Spock really cuts to the core of success with his Star Trek catch phrase. A person has truly succeeded if he or she has led a long meaningful life, perhaps with many children or a great legacy. Recent information may be cracking open the door to the former part of this common expression. The new understanding of the signaling pathways underlying aging may lead to a longer lifespans, but whether or not they will be prosperous is still to be seen.
An important factor in aging is the insulin pathway. Some new studies have shown that by blocking this pathway in a number of ways such as, genetic blocking, medication or simple caloric restriction, have increased the lifespan in a number of animal models. However, things don’t seem to be so easy in the far more complex signalling of humans, but big steps do seem to be being made. We seem to still be a long way off from increasing lifespan by exploiting this new-found information, but now is as good a time as any to discuss whether longer life would lead to more prosperity.
On the plus side, some diseases such a Alzheimer’s Disease are directly related to aging, and slowing the aging process might be a key to stopping or slowing the influence of this hated disease. The same insulin pathway mentioned earlier may play a part in the disassembling of structures within brain cells, which may be a major cause of AD. So slowing the aging process through manipulation of this pathway may lead to longer cognition as well as longer life. Perhaps slowing the aging process would add another few years of activity to the average person. This would lead to increased productivity and therefore prosperity across the board.
Unfortunately, it isn’t mentioned if this pathway would extend the utility of the body. I would hope that it does, but it seems a possibility that the blocking the insulin pathway may lead to a longer life, but maybe one much extra vigor or energy. To me, just living an extra ten years in bed does not seem too great a prize. A widely available increase in lifespan would also put extra strain on society. We can barely pay for the aging American population when the average lifespan is about 80, imagine another ten or even five years tagged on the end. With this in mind, prosperity doesn’t seem like a definite offshoot of longevity.
In closing, I would suggest that research continue, if for nothing else than the knowledge. Plus, we’ll never know whether aging research will lead to the more prosperous first scenario or the second, less desirable scenario without a better handle on the complex issue of aging.
Tough Questions with Science: Immortality?
Earlier this week a person of great interest passed away, leaving us with an inquisitive quote on death:
“No one wants to die. Even people who want to go to heaven don’t want to die to get there. And yet death is the destination we all share. No one has ever escaped it. And that is as it should be, because death is very likely the single best invention of Life. It is Life’s change agent. It clears out the old to make way for the new. Right now the new is you, but someday not too long from now, you will gradually become the old and be cleared away. Sorry to be so dramatic, but it is quite true.” –Steve Jobs
As scientists dive further into the workings of our body more becomes known. In today’s world some of the biggest questions revolve around prevention and reversal of diseases. As researchers work towards a full understanding of the brain, they sometimes stumble upon results leading to increased longevity. An example would be this week’s article in neurochemistry stating that the IGF1-R neuroreceptor in the brain might be a common causality of Alzheimer’s disease and aging of the brain. IGF1-R can lead a chain reaction that produces Aβ plaques which have long been believed to cause Alzheimer’s. On the other hand when IGF1-R is activated, it also creates a chain reaction that produces FOXO proteins which can lead to aging. This suggests that with some tweaking of IGF1-R pathways the length of a person’s life may be increased. Of caurse as I have mentioned in my previous blog post the body is extremely complicated and “tweaking” isn’t as easy as it sounds. Plus there are always bound to be side effects.
Yet even if we do begin to understand the chemistry of aging, is that something we want to modify? Just because a person can live longer doesn’t mean we live better. As chemistry begins to answer more difficult questions, it seems that ethical debates are likely to follow. I don’t know what the next 50 years holds, but I promise it will be interesting.
(1) Apfeld, J.; O’Connor, G.; McDonagh, T.; DiStefano, P. S.; Curtis, R. The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev 2004, 18, 3004-3009.
(2) Puglielli, L. Aging of the brain, neurotrophin signaling, and Alzheimer’s disease: Is IGF1-R the common culprit?. Neurobiol. Aging 2008, 29, 795-811.
