Is Castration the Answer to Longevity?

Genetic studies by Cynthia Kenyon—at the Hillblom Center for the Biology of Aging at the University of California San Francisco—with flatworms, and Richard Miller—at the Geriatrics Center of the Medical School, University of Michigan—with mice, show that having a diminished growth hormone production (or reception) seems to increase longevity. Having stunted growth increases longevity. The body seems to know that it needs to live longer to pass on its genes since its growth is stunted.

Which is exactly what happens with Michael Rose’ s experiments—at the Department of Ecology and Evolutionary Biology at the University of California, Irvine—with flies. Collecting eggs produced by older mothers produces offspring that lived longer.

There seems to be an expiration date stamped on 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.  The best way to explain this is through the disposable soma theory. This theory which was first developed in 1977 by a biologist named Thomas Kirkwood—who now heads The Institute for Ageing and Health in its School of Clinical Medical Sciences, at Newcastle University—states that the body protects itself just enough so that we are able to pass on our genes.

What if we cheated our body? As in these experiments cheating the body into thinking that it is developing really slowly and therefore needed more time. What if we were castrated? The Cumming Manuscript Collection of the New York Academy of Medicine Library contains more than 1200 references, abstracts, and documents concerning the early history of human castration.

But the first time that eunuchs—boys who had their testicles and sometimes their penis removed surgically—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—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 about hormones. Voronoff gained fame for his technique of grafting monkey testicle tissue on to the scrotum of men for anti-aging purposes. Voronoff and his predecessor and mentor Charles-Édouard Brown-Séquard—although ridiculed at the time—developed the field of endocrinology, the study of hormones. 

Coming back to the observation about eunuchs, Voronoff observations was that castration had retarding effects.

But then a new study in 2012 by Kyung-Jin Min from the Inha University, and his Korean colleagues, reversed this finding. In their study the 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.

Historically, and as recent as the 19th century, eunuchs were common across the world. Castrati boys—castrated before puberty—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 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 called 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 The emperor maintained approximately 2,000 in his service, the imperial princes and princesses each had about 30, and various family members were allowed 10 or so eunuchs each. Although in this context, castration was mostly as a punishment, 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.

In 1999 Jean Wilson and Claus Roehrborn investigated the long-term effects of castration. These included the enlargement of the pituitary gland, especially among those with an earlier castration. Skeletal changes included thinning of the bones of the skull and decreased bone mineral density. Although an increased incidence of fractures does not appear to have been reported in the eunuchs. 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 life span differed in their study.

A study on life span difference was done earlier in 1969, by James Hamilton and Gordon Mestler from the Department of Anatomy, State University of New York College of Medicine. They studied the mortality of patients in a mental institution with a population of 735 intact White males, 883 intact White females, and 297 White eunuchs. It was common practice to castrate mentally challenged children at the turn of the century, part of the eugenics movement. 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 ago, or even 100 years age. In most cases it was a very violent world where men suffered early mortality through wars, famine, and daily trauma.  Eunuchs, because of their demeanor might have escaped all of that onslaught of violence. They might also have had more nurturing qualities that extended to looking after themselves better. We will never know.

Pragmatically we know that sex, and the activity surrounding sex, increases longevity. Howard Friedman and Leslie Martin in the Longevity Project longitudinal study provided our first glimpse into female orgasms and longevity. The study which was begun by Lewis Terman of Stanford University, California in 1921 on 1548 children with high intelligence born around 1910 was continued after his death in 1958. 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 in six small villages about their sexual frequency,, then followed up on their death records ten years later. The authors 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 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. In some cases they also carried out extra marital affairs.

Perhaps there are better ways to cheat the body to tell it that it is not quite finished yet. Perhaps if you behave like you are still sowing seeds, the body will still support your endeavors. It is likely then that you do not need to cheat the body. It seems that enjoying its great capacity, in all its wondrous glory, is enough to increase longevity. Castration might cheat the body to stay around longer, but sex will make it want to stay longer. 

© USA Copyrighted 2014 Mario D. Garrett

Grieve Alone, Your Way.

Despite older adults having more experience with grief, the classic grief study that has determined grief counseling was developed for children.

Most everyone knows of the Swiss physician Elizabeth Kubler-Ross stages of grief. Based on earlier work by the psychologists Bowlby and Parkes, Kubler-Ross crystalized the stages in her 1969 book On Death and Dying. What was unique is focusing on communication during grieving. She singlehandedly overturned how physicians were treating dying patients—as medical failures to be ignored until they expired. 

The theory states that we go through a series of stages before we come to accept the loss. Kubler-Ross defines five stages starting with an initial short period of Denial (D) that it could not happening, moving into Anger (A) when the loss is taken personally, followed by a series of Bargaining (B) strategies to try and reverse the outcome, and then once the realization of the loss is seen as permanent, Depression (D) and eventually, at the end of the grief there is Acceptance (A) that we cannot change these events. DABDA model of stages of dying morphed into stages of grief.

