iAge

Friday, March 27, 2015

Genetics of Longevity

The most persuasive argument for the genetic influence on lifespan is the different lifespan of species. The best explanation we have of this absolute and static lifespan is the concept of the Hayflick Limit—a genetic program that kills cells. In 1961—going against the thinking at the time—biologists Leonard Hayflick and Paul Moorhead noticed that their cell cultures were dying after replicating (mitosis) a certain number of times. But during this period Alex Carrel—a Nobel Prize winner in surgery—held the thinking that cells are naturally immortal. We do bad things to them to them. Taking a direct leaf from the biblical story of Adam and Eve, we are held responsible for our own mortality. In contrast, Hayflick demonstrated that normal human fibroblasts cells divide about 70 times in 3 percent oxygen—which is the same as human internal conditions—before stopping replicating. This stopping of replication has become the Hayflick Limit. Refuting the idea that normal cells are immortal and establishing a biological basis for lifespan—the Hayflick Limit has established itself as the primary theory of what determines human lifespan.

The mechanism was not yet known at the time of this observation. But in 1971, a Russian scientist Alexey Olovnikov, hypothesized the involvement of the end caps of the DNA that controlled this Hayflick Limit. Elizabeth Blackburn and Carol Greider—who won the Nobel Prize in Biology for their studies—later confirmed this in 1984. They found evidence of proteins called telomeres at the end of the DNA which get shorter with every division (mitosis) until they get too short to allow for more replication. This telomeric theory identifies the mechanism of how the Hayflick Limit exists.

Although this is an eloquent theory, there is large variance in correlating telomere length with aging and with lifespan. Firstly, telomeres are not proportional to longevity. There are three main arguments against using telomeres as the sole explanation of lifespan. Nuno Gomez from the University of Texas Southwestern Medical Center and his colleagues, undertook the largest comparative study involving over 60 mammalian species, and they reported that telomere length inversely correlates with lifespan. They also found that while telomerase—an enzyme that promotes the re-growth of telomeres—correlates with size of the species. The larger the species, the more telomerase, and therefore there is more maintenance of telomeres. In addition, it seems that telomeres do not provide a complete understanding of lifespan. The second argument against the telomeric theory of lifespan comes from the Italian biologist Giuseppina Tesco and her colleagues in 1998—refuting earlier studies—found that fibroblast taken from centenarians showed no difference in the number of replications compared to cells from younger donors. It could be that within the body, cells can be replaced with new ones—rather than simply renewed.

Adult stem cells have been identified In many organs and tissues of older adults, including brain, bone marrow, peripheral blood, teeth, heart, gut, liver, blood vessels, skeletal muscle, skin, ovarian epithelium, and testis. They are thought to reside in a “stem cell niche" which is a specific area within each tissue. We all have these and yet some of us seem to use them up quicker, perhaps we started with fewer stem cells, or perhaps theenvironment that we live in degraded them faster. Older adults are more likely to have used up their supply of stem cell or experienced more stressors that damaged their stem cells. Once stem cells run out or become disabled, they cannot be replaced by the body. So there is also a limit for the utility of our endowed stem cells. The third argument comes from Leonard Hayflick himself, who observed that assuming human fibroblasts endure 70 divisions, there are more than enough cells for several lifetimes. So although the Hayflick Limit predicts that there has to be a lifespan—an upper limit to longevity—the evidence suggests that that limit could not have yet been achieved.

Aside from the genetic explanations of lifespan there is also the observable reality of demography—the study of changes and patterns in population. An earlier theoretical observation made by a British actuary Benjamin Gompertz was published in 1825. He observed a law of geometric progression in death rates as we grow older. The insight was a mathematical formulae which has the probability of dying doubling about every 7 or 8 years following puberty. This is known as the Gompertz curve and is constant in all observations of human (and most other species) mortality. The only modification to this curve is that it is shifting to the right allowing later—delayed—death mortality. This has been predicted through the rectangularization of this curve. While the decline at the end of life has been termed as the entropy in the life table. This theory argues that the Gompertz curve will be pushed up but that the lifespan will remain virtually unchanged, making a rectangular path. Under such a scenario, most people will live up to a maximum lifespan and then die. Until then, the life expectancy will increase but the age of death will remain virtually static and always below 122.

