AGING

MODERN DISEASE PREVENTION

Your Subtitle text

Ava Gardner was the most beautiful woman in the world, and it's wonderful that she didn't cut up her face. She addressed aging by picking up her chin and receiving the light in a better way. And she looked like a woman. She never tried to look like a girl. —Sharon Stone

MANHATTAN BEACH PROJECT
He will wipe every tear from their eyes. There will be no more death or mourning or crying or pain, for the old order of things has passed away. Revelation 21:4
     During mid November in 2009 a conference of leading scientists, entrepreneurs, and anti-aging doctors was held in Manhattan Beach, California. The event was held to create real time lines and real budgets designed to completely change the face of human aging.
     The first scientific anti-aging conference was held during June 2000 in Manhattan Beach, California. It was no ordinary conference. Rather, it was a high-powered brainstorm session to figure out how to reverse aging. Just as the Manhattan Project was established in 1942 to build the atomic bomb to end World War II, the Manhattan "Beach" Project was founded on June 23rd, 2000 as an all-out assault on the world’s biggest killer—aging—at this scientific anti-aging conference.
     Twelve top researchers from around the world combined their genius and their levels of expertise in their specific specialties, and they laid the groundwork for what became a scientific roadmap for full age-reversal. Each scientist represented a separate discipline. Field’s such as stem cells, genomics, nanotechnology, information technology and more were represented.
     After years of ground breaking research, collaboration and advancement, scientists finally disclosed their plan to the public; a plan designed to start saving the 100,000 lives lost every day to aging and improve the quality and vitality of each new year added to everyone’s life.

Manhattan Beach Project Defined

Part 1: Sierra Sciences CEO William Andrews, Ph.D.

Part 2: Sierra Sciences CEO William Andrews, Ph.D.

Part 3: Sierra Sciences CEO William Andrews, Ph.D.

NOTE: William H. Andrews earned a Ph.D. in Molecular and Population Genetics in 1981 at the University of Georgia. While Director of Molecular Biology at Geron Corporation (1992 to 1997), he was one of the principal discoverers of both the RNA and the protein components of human telomerase. Shortly after his team at Geron Corporation successfully discovered and cloned human telomerase, Dr. Andrews founded Sierra Sciences. After this discovery, Geron decided to focus their efforts on developing telomerase inhibitors as potential cancer treatments. Dr. Andrews' focus on telomerase induction led him to split with Geron and subsequently found Sierra Sciences in 1999 to work on the development of a telomerase inducer.

