Posted on 05/06/2017 5:36:19 AM PDT by LibWhacker
Even if a new drug proves to prolong human life, it won't receive regulatory approval for that purpose unless the FDA accepts that aging is a treatable medical condition.
David Sinclair has been reverse-engineering the aging process for two decades. As the co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School, Sinclair and his colleagues have identified several key enzymes and interactions inside cells that cause them to “lose their identity” over time, making our bodies more susceptible to diseases like cancer, heart disease, and dementia.
But what if aging itself is the real disease?
“Aging is the one disease that we all get if we live long enough,” Sinclair told Seeker. “I define it as a disease. Most doctors are trained that aging is something separate from disease. But the only difference in the medical textbooks is that if the majority of people get an age-associated disorder, we call it aging. If less than half of people get something over time, it’s a disease.”
Sinclair is part of a growing movement of “geroscientists” who believe that aging is not inevitable. What we once thought of as a natural process is in fact a degenerative condition — a condition that cannot be cured, but can in fact be slowed. With greater understanding of the molecular and cellular mechanisms of aging, they insist, we can delay the onset of age-related diseases, keeping us healthier longer.
Last week, Sinclair and a team of researchers from Harvard Medical School and the University of New South Wales announced the discovery of a molecule that significantly boosts a cell’s ability to repair damaged DNA. In a paper published March 23 in the journal Science, the authors describe how a molecule called NAD+ blocks a protein that inhibits the body’s natural ability to repair DNA.
"We’re not going to see people spend longer in nursing homes. We’re going to see them spend more time out of nursing homes.”
As we get older, NAD+ levels decrease, allowing DNA damage to build up. These mutations aren’t a direct cause of the progressive deterioration associated with aging, Sinclair said. “Cells cope with the damage by turning on the wrong genes at the wrong time,” he explained.
If NAD+ levels could be increased, Sinclair and his team hypothesized, perhaps the damage could be reversed.
They tested their theory on a group of older mice with low NAD+ levels. For a week, the mice drank a special serum of water mixed with NMN, a precursor of NAD+ that’s small enough to pass through the cellular wall. Once inside the mice’s cells, the NMN bonded with NMN molecules to form more NAD+.
“After just a week, we couldn’t tell the difference between the young mice and the old mice when we looked at their tissues,” said Sinclair.
Now Sinclair's team is moving toward human trials of the NAD+ booster, with the hope of getting a drug on the market within the next five years.
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“Our technology in the animals slows down the appearance of diseases, and that’s how we know that it’s slowing down aging itself. And as a consequence of being healthier, the animals live longer,” said Sinclair. “We think the same will happen in people. If we can delay all major diseases, then we will extend people’s lives, but only because they’re healthier. We’re not going to see people spend longer in nursing homes. We’re going to see them spend more time out of nursing homes.”
But even if Sinclair’s drug proves to delay the onset of age-related diseases in humans — effectively prolonging the human lifespan — it won’t be marketed as an “anti-aging” pill. That is, not unless the US Food and Drug Administration (FDA) accepts that aging is a treatable condition.
The FDA approves drugs for specific “indications” or recognized medical conditions. For example, the indication for a statin drug like Lipitor is cardiovascular disease, and one of the indications for Xanax is anxiety disorder. While the FDA approves drugs indicated for age-related diseases like cancer, type-2 diabetes, and dementia, it doesn’t recognize aging as its own indication... yet.
In June 2015, a group of scientists working under the American Federation for Aging Research (AFAR) met with FDA officials to make an ambitious proposal. Instead of approving a drug for one or two indications, they wanted the FDA to give their blessing to a clinical trial that would test a single drug’s effectiveness at preventing all of the major age-related illnesses at once: cancer, cardiovascular disease, dementia, and type-2 diabetes.
“We worked for weeks honing our arguments and our strategies for trying to convince them,” said Steven Austad, science director at AFAR and chair of the biology department at the University of Alabama Birmingham. “When we actually got into the meeting, within the first 15 minutes they said, ‘OK, that sounds good. Now let’s talk about the design of your study.’ We were kind of taken aback that they had accepted our logic so easily.”