Some geneticists argue that we have not achieved the theoretical lifespan. As a consequence these scientists claim that we can increase the lifespan. There are many studies in this area but three act as seminal archetypes of the type of work being conducted.

The first type is a classic experiment by Michael Rose who began manipulating the life spans of fruit flies by allowing them to reproduce only at late ages. This forced researchers to pay attention to the survival and reproductive vigor of the flies through their middle age. The subsequent progeny of flies evolved longer life spans and greater reproduction over the next dozen generations.

The second type of experiment uses examples from nature, which they then emulated in the laboratory and involved growth hormones. At U.C San Francisco Cynthia Kenyon chemically knocked out certain genes in flatworms, the gene daf-2 which partially disables receptors that are sensitive to two hormones – insulin and a growth hormone called IGF-1. This mutation—which was original seen in nature and then replicated in the laboratory—nearly doubled the flatworms’ lifespan. These long-lived worms looked and acted younger than their control group, implying that extending the lifespan also extends healthy life.

Then there is the genetic observation with mice, in particular the work done by Richard Miller, and his infamous mouse called Yoda (who is now deceased.) Like other dwarf mice, Yoda had a natural genetic mutation that obstructs the production of growth and thyroid hormones. Dwarf mice tend to grow to only about a third the size of normal mice, which helps them live about 40 percent longer. There are three types of mice that share this longevity characteristic. The Snell and Ames dwarf mice have been bred to inherit mutations in Pit-1 and Prop1 genes, respectively, which disrupt the embryonic development of the pituitary gland. While the Laron dwarf mouse has a targeted gene deletion of either the growth hormone receptor (GHR-KO) or the growth hormone binding protein (GHBP-KO). So even though this mouse produces growth hormone, it is still growth-restricted because it is unable to respond to the hormone. The common denominator in all these mice is that they have stunted growth which correlates with increased lifespan.

Increasing the lifespan in all cases of genetic studies—manipulation or observation—is related to stunted growth or late life progeny. It has been argued that this delayed growth stamps an expiration date onto our genes. If we are stunted in growth or our parents delayed producing us, then our body seems to know that it needs to live longer in order to pass on its genes. There are two complementary theories that explain these observations.

The theory of Antagonistic Pleiotropy argues that some genes have contradictory effects at different age. Genes which might enhance your reproductive success—genes that increase testosterone in men, resulting in more muscle mass and masculine secondary sexual characteristics—may at the same time have detrimental effects on survival later in life—in testosterone example elevated risk of cancer. Natural selection tends to favor these kinds of genes because they maximize fitness, as higher mortality in the post-reproduction stage will have little impact on fitness compared to increased number of offspring. The second theory is the Disposable Soma Theory. This theory states that—given that there are finite resources to maintain and repair cells and organs, the body does a balancing act—the body protects itself just long enough so that we are able to pass on our genes. A similar argument is made by Leonard Hayflick to distinguish age related changes from lifespan who argues that longevity—whish is distinct from age changes—is indirectly determined by the genome.

Another area of research that compliments the genetic work on life span is the burgeoning research on Caloric Restriction (CR). Initially discovered in 1935 in mice, CR has been shown to increase the lifespan in yeast, insect, and in non-human primates. In humans CR is still undergoing testing, although initial results suggest prolongation of life as well as prevention of age-related are likely outcomes. The mechanism seems to emulate the genetic work of life prolongation, in that the CR elicits a hormesis event—a low level stressor that stimulates positive response where epigenetic switches are triggered.

