The researchers are working on the relationship between body cell condition and aging. Their experiments have shown that the presence of stem cells or progenitor (undifferentiated) cells can have a beneficial effect on cells afflicted with either progeria or simple old age. Merely injecting the stem cells had an impact on cells in the brain and muscles. In experiments conducted with cells in a culture dish, the proximity of stem cells – close but not touching – had a beneficial effect on unhealthy cells.

Rather obviously this research begs a question: What do the stem cells do to the aging cells? This type of research is pretty much a ‘black box’ experiment. The cells are injected and the results observed, but the chemistry or molecular-level pathways are not known. Which is why further research is required. However, it should be noted that a lot of medicine is used in which the results are accepted without knowing the underlying mechanism. These days, however, as equipment and procedures for work at the molecular level improve, it should be possible to take this kind of top-level research and successfully look for low-level linkages to the aging process.

What appears to happen is that the prefrontal cortex accumulates too much of the signaling molecule known as cAMP. It opens too many ion channels (the primary means of generating neuronal firing), which weakens the neurons. The researchers went to the medical chemistry shelf to look for agents that either inhibit or block cAMP sensitive ion channels and came up with guanfacine, a relatively common drug (Tenex is its proprietary name) used to treat attention deficit disorder (ADHD), anxiety attacks and sometimes high blood pressure. After applying this drug to older animals, they found that significant neuronal firing rate capacity was restored; again implying better short-term memory.

What’s significant here is not just that this is another shot at extending the length and quality of life, but that it has a reasonable scientific background AND it is moving into clinical trials (stage one). That is the significant part. If guanfacine proves to have beneficial effect on the memory of the elderly and doesn’t show any dangerous side effects or long-term problems – add it to the growing armamentarium against old age. It’s on such advances that the claim of human beings living to (at least) 150 years is made.

There is a hint of spaghetti-hitting-wall technique in this. (You know, the old “throw spaghetti against the wall and see what sticks” method of determining experimental evidence.) Or perhaps a taste of the magic elixir from the fountain of youth. But then, the search for longer, better life is probably as old as our awareness of aging and death. Sometimes solutions are found long before we know precisely why they work.

For most people that would include cancer (in all its many forms) and heart disease (also in many forms). After these two, selection becomes a little more difficult: AIDS, malaria, cholera? Diabetes, influenza, lung diseases (many forms)? Dementia…dementia also comes in many forms, the most well-known being Alzheimer’s disease. Dementia is global, severe in its effects, and very difficult to treat, much less cure. But how prevalent is it?

A new study, intended to be the most comprehensive yet: The World Alzheimer Report 2010, was released September 21, 2010 by Alzheimer’s Disease International and authored by Anders Wimo (Karolinska Institutet, Stockholm, Sweden) and Martin Prince (Institute of Psychiatry, Kings College, London, UK). The study focuses on the economic impact of Alzheimer’s and related diseases. (Technically, dementia is the broad category, with Alzheimer’s one of the many types of dementia).

While the figures are not new to health professionals, the standout statistics from the report are something of a ‘bang’ in terms of mass media (and intended to be so):

- The cost of dementia will exceed 1% of global GDP in 2010 – US$ 604 billion.
- The number of people with dementia will double by 2030, triple by 2050.
- The cost of treating dementia is rising, partly because of greater awareness and partly because of more sophisticated treatments

We – including many people in the under-developed parts of the world – are living longer. When humans live beyond seventy years, the chances increase for brain deterioration in some form of dementia. Statistically as populations of elderly enlarge, so does the incidence of dementia.

There is accumulating evidence that ‘modern lifestyle’ (bad diet, lack of exercise, stress, lack of sleep, abusive pharmacology) contributes to the occurrence of dementia.

In many parts of the world it is a rare extended family that does not have someone afflicted by dementia.

The pace of research on dementia has been increasing in the last decade, but the disease is elusive. For one thing, it’s beginning to look like even the mild symptoms of ‘aging forgetfulness’ are caused by the earliest appearance of dementia – which makes it much more widespread than first thought. While some apparent causes of dementia have been isolated – plaques in brain cells, certain genes (I’m leaving out lots of details) – the linkages are uncertain, meaning they haven’t been worked out at the chemical/molecular level.

Laboratories from academia to Big Pharma are busy looking for ways to treat the various forms of dementia, so far with limited success. However it is rare that a week goes by without some announcement relating to dementia. There may be a breakthrough at some point, but more likely various approaches and treatments will develop over time. Researchers may get lucky with this or that drug, but without an accurate understanding of what dementia is (at the molecular level within the neuron) and what factors are involved in its development, a true ‘cure’ is unlikely.