“I think this is probably the most exciting thing to happen in aging research yet, and I think that’s going to be true no matter how the trial results turn out.”
Austad and his colleagues carefully avoided any mention of the words “anti-aging,” which they believe carry a whiff of hyperbole. Instead, they focused on making a sound scientific case for approving a “multimorbidity drug” that extends the so-called health span by delaying the onset of the most common age-related illnesses.
The drug in question is metfornin, a generic medication already approved by the FDA for type-2 diabetes. Metfornin has been taken by thousands of patients worldwide for decades and carries no side effects, except for a few unexpectedly positive ones. When researchers study people taking metfornin, they report startlingly lower incidence rates of cognitive impairment, cancer, and cardiovascular disease. And they live longer.
“By accident, metfornin seems to be a drug that affects most of the processes that we think are critical in determining how well or how poorly someone ages,” said Austad, including improved mitochondrial function, inhibition of free radicals, protection of DNA, and stimulation of something called the mTor pathway.
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The metfornin study proposed to the FDA, called Targeting Aging with Metfornin (TAME), would track 3,000 elderly participants over six years and collect detailed health data across a range of illnesses and conditions associated with aging. The trial will cost an estimated $66 million. AFAR is waiting to hear back about an NIH grant, and has a benefactor waiting in the wings with $35 million to cover any shortfalls.
“I think this is probably the most exciting thing to happen in aging research yet, and I think that’s going to be true no matter how the trial results turn out,” said Austad. “But if they turn out to be positive, then this is a game-changer in the health business.”
Austad envisions a day when older people take metfornin preventatively like a multivitamin.
“This has the potential of giving the average person another five to 10 years of healthy life,” he remarked. “Whether it will make them live longer remains to be seen. But even if it doesn’t, it will be a great advance if it were simply to shorten the period of ill health before the end of life. An extra five to 10 years of healthy life for the average person is huge."
Sinclair at Harvard Medical School also serves on the board of AFAR and is hopeful that the TAME trial will open the door for the FDA to fully recognizing aging as a disease.
“No question, that’s one the biggest things that this administration could do for medicine, to allow biotechnology companies to work toward [an aging drug] as a goal,” said Sinclair, who has co-founded several biotech companies of his own. “Right now, it’s not considered a realistic business model for that very reason. And if that were changed, the investment would go up exponentially.”
That was prior to the flood. Since that time God has limited our lifespan to 120 years. He knows what He is doing
I’m on the fence on this. Let’s accept that it’s possible to do this. A few of the implications of lifespans reaching 300 to 400 years are:
1. For humans, destined to live 400 years, the simple act of crossing the street would be dangerous. Many people would avoid all that and much of every kind of activity. This would greatly reduce the quality of life in all cultures and leave countries open to invasion and plunder(sort of already happening).
2. Jobs and careers would be held by Elders for centuries. Newborns would would have huge problems at age 20 of finding any worthwhile work. (Also sort of happening now ).
—— good grief—— I guess we are there now!
3. Overpopulation would require colonizing new planets to acquire additional resources and space.
Asimov wrote some science fiction regarding the issues that would arise with increased life-spans. 5 novels called the Robot series. (Robot Dawn, Caves of Steel, etc). A great summer read.
Science advances one funeral at a time...
A simple answer to this so called problem is to go back to allowing doctors to rx any FDA approved drug for any indication where the drug works, regardless of the FDA approval. The doctor can check to see if that drug has been approved in other countries and use their studies for his/her info base.
This restriction re not allowing doctors to rx any FDA approved drug for unapproved indications started during the LBJ years.
Those rules made FDA into a left wing controlled gate keeper of uses of any FDA approved drug. That enabled the University Medical Schools to be able to set up expensive clinical trials to approve the drugs for new indications. Many if not most medical schools are left wing controlled organizations.
This blocking of the use of non FDA approved indications has added billions of $’s to the cost of drugs that had been approved and doctors are aware of that drug’s side effect profile. A drug that might work for many indications is often restricted by FDA to only the original indication in the original NDA. (New Drug Application)
The answer is simple. Go back to days where legitimate real world doctors used a FDA approved drug for unapproved indications and presented their results to other doctors at meeting and via published papers.