As with all genetic work there are many confounders. From the genotype to the phenotype and then there is the environment. Even if we accept that stunted growth might improve lifespan, other factors might negate such gains. And that is the case with a southern Ecuador group where more than 250 individuals are thought to have Laron syndrome—IGF-1 deficiency in primary growth hormone—which is caused by a mutation in the growth hormone receptor gene with affected individuals growing to less than 4 feet tall. Although Laron patients appear to be protected against developing cancer. However, this apparent protection does not translate to a longer lifespan due to trauma and alcoholism. There is a schism between lifespan and theoretical lifespan…human behavior.

Lifespan

Lifespan is described by The Oxford English dictionary as “The length of time for which a person or animal lives or a thing functions.” Pragmatically, lifespan is defined as the period that the longest living member of a species has lived. Sometimes lifespan—or Maximum Lifespan—is used to refer to the longest period of time that a member of a species can live to. Scientists have not yet determined what the maximum length of time a human can live up to. This is an active theoretical field, and is home to lively speculation among some gerontologists. When it comes to humans, the oldest person that has ever lived defines lifespan. Verified by the Guinness World Records and the Gerontology Research Group, Jeanne Louise Calment, a French woman from Arles, lived to 122 years and 164 days. This lifespan remains the definition of human lifespan since her death in 1997.
In this regard, lifespan is an outlier—an extreme case of longevity. It is different from longevity, mean life span, average life span, life expectancy, individual lifespan, average age of death, average life expectancy and median age of death.
After the second World War, Max Klieber, a Swiss agricultural chemist, predicted that mass determines metabolism, and metabolism determines longevity. Larger animals tend to live longer. This theory has been elaborated in 2000 when a study that looked at nearly 4,100 longevity records of the highest documented age for a variety of fish, reptile, amphibian, bird, and mammalian species that included humans. There were four primary findings. First, longevity is positively correlated with body size between orders (e.g. the smaller rodents are shorter lived than the larger cetaceans) though not necessarily within orders—a biological grouping. As an example, longevity is not correlated with body size among seals and walruses. Second, animals that fly (i.e. birds and bats), or armored (turtles; armadillos) or live underground (moles; mole rats) tend to live longer than is predicted from body size alone. Third, there is great variance within species, so that lifespans vary by a factor of over 50 in mammals, herps and fish; and by over 15-fold in birds. Body size, metabolic rate, brain size all positively correlated with life span. Fourth, primates are long-lived mammals, the great apes (i.e. gorillas; chimpanzees) are long lived primates, and humans are extraordinarily long-lived great apes; human longevity exceeds nearly all other species both relatively and absolutely.
There is something uniquely human about great longevity, although it is not an exclusive characteristic of humans.
There are still some species that we have not yet observed a lifespan for. There are other species for whom we have not been able to observe mortality and therefore we do not have a lifespan for. There is a small jellyfish called turritopsis nutricula, that seems to regenerate itself from an adult back to an adolescent. A constant process of metamorphosis. These are also species that exhibit minimal aging. Kleiber’s Law was complicated by the work of Caleb Finch from the University of Southern California who—while researching aging among animals—found insignificant aging among rougheye rockfish (who can live up to 205 years), sturgeon (150 years for females), giant tortoise (152 years), bivalves and possibly lobsters. These included no observable age-related increases in mortality rate or decreases in reproduction rate after maturity, and no observable age-related decline in physiological capacity or disease resistance. Finch coined the term "negligible senescence" to describe very slow aging.
There have been three primary approaches to the study of lifespan; Genetic, Biological, and demographic using life expectancy and age of death. However, a new twist to lifespan studies emerged in a 2012 study by Kyung-Jin Min from the Inha University, and his Korean colleagues. These authors reported that during Chosun Dynasty between 14th to early 20th centuries Korean eunuchs lived 14 to 19 years longer than other (intact) men. Researchers were able to identify 81 eunuchs, who were castrated as boys, and determined that they lived to an average age of 70, significantly longer than other men of similar social status. Three of the eunuchs lived to 100. This is a centenarian rate that's far higher than would be expected today (one in 25,000.) Historically, but as recent as the 19th century, eunuchs were common across the world. Castrati boys—castrated beforepuberty—were among the most prized singers especially in catholic churches in Italy—the Sistine Chapel retained the last of the castrati singers—and Opera houses in Vienna. Elsewhere eunuchs were hired staff in harems and imperial palaces in Africa, China, Korea, Japan, and the rest of Asia and the Middle East. As well as in Europe and Russia.
