aging

Why the government should reimburse anti-aging drugs

Healthcare costs are skyrocketing. The reason: the population is aging, but the age of onset of chronic diseases, the healthy age expectancy, is declining slightly. As a result, the period during which people need medical care is on average getting longer. Isn't it smarter to stop the aging process yourself, instead of treating the symptoms?

Healthy life expectancy
Healthy life expectancy is defined as the number of years of life that an average member of the population (eg Dutch or Belgians) spends disease-free. The older people get, the more likely they are to develop a chronic illness, such as diabetes, heart complaints or cancer. As a result, the number of years of illness, and with it the costs of health care, explode. Where in 1980 men in the Netherlands became ill on average at the age of 60, and died at the age of 72 (12 years), the number of years of illness has now increased to 15 years (on a life expectancy of 80 years) (1): This trend will , and continue without any major changes. In short: if we want the quality of life of the elderly to remain good and health care costs manageable, it is wise to focus much more on the prevention of chronic diseases than at present.

The percentage of healthy years is decreasing.

 

Chronic diseases as symptoms of aging
Chronic diseases are much more common in old people than in young people. The reason is that our body ages. This manifests itself in changes in cells, tissues and organs. Telomeres, the ends of chromosomes, shorten. More and more cells therefore jump into 'sleep mode': they change into senescent cells. Our immune system is weakened. Communication between mitochondria and the cell nucleus becomes disrupted (2). Proteins lose their shape and clog cells.
Recent scientific research increasingly shows that typical diseases of old age, such as diabetes, cancer, dementia and rheumatism, are in fact just symptoms of these processes. If we can stop or even reverse these aging processes, we will prevent many of these diseases.

Do we already have effective anti-aging drugs?
Perhaps inadvertently we even have some effective anti-aging drugs in our hands, which are now used to treat aging diseases. Metformin, for example, is an effective drug for adult-onset diabetes. Now medical examinations showed something remarkable. The life expectancy of diabetic patients treated with metformin was found to be even higher than that of

the healthy control group (3). Incidentally, Metformin is not a harmless candy and has some side effects.
A cocktail of the anti-leukemia drug dasatinib and quercetin (a dietary supplement) has been shown to be effective in removing senescent cells in patients with advanced IPF (idiopathic pulmonary fibrosis), resulting in a much better

he condition (4). Dasatinib also has the necessary side effects.

Prevention is more pleasant and cheaper than expensive foster care
If we succeed in slowing down or even reversing the aging process through a sophisticated combination of medicines and nutritional supplements, many healthy years of life will be added. They need less use of nursing care or hospitals and can work longer if they wish. And most importantly: this greatly increases the happiness of the elderly. If the government or health insurance companies reimburse these drug cocktails, that would mean a much longer lifespan.

1. Healthy Life Expectancy Trends, CBS, 2014
2. Nuo Sun, The Mitochondrial Basis of Aging, 2016
3. N. Barzilai et al., Metformin as a tool to target aging, Cell Metabolism, 2016
4. First in-human trials of senolytic drugs encouraging, Science Daily, 2019

Reversed aging in mice

A team of researchers has managed to reverse cell aging in old mice. This resulted in the bodies becoming younger in various ways. This discovery can have major consequences for understanding and curing diseases of the elderly.

Mitochondria as power plants
The first cells were unable to use oxygen. It was not until about 1 billion years ago that our ancestor cells started to cooperate with free-living bacteria, which were able to use oxygen, could multicellular life develop. The offspring of these free-living bacteria are mitochondria, which have since lost most of their DNA, but still play a key role in our cells. Mitochondria produce ATP, the energy supplier for all energy-using enzymes in the cell. Enzymes are large protein molecules, a kind of nanorobots, each of which performs a specific chemical conversion. Mitochondria release glucose or fats through a complicated process (the citric acid cycle) govern with oxygen and give the released energy as ATP (en NADPH / NADP +, with the pair NADH / NAD +, which performs a similar role to ATP and also delivers electrons). More about NAD +, the reduced version of NADH, later.