Dear Dad, Remember me? Links between Alzheimer's and food
Alright Dad, I’m just trying to look out for you when I say this, put down the gallon of ice cream that I know is in your lap. Yeah I know you work real hard and have never been at risk for being over weight, but this is about your memory. I learned in class this week that there may be a link between calories you eat and Alzheimer’s Disease.
There have been a few studies that show how restricting your calories can partially block a pathway in the brain called Insulin Growth Factor 1 (IGF1). When we eat a lot of food and take in more calories than we can burn, this activates insulin in the body so that we can store some of these calories to use later. But insulin not only stores these calories for later use, it can also activate this pathway that causes aging and Alzheimer’s. Alright, so what if we could just block some of this insulin then we can prevent Alzheimer’s completely?
That would seem like common sense but in actuality, it never works like that. Our brains and bodies have such delicate balances of everything. We need some amount of insulin to store our calories for energy, but we can’t have too much or it may cause cancer? Some scientists tried to study more about blocking insulin in the brain through studying mice. They completely shut off insulin in the brain, and found that it didn’t increase the lifespan of the mice at all, it actually decreased the life span.
So what’s the moral of the story? There may be a link in between food and the brain so eat healthy and in moderation. It isn’t just about cholesterol, heart disease and obesity anymore. It’s about your memory.
Alzheimer’s Disease: Where We Stand on Treatment
First off, I’m sure you have all at least heard of Alzheimer’s Disease (AD), and how it causes its victims to lose their memory. I bet, however, that most of you don’t know what the cause of AD is. You aren’t alone though, researchers have been trying to determine what the main cause of AD is for years. They have nailed down several possible etiologies. One theory is that the symptoms of AD start through the aggregation of tau proteins. Tau proteins are in charge of keeping the microtubules of the axon in the neurons in good shape. They regulate the microtubules and keep the neuron’s axon healthy. However, in AD, those tau proteins get over phosphorylated, and this causes them to diffuse away from the microtubules and form clumps making them unable to regulate the microtubule. When the tau proteins aren’t present next to the microtubules, they then fall apart, causing degeneration in the neuron. This video, courtesy of youtube, is a great animated cartoon showing this very process.
Well, why is this important? Neurons fire their signals through the axon, and without the tau proteins, those signals can’t be sent. This is why people who suffer from AD have symptoms such as memory loss and loss of motor control.
So, it should be no surprise that research is going into a medication that stops tau protein clumps from forming, and there is a scientific paper about it.
This paper stated that a new drug was being synthesized, and that patients who suffered from AD were took it showed improvement in their symptoms as opposed to a placebo group. This is great, but my question is this, is this really where research should be focusing? Sure, it alleviates symptoms for AD, but it cannot rebuild what has already been lost. I think research should be focusing on early detection, and looking at early onset AD to figure out what is actually going wrong in AD patients. What are your thoughts?
Fountain of Youth Found in Neuroscience
The brain is filled with an intricate weaving of signaling pathways and transmissions. A negative affect that arises from this complicated web is the accumulation of deposits of amyloid plaques and neurofibrillary tangles, which cause Alzheimer’s disease. Understanding how theses pathways affect each other can help us prevent or cure AD.
Insulin signaling has an important role in the brain and is connected to the amyloid beta plaques and tau tangles. Insulin resistance is an issue that can worsen AD. When someone is insulin resistant, cells do respond properly to insulin, thus insulin cannot get into the brain as well. This throws off the concentration of insulin in the brain, which is very important for memory and cognitive functioning.
Curing AD could only just be the start of medical advancements coming from further understanding of neuropathways. Protecting the brain from age-related neuronal loss could be a possible use of this information to expand the lifespan of humans. Doing this would bring up many moral and social issues that would become involved. Playing god could be one objection along with increasing heath care costs for the elderly. A lot more work and research needs to be done before this could become a reality. If longevity of a lifespan was desired, manipulating these complex pathways could solve the mental aspect.
Discovering an Elixir to Immortality
Imagine a world where age has no effect on what we do with our lives. People could live forever, choose multiple careers, and pretty much do whatever their heart desires. In today’s reality, this is physically impossible, but researchers have found a link between variants of the gene FOXO3A (Forkhead box O3) and people who live past 100.
