Saturday, December 4, 2010

Aging Is Dead

Updated January, 2017 after reading Fossel's "The Telomerase Revolution"

***

Introduction

Quietly, but with unstoppable force and increasing momentum, science is conquering the phenomenon of aging. Small battles have been chronicled over the last few years and the victor in this war has been clear to those with a scientific eye, but hard to fathom and harder still for the media to know what to do with. Is it just a far-fetched science item, the tiresome fountain-of-youth storyline? Or is it a phenomenon that could be the biggest story ever… one that will present social challenges that will make terrorism seem like child’s play? First the recent developments.

In the August 4, 2004 Philadelphia Inquirer, news was published of gene therapy that makes muscles stronger over the lifespan of mice. Days later a Reuters story reported that scientists have uncovered another part of the mechanism by which cancer spreads. The muscle story was relegated to the sports pages, yet muscle health is becoming more and more associated with overall health as we age. Muscle metabolism is one of the largest parts of our overall physiology and likely to have sustaining effects on many other parts of the body, starting with bones and ending with psychological well being. Muscle metabolism first caught my attention when writing "It's Not Carpal Tunnel Syndrome," now in its 11th printing (Amazon link).

As for cancer, it is arguably the keystone of the aging process. In his book, Why We Age, Steven Austad, explains that life is to a large degree the struggle to keep cancer at bay. Contrary to popular impression, it’s not just humans that get cancer—it destroys most animals if they live long enough. By my reckoning, cancer and aging are actually the same mystery. Thus the progress in this revolution is creeping up on us, hidden in articles labeled sports and cancer.

Staggering in its implications? Yes. Preposterous or wildly futuristic? Unfortunately not… not when you consider the following circumstances.

Proof

  1. Turtles live hundreds of years and trees thousands, so we’re only talking matters of degree, even if scientists only partly solve the mystery.

  2. Scientists have already mastered genetic engineering to the point where we need to distinguish “birth parents” from “genetic parents.”

  3. Animals have already been cloned and only politics and philosophy seem to be preventing the same for us. (What strange lingo will this bring forth? Are you the “natural instance” of yourself? You read it here first.)

  4. Biochemists tell us they’ve decoded the chemical recipe of life—human genes—in the Human Genome project. This information is being forged in the furnace of today’s computing lab. 

  5. Computer processing power has consistently doubled every 18 months! The theories and labwork have moved past the initial exploration phase into practical experimentation.

  6. Knowledge is doubling every ten years.




This blog is sponsored by PoopyPhonics, "The First Words on Your Kid's Mind." For a limited time, just send me an email and I'll send you a free copy. No shipping, no spam. —Jack Bellis




It's a fascinating mystery whether nature—natural selection/evolution, choose your term—by necessity pre-ordains death at some period after procreation... allowing us to sustain species, but deliberately preserving scarce resources? Is death tied to life by immutable logic inherent in biology? I think that the lifespans of turtles and trees proves otherwise. (Update January, 2017: Fossel's The Telomerase Revolution answers this: shorter lifespans probably encourage more agile adaptation to the physical environment).

The mystery of aging will fall, and very soon, much sooner than we are ready for.
Whenever I tell anyone that we will soon have to deal with living perhaps hundreds of years, the response is almost always one of dread. After all, they ask, who would want the decrepitude of old age prolonged at all, let alone indefinitely? But that is not the breakthrough I’m telling you to prepare for. I’m talking about the day in the not-to-distant future when scientists declare that they’ve completed unlocking the mystery of what makes cells get old. The next step will surely be a medical mechanism to stop that process… and we will be confronted with the question, at what age do you want to start taking the medicine? At what age do you want to stop aging?

There is one interesting exception, however. Our teeth won't hold up. They're the one (?) friction-bearing part that is not in a fluid construction. Dentistry will have to provide replaceable implants.

And what of the societal implications? Surely this would be mankind’s greatest dilemma, eclipsing--by far--such ethical issues as euthanasia and human cloning. Even if unlimited age doesn’t let us live as long as those multi-millenium redwoods, a mere two-fold increase would make our current population concerns laughable. Since I have no promising solutions to offer you, that’s one laugh you might want to enjoy now, before the difficult choices.

By the way, I have no particular optimism that they will ever figure out how to actually reverse your age. That would be wildly futuristic.