Photos C and D were taken at a later age of resp. mice A and B. Source: JD Boer et al, Premature aging in mice deficient in DNA repair and transcription, Science, 2002

Faulty mitochondria 
Mitochondria produce some enzymes themselves, but some enzymes, which are necessary for the conversion of sugars and fats into ATP, are produced by the cell nucleus. That is why mitochondria and the cell nucleus must be precisely coordinated. As we age, mitochondria do not function as well. The result can include Alzheimer's disease and diabetes. To find out how this came about, studied Ana Gomes from Harvard Medical School and her colleagues examined the levels of messenger RNA (mRNA) encoding respiratory enzymes in the skeletal muscles of six-month-old and 22-month-old mice (two-year-old mice are elderly).

mRNA is the intermediate step in translating DNA into an enzyme, and it disintegrates in a few days, so you know exactly which enzymes are being produced at the time of measurement. They discovered that the amounts of mRNA in the nucleus in old mice did not decrease, but the mRNA produced by mitochondria did. In other words, it is the mitochondria that falter with age, not the nucleus, which still faithfully produces enzymes.

Lack of SIRT1  
These changes also occurred in mice lacking the enzyme SIRT1. It has been known for some time that this enzyme occurs in an increased manner in food restriction and longer life. These mice, as well as old mice, also have higher levels of the nucleus-produced protein hypoxia inducible factor (HIF-1α). It seems that the communication between the cell nucleus and the mitochondria depends on a chain reaction, of which HIF-1α and SIRT1 are part. As long as the SIRT1 content in the cell remains high and the cell nucleus communicates well with the mitochondria, there is no aging.

Previous research has shown that NAD + (produced by mitochondria) keeps SIRT1 in shape. It is also known that for unknown reasons the production of NAD + in old cells decreases, although no one knows why. This stops the communication between the former bacteria and the cell nucleus.

Boost NAD production with nicotinamide mononucleotide: elixir of eternal youth discovered?
The research team wondered whether it was possible to restore communication between the cell nucleus and mitochondria. For example by increasing the SIRT1 content in the cells. To test this, the elderly mice were injected twice a day with nicotinamide mononucleotide (NMN) - a molecule known to boost NAD levels in cells (thus restoring SIRT1). At the end of the week, the elderly mice appear to be reborn. The muscle wasting and inflammation stops and the mice have even developed a different type of muscle, more like that of young mice at six months old. Gomes, as befits a good scientist, remains cautious. “We found that manipulating this chain reaction can improve the function of mitochondria and slow down certain aging diseases in old mice, providing us with a new method to reverse certain aging phenomena,” said Gomes. Would NMN, already recommended by some as dietary supplement for type II diabetes patients, become the food supplement of the future?

Source: 
Ana Gomes et al. Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging, Cell, DOI: 10.1016 / j.cell.2013.11.037

'Anti-aging research more effective than cancer research'

If science were to focus on research to slow down and reverse aging processes, that would yield more health benefits than cancer research. According to a report by top researchers from the University of Southern California (USC), Harvard University, Columbia University, the University of Illinois in Chicago and other institutions, among others.

Cancer Research: Extremely Slow Progress
Cancer (malignant neoplasms) is the leading cause of death in many Western countries, including the Netherlands. Hundreds of billions of euros have been invested in cancer research worldwide. The results are not really great. Mortality from some cancers has fallen spectacularly. For example, the previously fatal blood cancer leukemia in 90% of the cases is now incurable in only ten percent of the cases; spectacular progress. unfortunately, leukemia is the exception rather than the rule. Despite hundreds of thousands of man-years of research, the cancer death rate is still high, averaging 40%. More and more researchers within and especially outside the field are wondering whether cancer research is being tackled in the right way, and whether research resources could not be better deployed elsewhere.

Without old age, no age-related diseases. Is this the egg of Columbus? Some top researchers think so.