It is the only grief theory discussed in psychology training. The stage theory of grief is also part of the medical curricula and part of the grief education at the National Cancer Institute.  It has been accepted widely across the globe. It is the script provided to grieving relatives and has even entered into product market research to understand the reaction to the “death” of iPhone 4 in favor of iPhone 5.  It is a pervasive theory.

Despite its popularity, how accurate is it for older adults?

George Bonanno with Columbia University, New York, has been the main counterpoint for these stages.  Bonanno takes a diametrically apposing approach.  He argues that there are no stages. In fact having no stages is healthy. In 2002 Bonanno studied elderly bereaving spouses and nearly half showed no signs of shock, despair, anxiety or intrusive thoughts six months after their loss. This he termed as Resilience. Suggesting that grief stages are not prescriptive, dispelling "grief work hypothesis."

This idea of expressing grief in order to cope was also dispelled by the Dutch husband-and-wife Dutch research team Wolfgang and Margaret Stroebe of Utrecht University. They found that widows who avoided confronting their loss were not any more depressed than widows who "worked through" their grief—talking or writing about the experience. More recently, in 2008, Mark Seery from State University of New York and his colleagues studying reactions to the attacks of September 11, 2001, reported similar findings. There are no stages. It is not prescriptive to healthy coping.

But what these stages have done is that it allowed grieving to be accepted as healthy. It is the first time since Victorian times that grief is validated. Because there were assumed stages, people felt more comfortable to allow others express their grief—thinking, this is only a stage, it will pass. Although there are many valid criticisms, focused on the meaning of constructs and the therapeutic value of expressing loss, one outcome has been that we are discussing grief. And that is healthy, because grief is real and painful.

 © USA Copyrighted 2014 Mario D. Garrett

Grieve Alone, Your Way.

Despite older adults having more experience with grief, the classic grief study that has determined grief counseling was developed for children.

Most everyone knows of the Swiss physician Elizabeth Kubler-Ross stages of grief. Based on earlier work by the psychologists Bowlby and Parkes, Kubler-Ross crystalized the stages in her 1969 book On Death and Dying. What was unique is focusing on communication during grieving. She singlehandedly overturned how physicians were treating dying patients—as medical failures to be ignored until they expired. 

The theory states that we go through a series of stages before we come to accept the loss. Kubler-Ross defines five stages starting with an initial short period of Denial (D) that it could not happening, moving into Anger (A) when the loss is taken personally, followed by a series of Bargaining (B) strategies to try and reverse the outcome, and then once the realization of the loss is seen as permanent, Depression (D) and eventually, at the end of the grief there is Acceptance (A) that we cannot change these events. DABDA model of stages of dying morphed into stages of grief.

It is the only grief theory discussed in psychology training. The stage theory of grief is also part of the medical curricula and part of the grief education at the National Cancer Institute.  It has been accepted widely across the globe. It is the script provided to grieving relatives and has even entered into product market research to understand the reaction to the “death” of iPhone 4 in favor of iPhone 5.  It is a pervasive theory.

Despite its popularity, how accurate is it for older adults?

George Bonanno with Columbia University, New York, has been the main counterpoint for these stages.  Bonanno takes a diametrically apposing approach.  He argues that there are no stages. In fact having no stages is healthy. In 2002 Bonanno studied elderly bereaving spouses and nearly half showed no signs of shock, despair, anxiety or intrusive thoughts six months after their loss. This he termed as Resilience. Suggesting that grief stages are not prescriptive, dispelling "grief work hypothesis."

This idea of expressing grief in order to cope was also dispelled by the Dutch husband-and-wife Dutch research team Wolfgang and Margaret Stroebe of Utrecht University. They found that widows who avoided confronting their loss were not any more depressed than widows who "worked through" their grief—talking or writing about the experience. More recently, in 2008, Mark Seery from State University of New York and his colleagues studying reactions to the attacks of September 11, 2001, reported similar findings. There are no stages. It is not prescriptive to healthy coping.

But what these stages have done is that it allowed grieving to be accepted as healthy. It is the first time since Victorian times that grief is validated. Because there were assumed stages, people felt more comfortable to allow others express their grief—thinking, this is only a stage, it will pass. Although there are many valid criticisms, focused on the meaning of constructs and the therapeutic value of expressing loss, one outcome has been that we are discussing grief. And that is healthy, because grief is real and painful.

Are we Suppose to Live Longer?

The late Sherwin Nuland in his 1995 book How We Die described the process of extreme old-age death very eloquently: “Whether it is the anarchy of disordered biochemsitry or the direct result of its opposite-a carefully orchestrated genetic ride to death-we die of old age because we have been worn and torn and programmed to cave in. The very old do not succumb to disease-they implode their way into eternity.”