In the 18th century there was a Christian sect called the Skoptzy, also known as the White Doves, whose male members—in order to attain their ideal of sanctity—subjected themselves to castration. They believed that the Messiah would not come until the Skoptsy numbered 144,000 (Rev. 14:1,4). Further East, in China, eunuchs played a more central role in government. Although in this context, castration was mostly apunishment, some subjected themselves to the procedure in order to gain employment. At the same time, during the Ottoman period, especially from the 16th century on, black eunuchs from Ethiopia or Sudan were in charge of the harem in the Ottoman court. Many of these boys were castrated at a monastery in Upper Egypt by Coptic priests. The practice was pervasive and endemic.
But the first time that eunuchs featured in longevity debates was with the observation by Serge Abrahamovitch Voronoff in the early 1900s. And it was not a positive observation. Voronoff—a French surgeon of Russian descent—worked at a hospital in Cairo from 1896 to 1910 where he had the opportunity to observe eunuchs. He noted their obesity, lack of body hair, and broad pelvises, as well as their flaccid muscles, lethargic movements, memory problems, and lowered intelligence. He concluded that the absence of testicles was responsible for aging and that their presence should prompt bone, muscle, nerve, and psychological development. He saw aging as the result of the lack of substance from the testicles and ovaries. This is all before we knew abouthormones. Voronoff gained fame for his technique of grafting monkey testicle tissue on to the scrotum of men to increase the lifespan. Voronoff and his predecessor and mentor Charles-Édouard Brown-Séquard—although ridiculed at the time—developed the field of endocrinology, the study of hormones. Voronoff observations was that castration had retarding effects. In 1999 Jean Wilson and Claus Roehrborn investigated the long-term effects of castration and concluded enlargement of the pituitary gland and decreased bone mineral density. There were also some reported growth of breasts in the Ottoman court eunuchs, which is also evident in photographs of Skoptzy men and Chinese eunuchs. Shrinkage of the prostate was common among eunuchs. However the authors could not resolve whether lifespan differed in their study. Such a study was done earlier in 1969, by James Hamilton and Gordon Mestler from the Department of Anatomy, State University of New York College of Medicine. In the turn of the 1900 it was common practice to castrate cognitively challenged children, a practice encouraged by the strong eugenics movement at that time. The study looked at mortality of patients in a mental institution with a population of 735 intact White males, 883 intact White females, and 297 White eunuchs. They reported that survival was significantly better in eunuchs than in intact males and females. This survival advantage started at age 25 years and continued throughout their life. The life expectancy for eunuchs was 69.3 years compared to 55.7 years in intact males. Males castrated at 8-14 years of age—before sexual maturation—were longer lived than males castrated at 20-39 years of age—after sexual maturation. Castration reduced the age of death by 0.28 years for every year of castration from age 39 and younger.
There are many changes that happen as a result of castration. The world was very different 600 years or even 100 years ago. In most cases it was a very violent world where men suffered early mortality through wars, famine, and petty violence. Eunuchs, because of their demeanor might have escaped that onslaught of violence. They might also have had more nurturing qualities that extended to looking after themselves better. We will never know.
What we observe in science tells us a very different story. Pragmatically we know that sex, and the activity surrounding sex, increases longevity. Howard Friedman in the Longevity Project longitudinal study provided our first glimpse into female orgasms and longevity. The study which was begun in 1921 by Lewis Terman of Stanford University, California looked at 1548 children with high intelligence born around 1910. Now in their nineties, the study morphed into a gerontological study. One of the interesting and pertinent findings was that women who had a higher frequency of orgasm tended to live longer than their less fulfilled sisters. No data on men was collected from this study. But a separate study in in the town of Caerphilly in south Wales, England, provided evidence for males as well. George Davey Smith from Department of Social Medicine, University of Bristol,, England, and his colleagues interviewed nearly 1,000 men about their sexual frequency, then followed up on their death records ten years later. The results determined that men who had two or more orgasms a week had died at a rate half that of the men who had orgasms less than once a month. And importantly there was a dose effect, where the more times these men had orgasms the longer they lived. These observations have been replicated in Sweden and in the USA for both male and female.