More and more hope to stop aging
Life expectancy has increased by an average of two years per decade in recent decades. Unfortunately, the number of years in which we stay healthy grew a lot less quickly; in some countries, such as the US, this is even decreasing. The result is an explosion of chronic diseases: the extra life expectancy consists mainly of 'sick' years, for example years in which patients are treated for cancer. In addition to the continuing bureaucracy in healthcare, this is an important cause of the explosion in healthcare costs. Cancer is a typical disease of old age. Cancer is rare in young people. If we could somehow reverse the aging process, we could also largely prevent cancer and other aging diseases (such as diabetes, heart complaints, etc.). Until the beginning of this century, this seemed an unattainable dream. The last few years are, however a few groundbreaking discoveries done in tests on mice, among other things. Certain treatments have been shown to extend the lifespan of mice by up to fifteen percent. Not only that, the mice also stayed healthy longer.

Better safe than sorry
The researchers started calculating with the available data and compared the health benefits of cancer research with those of research into the prevention of aging. The results are staggering. Preventing aging diseases by stopping aging appears to be many times more effective than continuing to pull the crippled horse of cancer research. In these ways, many years of pain and suffering can be replaced by healthy, radiant years. This is an enormous progress not only for the patients themselves. The informal carers can then also put their energy into making the world around them better, instead of having to fight a deadly battle against an unrelenting disease. In fact, the researchers estimate that a change in focus would net American society $ 7.1 trillion. That's about half of the total federal debt. If we assume comparable figures for the Netherlands and the rest of the European Union, this would solve the debt crisis.
However, the retirement age will have to be raised a few years immediately, for example to 70 or 75 in 2050.

Source
Dana P. Goldman et al., Substantial Health And Economic Returns From Delayed Aging May Warrant A New Focus For Medical Research, Health Affairs, 2013, DOI: 10.1377 / hlthaff.2013.0052

Jiroemon Kimura: the oldest man of all time?

Jiroemon Kimura in 2011.

If all goes well, Japanese Jiroemon Kimura will become the oldest documented man ever this Friday, December 28. Born on April 19, 1897, he is the only surviving male from before 1900. Currently, the age record for men is held by Christian Mortensen, a Danish immigrant to the United States, who died in 1998 at the age of 115 years and 8 months. Kimura is currently in hospital due to mild dehydration but appears to be on the mend.

Mr. Kimura is already the oldest living man since April 2011, and he is also the oldest living person in the world as of last week, following the death of two elderly women in the United States earlier this month. It had been almost six years since the oldest person in the world was a man (women live an average of three years longer than men). After that, no fewer than ten women carried the title of 'oldest person in the world': it is not a title that you can enjoy for a long time.

Jiroemon Kimura was born in a very different world from the one we know. The world population in 1897 was about 1.6 billion people and has since grown more than four times. Kimura was born shortly before the first Antarctic expeditions, and at the time of the discovery of the electron. People like Friedrich Nietzsche, Queen Victoria and Otto von Bismarck were still very much alive during Kimura's birth. His life also overlaps with that of our fellow countryman Geert Adriaans Boomgaard (1788-1899), the first verified (and undisputed) 110-year-old in the world. Kimura belongs to the last 29 people of the 19th century.

It is estimated that there are now about 500,000 centenarians in the world [1], 1,800 of which are in the Netherlands [2]. The remaining life expectancy of these people is very low, only about a year. From your 100th to your 110th birthday, you only have a 50% chance of making it to your next birthday, even if you have no serious health problems. It's like tossing a coin every year that determines whether another year will be added. So about one in 1,000 centenarians will turn 110. By your 115th birthday, the odds of living another year have already dropped to 30% (only 8 out of 27 managed to reach 116 [3]). The health of such old people is very fragile. Even if they appear to look fine, they can die within weeks of a cold or fall.

As the coin example suggests, the number of people of the highest ages is mainly determined by chance. For example, all known over-117s (four women) lived in the 1990s. One of these, Jeanne Calment from France, even became 122. Remarkably, no one has passed 116 since 1999, even though the number is 113- and 114- people over and over are increasing steadily.