The most persuasive argument for the biology of death is the Hayflick Limit. In 1961, going against the thinking at the time, biologists Leonard Hayflick and Paul Moorhead noticed that their cell cultures were dying after replicating a certain number of times. At the time Alex Carrel—a Nobel prize winner in surgery—held the thinking at that time, that cells are naturally immortal. We do bad things to them to kill 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% oxygen—which is the same as human internal conditions—before stopping replicating.  Refuting the idea that normal cells are immortal. The mechanism was not yet known at the time of this observation. But a Russian scientist Alexey Olovnikov hypothesized in 1971, and later confirmed in 1984 by  Nobel prize winners Elizabeth Blackburn and Carol Greider for the necessity of proteins called telomeres at the end of the DNA which get shorter with every division until they get too short to allow for more replication.

Although this is an eloquent theory, there is large variance in correlating telomere length with aging. The telomeres are not proportional to longevity. Nuno Gomez from the University of Texas Southwestern Medical Center and his colleagues, undertook the largest comparative study involving over 60 mammalian species, reported that telomere length inversely correlates with lifespan, while telomerase (an enzyme that promotes the growth of telomeres) correlates with size of the species.

Assuming human fibroblasts endure 70 divisions—as Hayflick says in his 1994 book How and Why We Age—there are more than enough cells for several lifetimes. Biologically it is feasible that individual cells in our body can maintain their level of division  and renewal for at least 150 years. And yet no one has lived beyond 122 years.

In addition, it seems that telomeres do not provide us with a complete picture.  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 quickly, perhaps we started with fewer stem cells, or perhaps the environment that we live in degraded them faster.

Older people are more likely to have experienced more environmental stressors that damage stem cells, and utilized more of their stem cells. Once they run out or become disabled, stem cells cannot be replaced.

And then this might be the symphony that Sherwin Nuland talks about.  Because dying cells secrete chemicals that disrupt other cells in their immediate environment even a small percentage dying cells, can have a much broader domino effect on neighboring cells. There is a tipping point before an implosion into eternity.

 © USA Copyrighted 2014 Mario D. Garrett

How Old Are You?

Just under 11 years old should be the answer. Seriously. Biologically our body averages about 11 years old.

Jonas Frisen, a stem cell biologist at the Karolinska Institute in Stockholm developed a method for determining the age of each organ. Although some cells remain with us the duration of our life--neurons of the cerebral cortex, cells of your inner lens in our eyes, muscle cells of your heart—the rest of our body is in a constant frenzy of change and rejuvenation.

Even our brain changes and renews itself. Joseph Altman first discovered brain cell regeneration—or neurogenesis—in 1962. Recently Elizabeth Gould of Princeton Unviersity, reported that each day's memories might be recorded in the neurons generated that day. Our brain might be going through daily renewal and change. With white matter in the brain—the predominant matter—renewing itself faster then the grey matter—which just covers the surface of the cortex. While all these changes are going on in the brain everything else is changing and renewing itself.

The youngest part of our body is our intestines that are only 2-3 days old, while our taste buds replenish themselves every ten days. Then within weeks, our skin and lungs completely replenish themselves (2-4 weeks). Every few months our liver is replaced (5 months) and nails (6-10 months). The every four months, after travelling over 300 miles and going through the heart 170,000 times, 60 times per hour our red blood cells are given respite and are renewed.

Our annual makeover includes new hair (for those that have hair, every 3-6 years) new bones (every 10 years) and lastly, most of our heart (every 20 years).

So the question is why do we look so old if we are only 11 years old?

This is the central question in gerontology. As we renew each organ in our body—and we chronologically age—the rate of change decreases and we get more errors in new cells. There are many possible reasons for this, and all could apply. It could be that our genetic material gathers faulty changes and its information becomes gradually degraded. Like a cassette tape that is repeatedly copy.

It could also be because the cells themselves becomes less efficient at cleaning after themselves leaving behind them a lot of cellular trash. It could be that our stem cells—that exist even in older adults—eventually become less efficient with age as they are bombarded with toxins, harmful rays and temperature changes. Sometimes when we damage an organ—for example damaging our lungs by smoking—the scaring tissue cannot be renewed and replaced. We in effect stop our body from staying young.

This is why looking younger also means that you are younger and live longer. In the Danish Twin study Axel Skytthe and his colleagues reported that among monozygotic twins who share the same genes—the twin that looked younger is more likely to live longer. But there are no short cuts. Undergoing plastic surgery does not result in longer life because there is also the Hayflick Limit…each of our 30 trillion cells in our body has a time bomb. At some point the cells reach their own individual lifespan and stop reproducing.  

 © USA Copyrighted 2014 Mario D. Garrett