The most conclusive evidence on what promotes lifespan however comes from the masters of longevity themselves—centenarians. In the Blue Zones the cluster of centenarians teach us about the pragmatisms of living longer and sexual activity is a significant part of their life.

© USA Copyrighted 2015 Mario D. Garrett

Monday, December 29, 2014

Is Aging Determined by our Gut Bacteria?

Carolyn Bohach, a microbiologist at the University of Idaho estimates that there are 10 times more bacterial cells in your body than human cells. Although smaller than human cells, and weigh only 1-3% of our body weight, the 500-1,000 species of bacteria that inhabit our body have evolved with us for millions of years.

Although bacteria are all over our body--inside and out--we see how it maintenance balance particularly in the human gut. There are fewer physical changes in older adults' gastric system than any other system in the body. Although the stomach looses its elasticity and might be more prone to damage—primarily as a result of taking some medications—the small and large intestine, pancreas, liver, and gallbladder change minimally with age. So the changes that evolve inside our gut are argued to come from bacteria that inhabit this internal world.

In the gut there are 100 trillion microorganisms that engage in fermenting, killing off other harmful bacteria and viruses, enhancing our immune system and producing vitamins and hormones. This bacterial activity is so necessary to the body that their outcome, function as an independent organ--a virtual "forgotten" organ. Here, bacteria help extract energy and nutrients from our food. This sharing of benefits shows in experiments where bacteria-free rodents have to consume nearly a third more calories than normal rodents to maintain their body weight. Less well understood is the role of fungi and protozoa that are also part of the gut flora.

In 2012 Marcus Claesson and Ian Jeffery from University College Cork in Ireland and their colleagues, reported this gut flora changes among some older adults, and they correlated changes in the type of bacteria with frailty and mortality. They found that institutionalized older adults have a different gut flora than community older adults and younger people. And they related this flora—caused by a restricted diet—to diminished physical capacity.

But it was only in December 2014 that Martin Blaser from New York University and Glenn Webb from Vanderbilt University, Nashville, Tennessee, tried to explain how bacteria are designed to kill older adults. They argue that modern medical problems, such as inflammation-induced early cancer, resistance to infectious diseases and degenerative diseases are in response to bacterial change as we get older and this has an evolutionary cause. Using mathematical models the authors show how bacteria evolved because they contributed to the stability of early human populations: Enhancing the survivability of younger adults while increasing vulnerability of older adults. Such an evolutionary process has advantages, but in the modern world, bacteria's legacy is now a burden on human longevity. Although this mathematical model has many flaws—primarily the theory of antagonistic pleiotropy and that there are other factors other than bacteria responsible for specific diseases—it allows gerontologists to see aging as a balance, not an all or nothing event.

http://www.nih.govBacteria is necessary in balancing the biological activities in our human body. In one example scientists are using bacteria that cause botulism to eradicate tumors. While in another example, Linlin Guo and her colleagues from the Buck Institute for Research on Aging in California, have increased lifespan in flies by altering bacteria in their intestine. It seems that bacteria form an important system in the body which might have repercussion on our longevity. Our body is a universe of organic activity and we are still learning about this miracle.