Men are doing well this century. Until now, three men have been shown to have turned 115. They reached this milestone in 1997, 2006 and 2012 respectively; the latest is Jiroemon Kimura, who has a reasonable chance of becoming the first male 116-year-old in April. If he doesn't make it to 116, it could be a long time before someone else does; the second oldest man is almost 3 years younger.

The Netherlands will have to wait a while before we have a chance to win a 115-year-old again. We have had one: Hendrikje van Andel-Schipper in 2005. At the moment the oldest Dutch woman and man are Egbertje Leutscher-de Vries (110) and former minister Gerard Helders (107).

The number of Dutch centenarians in 2010. Source Statistics Netherlands [2]

The future

Record ages will only continue to rise (but not steadily) in the coming years. This is due to the fact that nutrition and health care have improved significantly over the past century (such as vaccination programs, antibiotics, operations), but also due to the increasing number of births per year around 1900. By 2025, there are expected to be around 1.25 million centenarians [ 1], and the number of people aged 110 and 115 will increase roughly proportionally (with some delay). Also important is that the number of people with reliable birth documentation is increasing. Until now, it has been very difficult for people born outside the Western world and Japan before 1900 to prove their date of birth. Because many unbelievable claims of extremely advanced age have traditionally been made, an age above 110 is only verified when three documents can be shown. Unfortunately, there are also many correct claims that cannot be proven.

Great progress in aging will not be made until we can heal the aging process ourselves. This process includes cancer (uninhibited cell division due to damage to DNA), the poor production of new cells, the maintenance of malfunctioning cells, and the accumulation of proteins in and around cells. In the Western world, about 90% of people die from the effects of aging. So there is a lot to be gained here.
Given the rapidly improving medical technology, it is possible that these problems this century can be remedied. Life expectancy may then increase by more than 1 year per year (the 'actuarial escape rate'), whereas this is currently more than 3 months per year in the Netherlands [4]. Then accidents and (self) murder remain as the main causes of death.

Sources
[1] United Nations 2009
[2] Central Bureau of Statistics 2010
[3] Gerontology Research Group 2012
[4] Central Bureau of Statistics 2012

Buckyballs double the lifespan of rats

The discovery of buckyballs, the 60-carbon molecular soccer balls, started the carbon revolution, which eventually yielded carbon nanotubes and graphene (with many more materials in the pipeline). Yet this “primal” exotic carbon compound also appears to hide many secrets. Including their unexpected and remarkable medicinal effects. Will this also work in humans?

Buckminsterfullerene, also known as C60, fullerene, buckyball or molecular football, has remarkable medicinal properties.

C60 scavenges dangerous incomplete molecules
Researchers at the University of Paris and colleagues administered the molecule buckminsterfullerene, also known as the "molecular football," buckyball, or C60, to rats dissolved in olive oil. C60 is non-polar, so it dissolves much better in oil than in water. They discovered that the molecule roughly doubled the rats' lifespan, without any chronic poisoning symptoms. According to the researchers, the results suggest that the effect of C60, an antioxidant (a substance that scavenges free radicals; free radicals are dangerous incomplete molecules that snatch atoms from, for example, proteins or DNA and thus cause serious damage), mainly caused by illuminating oxidative stress (that is a temporary accumulation of dangerous free oxygen radicals, such as OH. or O :). Oxidative stress is common in older people and other animals and is the cause of much damage to body cells.

No permanent symptoms of poisoning were found
The researchers also found that the dissolved C60 was absorbed by the gastrointestinal tract and disappeared from the rat's body in a few dozen hours. "These important achievements in medicine and toxicology open the door to many potential biomedical applications of C60, including cancer therapy, neurodegeneration diseases and aging," said a researcher.

“C60 can be administered orally and is now produced at many tons per year, eliminating the need to resort to water-soluble derivatives. These are difficult to purify and, unlike pure C60, are sometimes toxic. ”

The combination of C60 and olive oil almost doubles the lifespan (longer continuous line). Source: article.