Dementia is an immense challenge, one not unique to the 21st century but perhaps a hallmark disease of our times. It is both a symptom and a result of our longer lives – a tradeoff of a sort – that affects millions of people and their families with usually devastating results. It is a major disease.

A team of Princeton scientists, headed by Coleen Murphy, assistant professor of molecular biology, wondered if these two approaches to increasing lifespan had any impact on cognitive ability. (For ‘cognitive’ read ‘mental functions’ including perception, recognition, memory, problem solving, and ‘thinking,’ however that is defined.) Their research, published May 18 in the Public Library of Science, Biology shows that as is so often the case, there are trade-offs.

The scientists chose as their laboratory specimen the old friend of the biologist, C. elegans, the flatworm. The worm has a simple nervous system, which makes it easier to study. It also has a short lifespan, about two to three weeks, which makes cause and effect in the aging process much easier to observe than in say, humans, who take decades to show signs of aging. Of course, what is observed in flatworms does not directly or perfectly translate into identical observations in humans – but there are important and fundamental similarities based on activity at the molecular level. That is what interests the scientists.

Another reason for choosing C. elegans is that mutant varieties have been developed with long life spans (exceeding three weeks). Comparing these worms with their normal brethren could provide insight concerning the effects of diet and insulin. However, there was an interesting question: How do you measure the cognitive ability of flatworms? You don’t exactly hand them a questionnaire, however, you can make them take a test. In fact, a test Pavlov (and his dogs) would have recognized.

The worms were trained to associate food (nice juicy bacteria) with the smell of a chemical called butanone. To humans butanone smells like a sickly sweet combination of butterscotch and acetone. Who knows what it smells like to a flatworm, but they generally avoid it – not, however, when there’s food to be had. After a specific length of training, the worms were tested over a period of days for their reaction to the smell of butanone: if they moved toward the smell, they remembered the association with food. If they didn’t move toward it, the association was forgotten.

It turned out that normal worms have pretty good memories. After seven 15 minute training sessions, young worms could be motivated by smell=food for at least 16 hours. (Translated into human scale, that would be the equivalent of remembering something for 3 to 6 years.) This ‘long term memory’ in the worm would fade after about 24 hours and totally disappear after 40 hours (again, this is roughly 8-15 years in human terms). Not bad, however, the tests also showed that after four days of adulthood, normal worms lose their ability to form any long term memories.

The result with the mutant (long lived) worms was more revealing. One of them has a defective gene for the use of insulin; the other a genetic defect that limits the amount of food it can ingest. The mutant worm with calorie restrictions had normal short-term memory but severely impaired long-term memory – less than 24 hours compared to 40 for the normal worms. However, they could continue to form long-term memories well beyond the normal 4 day limit. The insulin deficient worms had yet a different pattern: their short-term memories lasted much longer, about six hours (3 times normal), but long term memory lasted a normal 40 hours. They could form short memories for a longer than normal time, but long-term memories could not form after the normal 4 days.

These results confirm that the insulin and dietary conditions which affect longevity also affect cognitive ability – sometimes positively, sometimes not.

The researchers were able to find a commonality for the effect among the worms, which was a protein identified as CREB. This type of protein binds to DNA to regulate the expression of genes and has been associated with long-term memory in many other animals. In the worms, it also has a crucial role in the formation of long-term memories, but no role in short-term memory. For example, in young flatworms with insulin deficiency, there was a high level of CREB, which correlates to their stronger long-term memories. This and other correlations point to CREB as a focal point for further studies at the molecular level. The research team will use DNA microarray techniques to look for other proteins that may be involved in the cognitive ability of aging. As Dr. Murphy explains:

“I’m optimistic because we know these longevity mechanisms in C. elegans are conserved in higher organisms, and there are reasons to believe that they could have similar effects on lifespan and cognitive function in humans,” she said. “But these results also suggest that not every way of extending lifespan is good for cognitive function, which has huge implications for the development of therapies to maintain memory.

[Source: Princeton University]

Telomeres are ‘tag ends’ of our DNA chromosomes. In the process of reproducing cells, the telomere signals where to stop transcribing genes. However, during the process of mitosis, when the DNA duplicates and a new cell is created, sometimes the telomere is cut (snipped) before the end. It becomes shorter. Eventually there may be no telomere remaining, and the cell will fail to replicate. This has been shown to relate to the aging process (SciTechStory, November 9, 2009: Study confirms telomere’s role in living longer).

Normally DNA attempts to keep the chromosomal telomeres at the proper length. In fact, it has at least one gene associated with the task: telomerase RNA component or TERC. The research shows that some people have variations, either in TERC or genes associated with it that prevent TERC from working properly. These people age early, or fall prey to diseases of old age earlier.