© USA Copyrighted 2014 Mario D. Garrett

Monday, December 22, 2014

Reclaiming the word "Senile"

The other definition of senile is “pertaining to old age”. Senile is not “being demented.” That mistake comes from the earlier definition of dementia when in 1895 Arnold Pick identified premature dementia as separate from dementia of old people—senile dementia. Later of course, Emil Kraeplein defined Alzheimer’s dementia, which quickly separated old (senile) dementia from young (Alzheimer’s disease) dementia. But we still confuse “senile” with “dementia”.

The single most important factor that accelerates aging is negativity—our own and other people’s. In the blue zones we see people living past 100 years of age. Twenty years more than the average, nearly a quarter of a life more. What they do not have in these zones is negative stereotypes. Although stereotypes exist for everyone—race, gender, sexual preference, size, height, intelligence and even geographic residence—for older adults it is transient and develops fast and have little time to develop resilience.

Richard Eibach from the University of Waterloo, Ontario, Canada and his colleagues explained how older people internalize negative stereotypes. In one study the authors asked older adults to read text that had small type and low contrast. Some participants were told that the lack of clarity was due to a photocopying problem, while the rest received no explanation. Older adults that did not receive an explanation reported feeling 10 years older than the participants who had an explanation. And it is not just about feeling old but that they associated feeling old as a negative. Accepting the term “old” you accept an omnibus of negative stereotypes.

Thomas Hess and his colleagues from North Carolina State University in Raleigh, NC explored how stereotypes create a world of negative memes. There is a self-fulfilling prophesy. When older adults encounter negative stereotypes about age-related cognitive decline, their memory performance decreases, rate their own health as being worse than others, and rate themselves as lonelier. Stereotypes play a significant self-fulfilling role in diagnosis as well. Physicians who have been primed about the connection between memory loss and dementia—and it is now everywhere in the media—diagnosed 70% of their older adult patients who reported having memory problems, as having dementia rather than 14% when there was no stereotype.

And the stereotype does not have to be transmitted negatively. Even providing assistance while completing a puzzle—implicitly suggesting that they need help—resulted in decreased performance over time, whereas those older adults who were only provided with verbal encouragement showed increased performance over time. Don't let others patronize. Lets take over the concept of senile again. That pertaining to old age is not a negative. Be aware of accepting such negative judgments and of making them about yourself. We can reverse this process by starting with recognizing that senile does not have to be a negative term.

Saturday, November 29, 2014

Social Security: Supreme Court Denies the Fifth Amendment.

If I had to fix the country I would write the Constitution, as is, with all the Amendments. The Constitution is an amazing piece of legislation. The problem is that it has been diluted and reinterpreted to suit the current political flavor. The common assumption that the Supreme Court protects the Constitution is misplaced. Neither the Bill of Rights nor subsequent Amendments define the role of the Supreme Court as interpreting the Constitution. Despite this, the Supreme Court is about to change how we live and how we retire. Yes the Supreme Court will decide our fate especially in terms of how we benefit from our investment in Social Security.

Because there is no $2.7 Trillion "trust fund,” Social Security benefits have already started coming out of general funds. It will become untenable to continue to do so. And—as with the fate of the Affordable Care Act—the Supreme Court will make the final judgment. And we have a portent of how they will decide.

Already the Supreme Court has provided Congress with two views of what Social Security is: It can be either a social program or it can be an insurance program. And although these are mutually exclusive interpretations, the Supreme Curt made both judgments.

In 1960 the Supreme Court decided that Social Security is a social program. It denial benefits to a Bulgarian immigrant Ephram (Fedya) Nestor who came to the United States in 1913 until he was deported in 1965 because he lied on his citizenship application by not admitting that he was a member of the communist party at the time. Despite his continued contribution to Social Security for 19 years—since its inception in 1935--and despite that he was already receiving benefits he was deported and denied Social Security benefits. But his deportation, and subsequent denial of benefits, went beyond the 1954 deportation law. The fact that his second wife Barbara Nestor (nee Herman)—also a Bulgarian immigrant—was denied social security indicates that Social Security benefit payments are up to the whim of the state. The Supreme Court established the principle that entitlement to Social Security benefits is not a contractual right. Yale law professor Charles Reich famous 1964 article "The New Property"—in which he called Nestor "the most important of all judicial decisions concerning government largess"—urged courts to provide social security benefits the same protections as other property.