CONTROLLABLE TELOMERASE GENE USED TO PARTIALLY REVERSE AGE-RELATED DEGENERATION
     Harvard scientists at Dana-Farber Cancer Institute say they have for the first time partially reversed age-related degeneration in mice, resulting in new growth of the brain and testes, improved fertility, and the return of a lost cognitive function.
     In a report posted online by the journal Nature in advance of print publication, researchers led by Ronald A. DePinho, a Harvard Medical School (HMS) professor of genetics, said they achieved the milestone in aging science by engineering mice with a controllable telomerase gene. The telomerase enzyme maintains the protective caps called telomeres that shield the ends of chromosomes.
     As humans age, low levels of telomerase are associated with progressive erosion of telomeres, which may then contribute to tissue degeneration and functional decline in the elderly. By creating mice with a telomerase switch, the researchers were able to generate prematurely aged mice. The switch allowed the scientists to find out whether reactivating telomerase in the animals would restore telomeres and mitigate the signs and symptoms of aging. The work showed a dramatic reversal of many aspects of aging, including reversal of brain disease and infertility.
     While human applications remain in the future, the strategy might one day be used to treat conditions such as rare genetic premature aging syndromes in which shortened telomeres play an important role, said DePinho, senior author of the report and the director of Dana-Farber’s Belfer Institute for Applied Cancer Science. “Whether this would impact on normal aging is a more difficult question,” he added. “But it is notable that telomere loss is associated with age-associated disorders and thus restoration of telomeres could alleviate such decline.” The first author is Mariela Jaskelioff, a research fellow in medicine in DePinho’s laboratory.
     Importantly, the animals showed no signs of developing cancer. This remains a concern because cancer cells turn on telomerase to make themselves virtually immortal. DePinho said the risk can be minimized by switching on telomerase only for a matter of days or weeks — which may be brief enough to avoid fueling hidden cancers or cause new ones to develop. Still, he observed, it is an important issue for further study.
     In addition, DePinho said these results may provide new avenues for regenerative medicine, because they suggest that quiescent adult stem cells in severely aged tissues remain viable and can be reactivated to repair tissue damage.
     “If you can remove the underlying damage and stresses that drive the aging process and cause stem cells to go into growth arrest, you may be able to recruit them back into a regenerative response to rejuvenate tissues and maintain health in the aged,” he said. Those stresses include the shortening of telomeres over time that causes cells and tissues to fail.
     Loss of telomeres sends a cascade of signals that cause cells to stop dividing or self-destruct, stem cells to go into retirement, organs to atrophy, and brain cells to die. Generally, the shortening of telomeres in normal tissues shows a steady decline, except in the case of cancer, where they are maintained.
     The experiments used mice that had been engineered to develop severe DNA and tissue damage as a result of abnormal, premature aging. These animals had short, dysfunctional telomeres and suffered a variety of age-related afflictions that progressed in successive generations of mice. Among the conditions were testes reduced in size and depleted of sperm, atrophied spleens, damage to the intestines, and shrinkage of the brain along with an inability to grow new brain cells.
     “We wanted to know: If you could flip the telomerase switch on and restore telomeres in animals with entrenched age-related disease, what would happen?” explained DePinho. “Would it slow down aging, stabilize it, or even reverse it?”
     Rather than supply the rodents with supplemental telomerase, the scientists devised a way to switch on the animals’ own dormant telomerase gene, known as TERT. They engineered the endogenous TERT gene to encode a fusion protein of TERT and the estrogen receptor. This fusion protein would only become activated with a special form of estrogen. With this setup, scientists could give the mice an estrogen-like drug at any time to stimulate the TERT-estrogen receptor fusion protein and make it active to maintain telomeres.
     Against this backdrop, the researchers administered the estrogen drug to some of the mice via a time-release pellet inserted under the skin. Other animals, the controls, were given a pellet containing no active drug.
     After four weeks, the scientists observed remarkable signs of rejuvenation in the treated mice. Overall, the mice exhibited increased levels of telomerase and lengthened telomeres, biological changes indicative of cells returning to a growth state with reversal of tissue degeneration, and increase in size of the spleen, testes, and brain. “It was akin to a Ponce de León effect,” noted DePinho, referring to the Spanish explorer who sought the mythical Fountain of Youth.
     “When we flipped the telomerase switch on and looked a month later, the brains had largely returned to normal,” said DePinho. More newborn nerve cells were observed, and the fatty myelin sheaths around nerve cells — which had become thinned in the aged animals — increased in diameter. In addition, the increase in telomerase revitalized slumbering brain stem cells so they could produce new neurons.
     To show that all this new activity actually caused functional improvements, the scientists tested the mice’s ability to avoid a certain area where they detected unpleasant odors that they associated with danger, such as scents of predators or rotten food. They had lost that survival skill as their olfactory nerve cells atrophied, but after the telomerase boost, those nerves regenerated and the mice regained their crucial sense of smell.
     “One of the most amazing changes was in the animals’ testes, which were essentially barren as aging caused the death and elimination of sperm cells,” recounted DePinho. “When we restored telomerase, the testes produced new sperm cells, and the animals’ fecundity was improved — their mates gave birth to larger litters.”
     The telomerase boost also lengthened the rodents’ life spans compared to their untreated counterparts — but they did not live longer than normal mice, said the researchers.
     The authors concluded, “This unprecedented reversal of age-related decline in the central nervous system and other organs vital to adult mammalian health justifies exploration of telomere rejuvenation strategies for age-associated diseases.”
     Other authors include members of the DePinho research group and Eleftheria Maratos-Flier, an HMS professor of medicine at Beth Israel Deaconess Medical Center. The research was supported by grants from the National Institutes of Health and the Belfer Foundation.
Richard Saltus. Partial reversal of aging achieved in mice. The Harvard University Gazette. November 28, 2010.
http://news.harvard.edu/gazette/tag/telomerase/, accessed November 30, 2010.