As medicine continues to advance life expectancy, more and more people are becoming interested in longevity. Although aging is not an exact science, scientists do know the genetics and external factors that determine one’s life expectancy. Everyone, not only centenarians, has a FOXO3A gene. It has been found that FOXO3A variants are primarily common in centenarians. However, it is the variation of a unique section of the gene that is an area of interest. More specifically, single nucleotide polymorphisms are where the variations reside. Within these variations lies the key to longevity, and scientists want to discover, through DNA tests and genome sequencing, the specific single nucleotide polymorphism linked to aging.
Here is where a question of ethics develops. If scientists are able to locate the specific section of the gene, is it morally right for people to know how long they will live? Do we continue with research in the attempt to alter our genes in the hope of living longer? These impending questions are growing closer and closer as scientists experiment with genetic manipulation on mice. The results gained from these experiments may lead to extending life or even prolonging our youth. It is society’s responsibility to weigh the positive and negative effects of a possible life-extending drug.
Confused About Treatments? Everyone Is.
With as much research as there is about Alzheimer’s Disease, there are surprisingly few conclusions as to its possible causes. Through the article of the week and classroom investigations into the different areas involving Alzheimer’s, much was learned about the possible mechanisms of Alzheimer’s but few conclusive answers were found. For example, Aβ protein segments that accumulates to form amyloid plaques have long believed to be an underlying cause of Alzheimer’s, as has tau aggregation and the forming of neurofibrilary tangles. Given the ambiguity of the causes of Alzheimer’s I was interested in finding out what treatment plans are being investigated. The alzheimer’s association has a section on their website that describes both completed and on-going studies that test different drugs in the hope of finding a treatment for Alzheimer’s: http://www.alz.org/research/science/alzheimers_treatment_horizon.asp?type=more_information . The wide array of mechanisms that these drugs work through are yet another example of how scattered Alzheimer’s research is. ACC-001 and AN-1792 are ‘vaccine’ type drugs that target the Aβ, and bapineuzamab is another drug that targets Aβ, but while still in process, researchers are still not sure if reducing Aβ levels will be an effective treatment for Alzheimer’s. Yet other drugs, such as methylene blue work to prevent tau protein aggregation. The Alzheimer’s Association also reports that a future successful treatment will include a ‘cocktail’ of different medications, each aimed at the different mechanisms of Alzheimer’s. It is interesting to note that there are still clinical trials underway that are testing drugs that act on Aβ when current research is leaning toward the conclusion that Aβ may not be one of the deep-seated causes of Alzheimer’s. Is a cocktail of medications that may not be treating a disease the best approach to treatment? Alzheimer’s research has come a long way, but there are still significant strides to be made. With improving technology and more research being conducted, hopefully the underlying cause of Alzheimer’s can be discovered and an effective treatment can also be found.
Insulin resistance?… Related to Alzheimer ’s disease? Who knew?
Usually when you think insulin dysfunction you think diabetes…not Alzheimer’s diseaseor dementia. Interestingly enough researchers have found a link between the two. As it turns out insulin may be linked to Alzheimer’s disease(AD) in more than one way. Below I will discuss the ways in which insulin resistance could be a risk factor leading to AD and
how diabetes ties in to the mix.
Image from: http://www.123rf.com/photo_9097816_old-hands-with-a-flower-on-the-black.html
What is insulin resistance?
First of all what is this so called condition of insulin resistance? It just means that the body produces insulin but for whatever reason the body cannot use it. Therefore the insulin is not doing all of its jobs that it’s supposed to do-most notably to help the body use glucose for energy. This leaves bloodstreams with elevated levels of insulin (hyperinsulinemia) and glucose(hyperglycemia). Insulin resistance can be caused by many interacting factors including excess weight, lack of exercise, and most importantly genetic make-up. For more information about insulin resistance please visit: http://diabetes.niddk.nih.gov/DM/pubs/insulinresistance/
How does this lead to Alzheimer’s disease?