In the Nestor case the Supreme Court argued that Social Security was not insurance, and that "earned" social insurance benefits were neither "property" nor contractual right, a major pronouncement that has never been overturned—then came the story of an Amish farmer, Edwin D. Lee, and the Supreme Court flip-flopped. In 1982 the Supreme Court argued that Social Security is in fact an insurance program and not a social program.

Lee, who lived near New Wilmington, Pennsylvania, failed to withhold social security taxes from his employees or to pay the employer's share of such taxes because he believed that payment of the taxes and receipt of benefits would violate the Amish faith: "But if any provide not for his own, and specially for those of his own house, he hath denied the faith, and is worse than an infidel.” Timothy 5:8. Edwin Lee and the Amish do not object to paying taxes except for the Social Security and unemployment taxes. They protest these taxes, formally, on the grounds that they represent forms of insurance, which their religion prohibits.

Lee sued in Federal District Court for a refund, claiming that imposition of the taxes violated his First Amendment free exercise of religion rights and those of his employees. In passing this judgment, Chief Justice Burger argued that it “… is unconstitutional as applied to persons who object on religious grounds to receipt of public insurance benefits and to payment of taxes to support public insurance funds.” Clearly arguing that Social Security is an insurance program. A similar claim by a member of Sai Baba was denied exemption because although opposed to insurance on religious grounds, the faith did not provide for its members.

These two cases are important because they hold two divergent and exclusive interpretations of the law at the same time. Although there have been many other cases, the fact that these two judgments have not been reconciled has to be intentional. It allows Supreme Court to interpret the law to benefit the type of Congress that we have. When Social Security benefits can no longer be paid from the general fund, then there will be judgments on who and how much will benefit. Whatever the outcome, the Supreme Court has already decided that our benefits are not entitled nor guaranteed. We have to continuously make Congress accountable for the “trust fund” that we lost “trust” in and which has no ”funds.” The Fifth Amendment ends: “nor shall private property be taken for public use, without just compensation." All we need now is for the Constitution to be honored.

Saturday, November 8, 2014

Hiding from the Pain: Robin Williams's Autopsy

Robin Williams’s death on August 11 2014 generated a lot of interest because there were so many cues. Or cues that we strongly believe we need in order to be able to explain his suicide as “rational”. We are now learning that depression, anxiety, and Parkinson’s disease weren’t the only issues plaguing Robin Williams in the months before his death. According to a new autopsy and toxicology report his brain also showed signs of dementia. We have now “explained” the suicide as a biological fate accompli. Biological determinism. Dementia and Parkinson’s at the same time. What better reason to commit suicide.

But this is rubbish.

What neurologists think as the disease in the brain—the neuropathology—which in Alzheimer’s are the plaques and tangles—has never been validated. We see a lot of plaques and tangles in the brains of dementia or Alzheimer’s patients after they die. But there is not one study that shows that the plaques and the tangles CAUSE the disease. The same as a scab over a wound. The scab is an indication of a trauma, but it is not the trauma itself.

If we did an autopsy of you today it is very likely that you have some of the signs of dementia. In fact most older adults have these plaques and tangles. So much so that just under one in three of older adults have as much disease as those with dementia but without expressing the disease. And it is not just older adults who have these neuronal damage. A study on young victims between the ages of 26 and 30 reported that more than one in five already had early stages of the disease.

What is stranger still is the observation that there are people with dementia who do not have the disease in their brain. There is a famous long-term study conducted by David Snowdon looking at nuns. Snowdon was one of the first to report such cases. There are inconsistencies in how we are trying—but failing—to define the cause of Alzheimer’s disease and dementia in general.