 

Promising drug
Since the year 1993, numerous studies have shown that C60 and C60-derived substances show remarkably high potential in various fields of medicine and biology, especially in the cleavage of DNA, as an aid in imaging tissue fragments, against UV and ionizing radiation, antiviral effect, the aforementioned anti-oxidant effect, the effect against plaque formation, against allergic reactions and the prevention of the development of angina pectoris, stimulation of the immune system and anti-tumor effects, promoting the outgrowth of neurons , transporting genetic material and even the growth of hair, according to the voluminous enumeration in the article in the journal Biomaterials.

Too good to be true?
Some caution is certainly in order. Rats differ from humans in many ways and it is also questionable whether other unpleasant effects of C60 that we do not yet know will occur in organisms that live much longer than humans.

Yet. If this effect appears to occur not only in rats but also in humans and also works against other forms of damage than those experimented with (chloroform poisoning), then we could have hit the jackpot in the fight against aging and devastating nervous diseases. Good news, also because buckyballs are not patented by a pharmaceutical giant.

Source: 
Baati T, et al., The prolongation of the lifespan of rats by repeated oral administration of [60] fullerene, Biomaterials (2012), doi: 10.1016 / j.biomaterials.2012.03.036 (free version)

'Memory loss in the elderly can be reversed'

Good news for older forgetful folks. At least: for the time being only for older fruit flies. Scientists at the Scripps Research Institute have figured out a way to reverse age-related memory disorders in fruit flies by stimulating neurons. This allowed them to amplify medium-term memories: from half an hour to several hours. In humans this would be a longer period.

A neuron. Source: Scripps Research Institute.

The researchers use so-called optogenetic imaging, a technique in which genetic manipulation is used to examine which neuron is stimulated by which memory. In these transgenic flies, the substance G-CaMP is used as a calcium detector. This substance becomes fluorescent when it comes into contact with calcium. As soon as calcium enters a neuron, a sign that the neuron is becoming active, the neuron that is being stimulated (and thus records the memory) lights up in laser light. After half an hour to several hours, the fly was again exposed to the same stimulus, a certain smell, and indeed the neuron in question appeared to light up again.

Bringing memories back to life
The next step went on. The researchers placed cold or heat-activated ion channels in the fly neurons, which are known to deteriorate with age, and use cold, or heat, to activate them. In both cases, medium-term memory was found to be successfully restored. The study shows that once the relevant neurons have been identified in humans, we can develop drugs to target these neurons. This is how we can save the memories that have been damaged by aging, said Ron Davis, chair of the Neurosciences Department.

Although humans and fruit flies are only slightly related, the very biochemistry that enables memory processes throughout the animal kingdom seems remarkably uniform. This would mean that everything we learn about memory formation in flies is applicable to human memory and memory impairment in humans, Davis said.

But do we want to keep remembering everything? Sometimes it is nice not to know things anymore. For example, unpleasant experiences.

Source: 
Ayako Tonoki and Ronald L. Davis, Aging impairs intermediate-term behavioral memory by disrupting the dorsal paired medial neuron memory trace, PNAS, 2012; DOI: 10.1073 / pnas.1118126109

Pill against aging in sight

It was a discovery with a bitter aftertaste. Rapamycin prolongs life, but causes diabetes. Now that researchers have managed to separate these properties of this drug, a new life-extending drug is emerging without the harmful side effects.

Live longer, but with diabetes
Rapamycin (sirolimus) is usually given to prevent the patient's body from rejecting the donor organ after a transplant and as a therapy for cancer. Previous studies showed that rapamycin extends animal life (in mice) by around fourteen percent, but at the same time increases glucose intolerance - a side effect also reported in humans.

