, adrenaline and other neurotransmitters are increasing, and people are becoming more active, putting more demand on the heart.

Dr Gupta suggests by avoiding radiation therapy in the morning in breast cancer patients, especially those receiving treatment in the left side, they will avoid short term and long term damage to the heart.

However, most radiotherapy treatment is now precisely targeted to the breast tissue (some radiotherapy machines can be precise to sub-millimeter), and there is speculation as to whether the surrounding heart tissue is effected [3]. It should be highlighted that to date there has been no analysis of the incidence of heart problems in breast cancer patients with standardised timing of radiotherapy, and therefore this is currently still a hypothesis.

Robust trials are certainly needed to address this issue, but the hope is that by using circadian timing, the side of effects of cancer treatments can be minimised whilst still allowing the treatment to be effective in removing the cancer.

Please note, I'm not a medical doctor, if you have breast cancer then you can speak to your doctor about timing your treatment. The above article is talking about a medical hypothesis (an idea) that has yet to be tested. Many cancer patients also have a desynchronised body clock, which can make it hard to pinpoint the perfect time of day to give treatment, and different treatments might have different times of day when they are more effective/less harmful. I hope you find my blog posts helpful in explaining the latest research and research ideas. Feel free to add a comment and I will try and answer any of your questions.

[1] Gupta D et al. Cardioprotective radiotherapy: The circadian way. Med Hypotheses (2012), doi:10.1016/j.mehy.2011.12.009

[2] Cancer Research UK website, CancerHelp UK, Breast Cancer Statistics and Outlook, accessed on 28-1-2012

[3] Response to "Radiation for breast cancer ups heart disease risk", accessed on 28-1-2012