With Google search and other search systems, a doctor with a patient with X disease could quickly search the data base of FDA approved drugs that have a positive treatment profile with non FDA approved indications.
Today, that doctor might be hammered for trying to help his/her patients by rxing a FDA approved drug for “an unapproved” indication. Many RX plans will not help pay for “unapproved” indications.
Last, but not least, the real world of patients getting an rx from their doctor is the best test of any drug re efficacy and safety. I would rather trust the results of hundreds or thousands of good doctors using X drug for any indication versus many Med School center’s studies.
It has at least one that's significant, if not recognized. It interferes with absorption of B12 and, IIRC, is reported to cause B12 deficiency in up to a third of folks on it. I was one. Happily that's correctible with B12 supplementation orally. If you've been on metformin, aren't taking B12 and haven't been checked get a simple B12 level test. B12 deficiency can cause anemia, or neurologic problems, if not recognized. Don't wait for the latter to learn you have it.
Is that a typo in the article or did they mean to say metfornin instead of metformin?
Exercise also helps. Been exercising religiously since age of 15 (50 years) and when home-rehab folks came in after my hip replacement (wore it out by running far enough to go around the world and then some) they told me that I wasn’t the typical 65 year old that needed their help doing the right exercises - they said I was “an apparent 50” in good enough shape to be as vital as the average 40 year old.
Yup, carbs are NOT an essential component of diet, your body can produce needed glucose from protein. The one thing they are good for is enabling certain special humans to feed and manage large numbers of others for directed activities like building pyramids and ziggurats (and modern equivalents) and then having them die off at the age where they become less economically useful.
Living 400, or 4000 years for that matter wouldn’t change my risk perception any. I’d just expect death to come during something I liked doing.
Being a geologist there’s a crapload of stuff I’d like to see/record that ain’t happening with 100 years but hundreds or thousands would make possible.
Also, in general, people would be in a lot less of a hurry if the time frame was stretched out. If you had a several thousand year lifespan when it came time to take a trip to the other side of the country walking with a pack or a cart is conceivable. People wouldn’t be in a frenzy to try to manage earning a living during their brief existence and fill their “bucket list” at the same time.
You could actually get a plot of land and undertake projects with decadal time spans (I’ll build a cabin here when these trees are mature in 50 years, these beavers will have this rocky wash modified into grazeable pasture in 70).
If we lived for centuries the impetus to jam all of the feelings and experiences we can into the brief window we currently have our physical and mental peak in would vanish (given a few decades to sink in). Most critically, we could uncouple ourselves from the shackles the “elite” have upon us by preying upon people’s general fear of death and desires to fulfill all of their experiential desires in their brief prime health window.
My grandmother lived to be 95, my mother is currently 92 and my MIL is 90.
I have no desire to be alive, with the lives the two living ones have.
My wife feels the same, btw.
Calling something a disease does not make it a disease.
Disease - definition - a disorder of structure or function in a human, animal, or plant.
Disorder - definition - to disturb (or a disturbance of) the [natural] order of something.
Since aging occurs in all life - human, animal, or plant, it must be assumed it is part of the natural order of life, and not a disease contrary to that natural order.
It may have a cause or causes, but to call any of them a disease is neither truth of science.
Can the natural order - aging and death - be delayed by things we can do, or things we can take that actually “disturb the natural order” such as to delay and/or reduce the aging process. Doing so still does not make aging a disease.
Being such a procrastinator as I am, I probably wouldn't get much more done in 4,000 years as in 40 anyway!
I dont’ know what your problem is, I knew it was cut and pasted. My point was that they misspelled the name of the medicine multiple times, not exactly something to inspire confidence in the information presented.
If I understand the mechanism correctly, it acts somewhat like a proper-diet-and-exercise in pill form; so we shouldn’t expect any life extension greater than what you could hope to get from the real thing.
You and I are - almost (see above stricken text) - on the same page here!
Those are exactly the same thoughts that occurred to me when I first began seriously contemplating this subject, 50-odd years ago.