Brazilian plaque commemorating the discovery of the rapamycin-producing bacteria, which has already saved the lives of many transplant patients. Incidentally, the bacteria produces more useful substances. Source: Wikimedia Commons

Action on two different proteins
David Sabatini of the Whitehead Institute for Miomedical Research in Cambridge, Massachusetts, and his colleagues gave the drug to genetically engineered mice with the genes for rapamycin's target proteins turned off. In doing so, they discovered that rapamycin responded to two important nutrient-responsive proteins, MTORC1 and MTORC2 (mammalian target Of rapamycin complex 1 and 2).

Rapamycin has been discovered in the soil bacteria Streptomyces hygroscopicus, a bacterium that occurs on Easter Island (Rapa Nui). The substance suppresses the immune system.

After the study, it became known that the action on the gene for MTORC1 prolongs life, while the action on the gene for MTORC2 causes diabetes.

Only life extension
Sabatini's team is now working on a form of rapamycin that only acts on MTORC1. If that succeeds, and the researchers can prevent their new variant from causing unpleasant effects elsewhere in the cell, a drug would be created that could effectively extend the lifespan by a number of years. If the effect would be as strong as in mice, it would be an average of ten years in humans. This comes at a price: even after elimination of glucose intolerance, suppression of the immune system means a reduced resistance, including against certain cancers. So don't cheer too soon.

The second step to a thousands of years old human dream: immortality, is getting closer. (The first step, discovering healthy living habits, is already commonplace). Incidentally, life extension in itself is not the most interesting goal. We have been living ten years longer than before the Second World War, but unfortunately the period without chronic diseases is just as long. The real challenge is to extend the time that people live without chronic disease, so that the quality of life improves significantly and it also becomes worthwhile to extend the time that we stay alive.

Sources:
David M. Sabatini et al., Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity, Science (2012), DOI: 10.1126 / science.1215429 (paywall)
Pill against aging a step closer, Kennislink (2012)

Many age-related diseases result from cloudy lens of the eye

As it turns out, many puzzling old-age complaints have a simple cause. The lenses of the eyes of old people no longer transmit blue light, which disrupts their daily rhythm and affects their health.

Declaration overlooked for decades
What do memory loss, slower reaction time, depression and insomnia have to do with each other? All are aging symptoms that have remained unexplained until now. Medical researchers tried everything from high cholesterol and obesity to cardiovascular disease and too little exercise. However, an ever-growing body of evidence suggests that there is likely an entirely different cause: aging of the eyes.

Light therapy can cause health problems such as insomnia in older people. take away depression and daytime sleepiness. Source: Wikipedia

Yellowing lens blocks blue light
As people age, the lens turns yellow and the pupil narrows. This disrupts the body's daily rhythm, which in turn leads to many physical problems. As the eyes get older, less and less sunlight penetrates the lens, so that the very important cells in the retina no longer have the stimulus to regulate the body's daily rhythm, our internal clock. "We believe the effect is enormous and is only now being truly recognized as a problem," said Dr. Patricia Turner, an ophthalmologist in Leawood, Kansas, who and her husband Dr. Martin Mainster, a professor of ophthalmology in the university's faculty of medicine. Kansas has already published extensively on the health effects of aging eyes.

Consequences of disruption of the day-night rhythm: insomnia, more heart complaints and a greater risk of cancer
Day-night (circadial) rhythms are the cyclical hormonal and physiological processes that wake up and activate the body in the morning and put it into repair mode at night. This biological clock depends on light. People with irregular day / night rhythms, such as those who work shifts, are at higher risk for a number of conditions such as insomnia, heart complaints and cancer.