IT IS OK TO DIE
A new physician-written book sheds much-needed common sense on end-of-life care in the Emergency Department.
     Without reference to Pascal’s Wager or rehashing the Richard Dawkins/Francis Collins debates, let’s start with the premise – one constant we can all hold hands and sing Kumbaya about – that we’re all going to die. Where we go after death is a major debate, but this column has neither the space nor the inclination to carry on that fight. Despite the fact that we are no good in this country at talking about death, it is not going to go away any time soon. It awaits communists and capitalists, Muslims and Jews, people who run marathons and people who are getting fat and lazy sitting on the couch. Death is the universal invariant which sets the frame of reference for this experience which we are all sharing.
     All three of the major monotheistic religions which form the brotherhood of the children of Abraham put forth the notion that we will return to God, without qualifying it by our age at the time of such transmutation or the condition of the body. So I ask the question: Why are we the only modern western society which can’t let go? We beat the near dead like dogs. In fact if we did to our dogs what we are doing to our old infirm relatives we would be charged with animal cruelty.
     There are things I generally miss about not attending in the emergency department anymore. But one thing I don’t miss is pulling back the sheets on a nursing home transfer on a clearly end-stage patient whose family is demanding “everything” be done.
     What does “everything” mean anyway? I feel it is immoral to prolong suffering. If we can’t give meaningful life and import to a patient’s condition, what are we doing? Nobody ever said that the physician was under any legal or moral obligation to participate in this macabre dance of death. My personal experience since 1968 until now is that when the family was really spoken with they did not want to torture their dying relatives with unnecessary suffering.
     What really amazed me over the years was the fact that so few of them had actually been spoken to by their primary care doctor about what was going to happen to their loved one. Just as we teach families how to care for newborns we need to thoughtfully instruct them as to reasonable expectations at the end of life. When in doubt, at nursing homes, staff make the default judgment of having a near dead patient whisked away to the dernier cri of lights and sirens. This is Shakespeare’s “Full of sound and fury, signifying nothing” taken to the reductio ad absurdum.
     Since the United States economy is falling into the abyss of unconscionable debt, and the largest part of the rise in that debt is healthcare, we cannot avoid this debate.
     Thankfully, now enters a publication full of reason, ready to at least begin the proper debate – a consigliere in this sea of indecision. Monica Williams-Murphy, MD and her husband Kris Murphy have this month (January 2012) published a book called It’s OK to Die™.
     Monica is an emergency physician who, like the rest of us, has grown weary of going home after spending her shift dealing with end-of-life care issues and asking herself if we as a people have gone insane. Her husband Kris, though not a physician, is an intelligent tax-paying citizen who has watched this dance of death in his own family.
     As I was reading the book I wondered why I hadn’t written it myself. It’s so obvious, so clear, so full of exactly what each of us sees every shift in the department. It is not only the human story of what we do every day – how we feel as the “magicians” – but also the story of being caught in the middle between the suffering patient and the unprepared families. But I didn’t write the book, and thank God these two intelligent and sanguine people have. They confront the problem with insight and without animus. They have usurped thoughts we have all had and married them not just to introspection, but to an action plan.
     The book spends no time with useless bits of information and yet covers a broad array of topics – many of which are not usually included in medical texts. There is a must-read chapter entitled, “We agreed to let mom die,” in which the authors go through the problem with having multiple family members in the department and the various discussions that can go on as to whether advanced technology is going be used. Another must for physicians is the section which deals with the movement from high tech to “high touch” care. One needs to know that when God puts his hands on, you should take your hands off.
     This is not always clear in the heat of the moment in the emergency department. How do we make these decisions? How do we bring everybody along? How do we decide what type of technology will be used in the last moments of our life? The section on new directions of end-of-life care gets down into this nitty gritty. The book covers how to write orders on patients who are about to die, what should be included and what should be commented upon. How do we bring the nursing staff and other hospital personnel into meaningful alignment so that the goals of the patient and family are clear to us all?
     Another highlight of the book is the discussion on end stages and what the patient will look like and how to communicate these facts to the family. All the small details which are never really discussed in medicine become considerably more important when you’re dealing with the families of the near dead.
     There is a touching chapter entitled “Six things that must be said to make it OK to die.” Read it. Read it not as a doctor but as a person that has lost a friend or family member. It brought back memories of my own father’s death and how I could have done it better. By the time my mother died I had learned a lot. I wish I’d had some of the insights of this book to use with many of the families I’ve dealt with over the years. If you are counting on our salacious fourth estate to carry on this type of discussion, don’t hold your breath. These neebobs would rather comment on Bieber’s paternity or Kardashian’s gluteus maximus and consider these the important issues of our time.
     The kakistocracy we call our government has neither the intelligence nor the stomach for the translation of such debates into policy. So much for lawyers. No, if we want this done we must do it ourselves. If you are more than casually interested in the future of this society, help carry on the debate. Do not be dissuaded by the dilatory process which has been set up to thwart our long-term goals. To quote from It’s OK to Die™, “Medicine should be involved in 1) relieving suffering of the patient, 2) relieving unnecessary suffering of the families as they go through this horrific event, 3) to act as mindful stewards of the collective treasure of the United States.”
Greg Henry, MD. It is OK to Die. OH HENRY, Emergency Physicians Monthly. January 20, 2012. http://www.epmonthly.com/columns/oh-henry/it-is-ok-to-die/, accessed February 11, 2012.