Jack Bellis, Originally written 2004


Timeline

  •  2014-May-9: WSJ Patient's Cells Battle Tumors This one is big... but of course we're on a track where each increment is simultaneously more microscopic yet more staggering. 
"It is based on long-standing observations that immune-system cells called T-cells often recognize tumors and travel to their locations in the body, but aren't plentiful or strong enough to kill the cancer cells. In the Science paper, researchers said they found a way to create enough useful T-cells to marshal a better attack. The researchers obtained a biopsy of one of Ms. Bachini's tumors, and in a process that took several weeks, sequenced its DNA and found a match between a mutation and certain T-cells from her body that reacted to the mutation. ... second treatment based on a biopsy from a different tumor, this time with 126 billion cells, 95% of them matched to the mutation. Her cancer responded almost immediately, researchers said.
"The daughter of Howard and Melanie Greenberg from Reisterstown, Md., Brooke is one of about a dozen children in the world who have what some call syndrome X -- a kind of Benjamin Button disorder that prevents them from aging." 
Apparently there are several cases of people who never advance past a young age, approximately that of a toddler. (I learned of this only in 2017, at which time this entry was added.) This would seem to be the opposite of progeria, where the aging switch is speeded up. In this disorder, the aging phenomenon seems to stop. But this is inaccurate... it's the development process that has stopped. Is this technically referred to as "maturation" or is that term reserved solely for the advancement of age beyond the peak vigor of the mid-twenties, where we are our strongest and healthiest?

  • 2013-JUL-26: Meaningful Markers of Aging (NYT). This article tells of progress in the isolation of genuine indicators of an individual's mortality pace: "Researchers at the University of North Carolina at Chapel Hill recently implanted a firefly gene into mice, engineering animals whose cells light up as they age and become “senescent,” losing the ability to divide and renew damaged tissue." An supporting my theme that the cures for cancer and aging are one-in-the-same, it adds this link to cancer: "...the research has shed intriguing light on cancer: The clock indicated that tumor cells have aged, on average, 40 percent more than normal cells taken from the same patients... The researchers also found that noncancerous cells near nascent tumors emitted a remarkably strong glow: early-stage cancers apparently set off hot spots of accelerated cellular aging."
    http://www.nytimes.com/2013/07/23/health/meaningful-markers-of-aging.html?_r=0
  • 2011-Dec-11: Milestone for Gene Therapy: Six Hemophilia B Sufferers Successfully Treated
    Using gene therapy, researchers have treated six patients with severe hemophilia B. When given a single infusion of gene therapy, patients with the inherited blood disorder showed an improved ability to form blood clots.
    http://www.smartplanet.com/blog/science-scope/gene-therapy-successfully-treats-hemophilia-b/11627
  • 2010-Dec-04: Aging Ills Reversed in MiceBy tweaking a gene, the researchers reversed brain disease and restored the sense of smell and fertility in prematurely aged mice. Previous experiments with calorie restriction and other methods have shown that aspects of aging can be slowed. This appears to be the first time that some age-related problems in animals have actually been reversed. The researchers had devised an estrogen-based drug that would switch on the animals' dormant telomerase gene, known as TERT. The drug, in the form of a time-release pellet, was inserted under the skin of some mice. A similar pellet without the active drug was given to a separate group of control mice. A month later, the treated mice showed surprising signs of rejuvenation. Overall, their telomeres had lengthened and the levels of telomerase had increased.
    Wall Street Journal Story
    Nature Magazine abstract

  • 2009-Feb-21: Small Antibodies—Nanabodies—from Llamas BetterScientists have established that antibodies from llamas are better than previous, larger antibodies: they can be combined and are more durable so they can be used orally. They are expected to be useful for blocking growth of cancerous tumors. Commercial products currently in the works. When a Llama Is Laid Back, It's Not the Only Beneficiary - WSJ.com
  • 2009-Feb-14: Evolution Link to Cancer
    Carlo Maley of Philadelphia's Wistar Institute tested a type of tumor called Barrett's esophagus, benign growths associated with acid reflux. He looked at tumor samples from a group of 268 patients and compared them with health histories taken over 81/2 years. He found the tumors with the most genetic diversity were most likely to become cancerous.
    http://www.philly.com/philly/news/homepage/39482342.html

  • 2008-Sep-03: Telomerase Decoded
    Scientists decipher a key part of cell telomerase, an enzyme that controls a cell's ability to multiply and plays an active role in at least 85 percent of all cancers. Just days after the previous event, this one might be a bigger blockbuster. I think it's huge.