Special photoreceptive cells in the retina collect sunlight and send a signal to the suprachiasmatic nucleus (SCN), which regulates our biological clock. The SCN 'serves' the body with a dose of melatonin in the evening and cortisol in the morning. Melatonin puts the body in a rest and repair position; people who secrete little melatonin (a sign of a faltering SCN) are more likely to have diabetes, heart disease and cancer. It was only discovered in 2002 that a special type of cell existed. Until then, scientists assumed that the well-known rods and cones provide the stimulus. After this discovery, it was also known that these cells respond to blue light and communicate directly with the brain. Just the type of blue light that energy-efficient bulbs emit.
Unfortunately, it is precisely blue light that is filtered by the yellowing lenses. It is estimated that a 45-year-old only receives 50% of the required amount of blue light for maximum stimulation of the SCN. This is 37 percent for 55-year-olds and only 17 percent for 75-year-olds. according to a publication by the couple. European research shows that daylight does have an effect on lowering melatonin levels in young women, but not in middle-aged women. These seem to require a much higher dose of blue light to compensate for the yellowing. For this reason, in younger people, exposure to blue light also results in higher alertness, less sleepiness and an improved mood. The reason our mood is usually better on a sunny day.

Replacing a cloudy eye lens cures insomnia and daytime sleepiness
Swedish researchers also found that patients who underwent cataract surgery (surgery in which the clouded lens is replaced with a clear artificial lens) had much less daytime sleepiness and nighttime insomnia. Another study found improved reaction time after surgery. Turner believes that cataract surgery will eventually be shown to result in a higher level of melatonin, which means that these people also suffer less from cancer and heart complaints. They also wonder whether it is smart to build in a filter in the lens against blue light, as is happening now. This would prevent macular degeneration, but the scientific evidence for this is questionable. The need for blue light, on the other hand, is becoming increasingly clear.

More bright indoor lights with a lot of blue
The elderly, who spend a lot of time indoors, are especially at risk. Artificial light is about 1000 to 10,000 times less dim than sunlight. To make matters worse, artificial light is in the wrong part of the spectrum. No wonder, then, that the already graying Dr. Mainster and Dr. Turner have installed extra bright lighting in their own office to compensate for the aging of their eyes.

Source:
New York Times

'Elixir of life' extends life by 15%

Finally, a first serious candidate for an elixir of life: an enzyme found in humans is capable of extending the life of mice. There are many differences between mice and humans, but still, given the universality of sirtuin, this is a very promising candidate.

False hope…
Hopeful reports about sirtuin-2, one of the seven variants of the enzyme sirtuin found in mammals. The enzyme appeared to be able to dramatically increase the lifespan of pinworms, yeast cells and fruit flies. Unfortunately, this hope was dashed in the 2010 experiments with worms and fruit flies. The experiment in which this was “demonstrated” turned out to have been set up in the wrong way. Yeast is a single-celled organism that is genetically very different from a human, making these results less relevant.

Domestic mice live about 1.5 to 2.5 years. SIRT6 extends their life with 15%. Image source: Wikipedia

Or not?
Mammals like humans, however, have seven types of sirtuin. Haim Cohen and Yariv Kanfi of Bar-Ilan University in Ramat Gan, Israel, decided to experiment with another sirtuin, sirtuin-6 (SIRT6), this time on (much more closely related) mice.

They compared mice that produced extra SIRT6 as a result of changes in their DNA with normal mice. In order to rule out systematic errors due to the chosen techniques of genetic engineering, the mice were genetically 'processed' in two different ways, creating two test groups.

Live fifteen percent longer
Male mice from both groups of genetically engineered mice lived 15% longer than untreated or female mice. In humans, this would amount to ten to twelve extra years of life. Older genetically modified male mice were found to break down sugar faster than normal mice and females. This suggests that SIRT6 extends life by protecting against metabolic diseases such as diabetes.

It is not clear why SIRT6 did not extend life in the females, but this may be due to differences in genes that regulate aging in males and females.

Source:
H. Cohen et al., The sirtuin SIRT6 regulates lifespan in male mice, Nature, 2012

Special food supplement slows down brain aging

Professor David Rollo and a group of researchers from the Canadian McMaster University have found a 'golden bullet' with which they can stop the aging of the brain. Good news, at least if you're a transgenic mouse.

Also relevant for people
Yet this could also be very interesting for people. Partly because similar ingredients prevent the brains of Alzheimer's patients from shrinking in a study published at the same time.

Dietary supplement leaves older mice brains young
In the latest scientific paper, the group describes a new dietary supplement that fully preserves the ability to learn new things in older mice. Not only important, but even remarkable, says Rollo.