Diseases of the brain are not all that distinct. Although we have given names to specific diseases these are not as distinct in real life as neurologist would like them to be. We talk about Lewy Bodies dementia as though it is distinct from Alzheimer’s, but in fact they are on a sliding scale…more likely to look like Alzheimer’s or Lewy Bodies. There is also the vogue to call all types of dementia “Alzheimer’s”. Even Alois Alzheimer himself, more than 100 years ago, was confused by the distinction. And we remain confused today. Most of brain diseases share similar neurological deficits. Whether these are the cause or an expression of an underlying disease has not been determined.

With Robin Williams’s death we have to stop looking for simple answers. There is no greater answer to be found in biology. Our biological body is a balance—it is not a digital machine. As with cancer—and we all have cancer—it is how the body manages to keep it in balance. It is not whether there is a disease, but how we control and keep it in check. Evidence of dementia is no evidence. It is after-the-fact excuses to rationalize an individual’s pain and suffering as legitimate without understanding the pain and suffering.

© USA Copyrighted 2014 Mario D. Garrett

Saturday, October 25, 2014

Is Cancer the Cure for Alzheimer’s disease?

In 2014 Ferrán Catalá-López and his colleagues from the University of Valencia in Spain reviewed the inverse association between cancer and neurological diseases including dementia. What they reported is that numerous studies have been showing that if you had one of these two diseases you are less likely to get the other. The first anecdotal evidence came more than fifty years ago when patients with Parkinson’s disease were reported to have a lower rate of cancers. More recently, this inverse relationship has also been documented for Alzheimer’s disease. In fact, this inverse relationships is most pronounced with Alzheimer’s disease and Huntington’s disease. While for cancer it is more pronounced for colorectal cancer and lung cancer.

If you have had cancer you are 50% less likely to get Alzheimer’s disease. While, if you have Alzheimer’s disease you are 60-70% less likely to get cancer. The same results do not exist for vascular dementia or Lou Gehrig's disease (ALS) and for some cancers such a melanoma, non-melanoma skin cancer and breast cancer.

There could be a number of reasons for this, and all could be working at the same time. It could be that once you are diagnosed with cancer or Alzheimer’s disease the focus of clinical care is on treatment and there might be less active interest in searching for additional diseases. However, this does not explain why it does not work with other diseases. It could be that the therapy for both diseases protects you from getting the other disease. Although plausible, it is unlikely. It could also be that the two diseases are separated by vulnerability in age and therefore if cancer kills you first you will not have the opportunity to get dementia. While being spared cancer you are then more likely get dementia. Although there are studies that dispel these arguments—some more conclusively than others—there is however a more subtle and persuasive argument.

There is a growing understanding of the chemical balance that is played in the body especially the process of generating energy for cells. The imbalance in this process—known as Glycolysis—of how the body converts sugar into fuel (pyruvate) for cells could be the balance that determines which of these two diseases you are likely to get. Too little fuel for cells—since neurons have such energy demands—and you get Alzheimer’s disease. Too much fuel, which feeds the erratic cells, and you get cancer.

Although this is an interesting avenue for biological and chemical research, there is an additional offshoot of this way of thinking…and that is the rejuvenation of the concept of homeostasis. That along a continuum of cancer or Alzheimer’s disease there is a balance. First described by Claude Bernard in 1865 and later coined by Walter Bradford Cannon in 1926, homeostasis requires three basis mechanisms. A sensor to detect changes, a mechanism that can modify that change, and a feedback connection between the sensor and a mechanism. The concept that homeostasis can determine Alzheimer’s disease has radical repercussions for psychologists because both the sensor and the mechanism can have psychological components. As an example, for the sensor being happy and content, tells the body that the system is in homeostasis, in balance while being stressed tells a different story. For the mechanism, being active, engaging and having tactile and sensory stimulation moderates and modulates our internal chemistry.

© USA Copyrighted 2014 Mario D. Garrett