Indeed, I, too, later drew parallels to those same Asimov novels. Asimov presciently describes the very social issues which would arise due to extreme longevity (though he attributes them instead to the effect of robots). In fact, I suggest that you now re-read those novels in this light, taking care to recognize the little clues and hints (and possible solutions!) which Asimov drops.
An extremely long-lived population would, indeed, be very risk-averse. Paradoxically, in spite of advanced medical technology keeping them at the peak of physical and mental fitness for an indefinite period, most individuals would be plagued by a perceived need for constant vigilence - always on the look-out for lethal hazards. Even only walking across the street could be viewed as an unnecessary risk (that's exactly the example I always cite). Of course, some people would adopt high-status thrill-seeking lifestyles.
On the other hand, due to the fantastic level of economic prosperity to be expected in the future, child-bearing would continue declining. Replacement levels would not be maintained - there would thus be no danger of overpopulation (on the contrary!).
Children (i.e., people under the age of 90 - who would not, however, actually be visibly distinguishable from oldsters) would then make up only a small percentage of the population. As a rarity, they would be viewed as a precious good, and have high status.
Due to the fantastic prosperity and technical advances, people would become very isolated. They would, also, increasingly turn to technology for the fulfillment of psychological needs (companionship). They would increasingly become unwilling and unable to form "normal" human attachments (resulting in a further decline in fertility). Catchword: "Bowling Alone."
To summarize:
A. Global population would actually decline.
B. Unemployment would be a non-issue, due to the immeasurable wealth of society. (Though you are correct in pointing out that many people would be unable to find gainful employment - though that expression will then be about as meaningful as "The divine right of kings" is today.)
All of that should sound quite familiar to us. All of these trends are visible today (as compared with, say, 150 years ago, when children were considered nuisances, to be seen and not heard; when it was expected that many would die from childhood diseases / not all would attain majority; when 20-year-olds were considered mature adults, and an unmarried, skateboarding 30-year-old would have been a laughing-stock; when white-haired 80-year-olds were regarded with reverence as fonts of knowledge instead of as technologically out-of-step, silly left-overs of a bygone time.
Interestingly, Robert A. Heinlein, who specifically addressed the topic of longevity in many of his novels, got it all wrong (with regards to the effects of said longevity on society as a whole)!
Regards,
My mom lived to be 94. I also have no interest in that existence. 80 will probably be sufficient.
When my body is worn out enough to preclude living independently, it’s time.
A lot of that later years “decrepitude” is allowing long standing habits and dietary trends to continue. You’ve got to keep pushing hard against the aches and the desire to eat like you did when you were 20, 40, etc... and get up each day and push yourself.
My dad had his .300 RUM accurized with a new process a little while back. While it shot crazy groups, it added a lot of weight and his comment was “it’s worthless now, I’m not humping that thing all over the Rockies hunting elk at my age (73 at time) so I got a .300 WIN mag...”. The note there being “humping a rifle in mountains at my age”.
I shoot with a lot of guys that are on the downhill side of the aging process and it’s a shame to see people, friends no less, that could easily look and feel 20 or 30 years younger if they could change some habits that they consider irrevocable at this point. I’m a believer, I merely dropped eating shitty foods (anything with added sugar, simple carbs etc) and it was a sea change.
The #1 thing a “modern” blood sugar load facilitates is inflammation and inflammation is the root for the vast majority of ailments of the older years. You decrease your inflammation state and the next thing you know you start wanting to do more, you do more and your attitude improves. It’s a positive feedback loop. While a certain small percentage of people will have underlying genetic problems that might not be amenable to this I believe the vast majority are subject to these improvements.
My mom is 100 and does real well, but she has a good attitude. I am not blessed with a sunny disposition so I generally want to live only ten years longer. I distinctly remember wanting to live to only 33. But that keeps being pushed out. Now at 62 I want to live to be no older than 75, but I have some projects that will take longer than that. So it will get pushed out, God willing. And my wife takes metformin.
Nobody believes me, but TM is the best thing for your psycho-physiology. People think I’m in my 40’s. Ha!:)
All the best to you and yours.
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