Well the truth is we don’t exactly know yet. But from research that has been conducted so far we know that insulin resistance may be a strong indicator for people who are at the highest risk for becoming AD patients. Insulin is very important when it comes to cognitive function and aging. When insulin is being released but cannot be used by the body or brain, cell damage takes place. High abnormal levels of insulin can lead to increased risk of memory loss and brain cell degeneration such as AD. Over a long period of time the overabundant amount of insulin present in the brain becomes neurotoxic. This means that brain cells are being poisoned by these high levels of insulin. This can lead to the a poor functioning blood brain barrier (which plays a major role in brain protection) as well as insulin receptor dysfunction which ultimately puts people at high risk for AD.
Another important connection to make between insulin and AD is insulin’s relationship with the build-up of amyloid beta (Aβ) plaques. For you who are not familiar with Aβ plaques, they are formed by proteins that flock together and attach to brain cells and cause cell death. As of now Aβ plaques have been found in all AD patients. These plaques increase formation in the presence of high levels of insulin, which is initially caused by insulin resistance. The protein that breaks down these plaques is disrupted by high levels insulin and cannot do its job properly. So we get in large amount of plaques in the brain eventually resulting in AD or some type of dementia.
How can we prevent AD?
There are so many factors that lead to AD especially because insulin plays such a diverse role in the body’s metabolism. Genetics also plays a strong role in susceptibility and risk of AD. The best way reduce your risk, regardless of your genetic make up, is to stay active physically, mentally and socially while eating a healthy balanced diet. More healthy tips to reduce the risks of insulin resistance and can be found at: http://www.helpguide.org/elder/alzheimers_prevention_slowing_down_treatment.htm
How Old do We Want to Be?
This week’s topic concerns topics concerning insulin and Alzheimer’s disease deals largely with aging. Alzheimer’s is not alone with a strong correlation between age and occurrence. The chances of developing cancer and other major neurodegenerative diseases also greatly increase with age. There is little doubt that curing these diseases would led to an average extended lifespan in humanity along with improved quality of life, after all no one wants to feel the pain from cancer or forget what their children look like. These diseases dealing with life expansion seem to be “hot topics” in medicine as of late and have received much media attention. They bring a few questions to mind that I think are worth acknowledging. How far should medicine and research go with life extension? I believe that life extension is to a certain extent a by-product of well-practiced medicine and successful research but is there a limit to how “how far we go”? Or do we go with the school of thought that pursues life extension and higher quality of life.
The second question is perhaps more immediately relevant. There is only a fixed amount of money allocated from our government and other sources towards scientific research. Two categories which disease could be broken down into are those ages related mentioned earlier and the diseases acquired earlier in life for example down-syndrome. I think that cancer and these neurodegenerative diseases receive the attention they do because of their prevalence; they are much more common than obvious genetically debilitating diseases. Should our government be giving as much attention or funding as they do towards these diseases? Or should we be concentrating more on disease which affect our younger population?
Just another bullet point to the list of why we need to eat better and exercise!
- 25 million Americans have type II diabetes
- 16 million Americans will have Alzheimer’s disease by 2050
Did you know that two of America’s biggest health problems: Type II Diabetes and Alzheimer’s Disease, may be linked? On Sept. 19, 2011, NBC nightly news ran a news story about insulin being the “common culprit” between the two diseases. Check out the link below to watch the news story.
MSNBC video: study reinforces Alzheimer\’s/diabetes link
In Neurochemistry class this week, students looked more deeply into this possible link and raised some interesting questions. Why do we age? It turns out that signaling from insulin plays a role in causing “normal lifespan” – meaning we age. If there is a link between aging and age-related diseases such as Alzheimer’s disease, should we look at trying to slow down aging? What would this look like and what effect would that have on society? In addition, like the above story mentions, insulin signaling is involved with the formation of the amyloid-beta plaques that are the hallmark of Alzheimer’s disease. How exactly does insulin act and could we manipulate its actions to treat Alzheimer’s disease? Time will tell, but given the difficulty in this country to eat well and exercise, we may need to simply find a way!