Composition of the dietary supplement
The food supplement contains around thirty ingredients. Unfortunately, we have not yet managed to get to the primary source (we have to deal with press releases and this summary [4]), but the following ingredients were mentioned in the sources I consulted: 

provitamin A (beta-carotene)
vitamin B1 (thiamine)
vitamin C (ascorbic acid)
vitamin D (cholecalciferol)
vitamin E (tocopherol)
Ginseng (Panax ginseng extract)
Green tea (unfermented Camellia sinensis, extract)
Cod liver oil
a number of unspecified acids and minerals.

Update: good news, the full list can be found here.

This dietary supplement is specially designed to counteract five aging mechanisms.

Supplement tested on elderly mice
The mixture was tested by Rollo's group on 20-31 months old aged mice. One group received the supplement, a control group did not. The control group was hardly able to learn new things, the group with the supplement scored just as well as young mice.

Eating lots of vegetables is an absolute must to keep your brains up to scratch, it turns out.

Brain mass 10% greater; more active mitochondria
The behavioral tests focused on an area of the brain affected by Alzheimer's disease. Analysis of the animals' brains showed that their brain mass was ten percent larger than that of the control group. The mitochondria, the 'energy centers' of cells, also turned out to be much more active in the control group.

Rollo remains cautious, because this is a first experiment, but believes it is quite possible that the supplement also has similar effects in humans. Of course, humans live much longer than mice, which means that these kinds of tests take a lot more time.

Scavenging free radicals and keeping mitochondria alive
The new nutritional supplement fulfills two functions that are very important according to anti-aging research: the scavenging of free radicals (incomplete molecules that are chemically very aggressive and thus cause much damage to DNA and enzymes, among others) and the maintenance of the energy function of mitochondria. The combination of ingredients proves to be much more effective than individual vitamins, pills and anti-aging products in protecting the brain from aging.

Solution for Alzheimer's and Parkinson's?
Although the human trials have yet to begin, Rollo is hopeful that the dietary supplement will one day slow down or even stop brain diseases such as Alzheimer's, Parkinson's and the like. This would then provide an affordable, natural form of medication for the elderly. (1)

Supported by research on humans
Another article, this time from our American colleagues at Science Daily (2), who fortunately have the decency to always cite scientific sources, reports a similar study, but in humans.
Eighty-year-old elderly people who consumed a diet rich in omega-3 fatty acids and vitamins B complex, C, D, and E scored significantly better on thinking tests than people who did not eat such a diet.

Omega-3 fatty acids and vitamins make you smarter; unhealthy snacks dumber
Omega-3 fatty acids and vitamin D are especially common in oily sea fish. The various B vitamins (B1, B2, B6, folic acid, B12) and the anti-oxidants C and E (C acts as an antioxidant in a water-rich environment, E as an antioxidant in greasy environments such as cell membranes) are found in vegetables, fruits and (vitamin E) in nuts.

Trans fats turned out to have the opposite effect. In people with a high percentage of trans fats in their diet (from processed foods and margarine), brain function was found to have deteriorated.

Blood tests show an accurate link
What is special about this study is that blood tests were used to check exactly how high the blood levels of these substances were. People don't always know exactly how much of which foods they ate. Blood tests provide a more reliable picture. Indeed, there appeared to be a large statistical correlation between the measured values and the effects on the brain: 17% of the total variation. Known factors such as blood pressure, education and age were also responsible for 46% of the variation. The biomarkers explained 37% of the variation in brain size. (3)

Sources
1. Silver bullet supplement could slow brain aging - McMaster University News (2012)
2. Alzheimer's: diet patterns may keep brain from shrinking - Science Daily (2012)
3. GL Bowman et al., Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging, Neurology (2011)
4. Vadim Aksenov et al., A complex dietary supplement augments spatial learning, brain mass, and mitochondrial electron transport chain activity in aging mice, AGE (2011) (paywall)

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