  • 2008-Aug: Cell Converted to Another TypeHarvard biologists transformed one type of fully developed adult mouse cell directly into another inside a living animal, a startling advance that could lead to cures for a variety of illnesses. They pinpointed three crucial molecular switches that, when flipped, completely convert a common cell in the pancreas into the more precious insulin-producing ones that diabetics need to survive.

  • 2007-Dec: Artificial DNA
    Scientists have already built the world's first entirely handcrafted chromosome. Now researchers are poised to cross a dramatic barrier: the creation of life forms driven by completely artificial DNA. http://www.washingtonpost.com/wp-dyn/content/article/2007/12/16/AR2007121601900_pf.html

  • 2007-Nov: Stem Cell Creation
    Scientists convert regular cells to stem cells. Two unrelated teams manage to turn back the clock on cells, making them act like stem cells.

  • 2007-Nov: Genetic Supermouse
    Scientists genetically create supermouse... with extraordinary physical abilities ...eats up to 60 per cent more food than an ordinary mouse, the modified mouse does not put on weight. It also lives longer and enjoys an active sex life well into old age – being capable of breeding at three times the normal maximum age. The genetic alteration to a gene involved in glucose metabolism appears to stimulate the efficient use of body fat for energy production. At the same time, the mice do not suffer from a build up of lactic acid – which causes muscle cramps – a feature also seen in the best endurance athletes. They utilise mainly fatty acids for energy and produce very little lactic acid. They are not eating or drinking and yet they can run for four or five hours. They are 10 times more active than ordinary mice in their home cage. They also live longer – up to three years of age – and are reproductively active for almost three years. We could spot them at just a few weeks after birth. They popped around the cage like popcorn. We found that they were about 10 times as active as ordinary mice. http://news.independent.co.uk/sci_tech/article3121157.ece

  • 2007-Oct: Dramatic Cancer-Fighting Progress
    From Wall Street Journal Oct 18. Drs. Samuel Waxman & Richard Gambino report that three methods of cancer fighting are seeing dramatic accelleration of technological advance and results. Vaccines, epigenetics (protein targeting), and cancer "stem cells." This key phrase caught my eye: "...through the rapid expansion of computer databases of the genetic signatures of stem cells of different cancers..."

  • 2007-Jun: Moving DNA
    Scientists move DNA to related organism. Even if as non-scientists we can barely understand the precise terms of this latest hurdle crossed in genetic microscopy, the significance is not subtle: scientists took another step in manipulating the inner workings of the cell and its engine of life: DNA. They say "the first transplant of a synthetic chromosome into a cell could occur within a few months."

  • 2007-Mar: Stem Cell Ligament Growth
    Use of infants stem cells to grow new knee ligaments or elbow tendons.

  • 2006-Sep: Mice Anti-AgingMice without anti-cancer p16 gene kept healthy, young-looking organs filled with young looking cells even as they grew older http://www.npr.org/templates/story/story.php?storyId=5776986

  • 2006-Aug: Cell Regeneration Demystified
    Scientists discover stem-cell answer to how worms regenerate Short story(STLToday) Longer story (Phila Inquirer) The most significant fact in this development is the mention that scientists have only had the tools to examine this level of detail for 10 years! The implication is that we are just getting started and we've already discovered the potential for eternal regeneration.

  • 2004-Nov: Hormone supplements... testosterone cream, oral DHEA, HGG show promise for symptomatic anti-aging.

  • 2003-Sep: Resveratrol extends yeast cell life by 80%

  • 2003-Aug: Muscle strength extended in mice
  • 2000: Telomerase Restores Dermal Integrity to in Vitro-Aged Fibroblasts in a Reconstituted Skin Model
    "...telomerase activity not only confers replicative immortality to skin fibroblasts, but can also prevent or reverse the loss of biological function seen in senescent cell populations."
     Experimental Cell Research Volume 258, Issue 2, 1 August 2000, Pages 270-278
  • 1998: Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
    In contrast to telomerase-negative control clones, which exhibited telomere shortening and senescence, telomerase-expressing clones had elongated telomeres, divided vigorously, and showed reduced staining for β-galactosidase, a biomarker for senescence. Notably, the telomerase-expressing clones have a normal karyotype and have already exceeded their normal life-span by at least 20 doublings, thus establishing a causal relationship between telomere shortening and in vitro cellular senescence. The ability to maintain normal human cells in a phenotypically youthful state could have important applications in research and medicine.
    http://science.sciencemag.org/content/279/5349/349.full 

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