Professor Tim Spector from King’s College London and director of the TwinsUK study, who co-led this project, added:

“The variants identified lies near a gene called TERC which is already known to play an important role in maintaining telomere length. What our study suggests is that some people are genetically programmed to age at a faster rate. The effect was quite considerable in those with the variant, equivalent to between 3-4 years of ‘biological aging” as measured by telomere length loss. Alternatively genetically susceptible people may age even faster when exposed to proven ‘bad’ environments for telomeres like smoking, obesity or lack of exercise – and end up several years biologically older or succumbing to more age-related diseases. ”

[Source: EurekAlert]

Identification of the variant genes is, of course, just a start. Analyzing the relationship between ‘normal’ and ‘variant’ genes and how they affect the reproduction of telomeres is a next step. As with much of the work on gerontology – this avenue of approach is many years away from producing something to counteract the effects of aging.

Almost a third of the “impact areas” listed here at SciTechStory contribute to the coming reality of an Extended Lifespan (also an impact area): DNA Decoding, Cell Biology, Brain Enhancement, Medical Robotics, Major Disease Cures, Nano-medicine, Bio-implantation, Neuro-intelligence, Scientific Instruments, Sensor Technology, Stem Cells, and Synthetic Organs. Collectively these impact areas represent the research work – and important advances – in a fleet of disciplines: Neuroscience, genetics, molecular biology, nanotechnology, robotics, gerontology, pharmacology…to name but a few. It’s not like expanding the span of human life is the be-all-end-all for most of this research, but for most it’s a direct result. If major diseases can be cured, people will live longer. If cell biology discovers how to reverse the deterioration of aging, people will live longer. If body parts can be repaired or replaced through bio-implantation, synthetic organs, or stem cells, people will live longer. And so forth…

A recent article in the English publication, The Guardian, highlighted the issue: Great expectations: today’s babies are likely to live to 100, doctors predict.

Most babies born in the past few years in the UK will live to be 100 if current trends continue, experts say.

And people could be living not only longer, but better, according to doctors writing in the Lancet medical journal, who say that most evidence shows the under-85s are tending to remain more capable and mobile than before. They have more chronic illnesses, such as cancers and heart conditions, but people survive them because they are diagnosed earlier and get better treatment.

Professor Kaare Christensen and colleagues at the ageing research centre at the University of Southern Denmark calculate that at least half the babies born in the UK in the year 2000 will reach their 100th birthday. Life expectancy is increasing so fast that half the babies born in 2007 will live to be at least 103, while half the Japanese babies born in the same year will reach the age of 107.

The ‘we’re going to live longer’ scientific literature is becoming common. Perhaps you have heard or read about it yourself. Do you believe it? [Personal anecdote: My father was lamenting to my aunt about the poor state of the world. This was in 2001. My aunt replied, “Yes, but we’re living longer.” She died at 93, despite life-long epilepsy and eventually Alzheimer’s. My father lived to 99.] The confirming statistics are everywhere: The number of centenarians is increasing by about 7% a year. The average life-span in Medieval Britain was 20-30 years. By the early 20th Century it was 30-40 years. Now it is approximately 75 years.

The question about when this will happen – when will most people live to 100? – is answered by “starting now, in developed countries.” Starting probably within a few decades for much of the rest of the world. Keep in mind that the world average is already at 65 years of life.

All this means that we’d better not forget demographics when it comes to looking at the future. For example, how should we plan for social security (of whatever kind), when people routinely start living 90-100 years? What happens to the nature of work, and employment, when the difference between the end of work (now around 65) and death is no longer ten or twenty years, but thirty and forty years? How do our health care systems adjust to a radically aging population?

These questions barely scratch the surface.

Meanwhile the research goes on, not just apace but at an advancing pace. People living now will benefit from the discoveries yet to come, but it’s our children who will see the most change and have to deal with the most consequences.

Berkeley — A study led by researchers at the University of California, Berkeley, has identified critical biochemical pathways linked to the aging of human muscle. By manipulating these pathways, the researchers were able to turn back the clock on old human muscle, restoring its ability to repair and rebuild itself. The findings will be reported in the Sept. 30 issue of the journal EMBO Molecular Medicine, a peer-reviewed, scientific publication of the European Molecular Biology Organization.

The key point from this post in FuturePundit is that, yes we can probably induce more repair to muscle cells in older people, but there is almost always a trade off. Maybe we should call it the ‘trade-off principle’ of research, and apply it systematically.

If the body is turning down MAPK and suppressing stem cells as we age there’s probably a constructive reason for this. The most obvious possibility: the repair stem cells are turned down because as they age they become higher risks for turning cancerous. If that is the case (and I think it likely) then efforts to turn up stem cells to do more repair will put us at greater risk of cancer. Therefore we really need effective ways to kill pre-cancerous and cancerous cells as essential capabilities in order to do rejuvenation therapies.