By Robert Kane Pappas

Robert Kane Pappas and Dr. Aubrey de Grey

On April 25^th, Aubrey de Grey participated in a debate with Professor Colin Blakemore – neuroscientist and ex-head of the Medical Research Council, UK’s largest funding body for bio medical research – at Oxford University’s Sheldonian Theatre. The debate’s title was: “Resolved this house wants to defeat aging entirely” and was to cover the feasibility and desirability of bringing aging under medical control.

After watching the video of the debate; among other things, it strikes me that the title itself helps obscure the nature and process of the scientific research currently underway to extend healthspan, and by implication, lifespan.

The problem waxes ironic.  To a large degree, Aubrey became “famous” by uttering the following on camera:

“I’m claiming that the first person to live to a 1,000, subject of course to global catastrophes, is actually, probably only about 10 years younger than the 1^st 150 year old, and that’s quite a thought.”

On the one hand, Aubrey’s thesis is provocative and possibly true – but there is a downside to such a framing of the discussion. The viewer or reader reacts –

“What, 10 years after 150, what? A 1,000 years, people from the middle ages would be alive, what? Population, resources? Bombs? – Who wants to live that long, the world sucks now, ahhhhhhh….!” 

I personally observed similar reactions in a portion of the audience who watched my film “To Age or Not To Age.”

Professor Blakemore’s debate responses fell along the above lines, like an opposing pundit with several conventional wisdom talking points. 

But Aubrey’s prediction hampers what could be an intriguing discussion about trajectory of the scientific understanding and the advances.

When I first interviewed Aubrey De Grey several years ago, he used the phrase “aging trance” to describe people’s mental paradigm with regard to the phenomenon of aging. Although I didn’t feel the phrase was perfect, he made a valid point.

When you delve into the subject of extending human lifespan via the frame of people living a thousand years, all kinds of prejudices color what the questions are and how they are asked.  Blakemore raised concerns about neurological memory, how people would spend their time, human motivation, population.  He made the further point about the complexity involved, how a war on this or that disease waged 30 years ago still hasn’t produced a solution, stuff like that.  All somewhat true, but also misleading.

One simply cannot adequately probe the subject of future advances when that discussion begins from the point of view of a thousand years.  Firstly, the process itself is, by definition, incremental. Supposing what your memory would be like at 1,000, indeed one’s mental framework, is ludicrous.

Further, judging the speed of scientific advancement in the future by pointing to the slow pace of the past is a superficial analysis.  Scientists are asking questions that they couldn’t imagine 5 years ago.  Techniques for finding multiple needles in haystacks simply didn’t exist in the near past. What is more – and I think this is crucial – in the midst of huge complexity, scientists are finding nexus genes and nexus points which cause a cascade of downstream events.  In other words, if you intervene at the right spot in the right way, the vast complexities resolve themselves.

Then there is the idea unintended consequences. There are always unintended consequences. Are they always bad?  Is every mutation bad?

For his part in the debate, Aubrey didn’t give clear examples of feasibility or cite several recent advances.  There is much that is unknown; but, the questions being asked, and the thread of recent results derived from those questions is striking.  Moreover, simple observations about how quickly communication has changed (smart phones and the like) compel one to surmise that the integration and speed of scientific research will increase.

So, the discussion of this topic must be from the point of view of the moment at hand, not about the dim distance. Right now, scientists can extend the healthspan and lifespan of animals and humans through a combination of lifestyle changes, and by tweaking a couple of fairly well understood molecular pathways having to do with nutrient signally and cellular upkeep, particularly, the mtor and Sirtuin genes.  It is happening now. In the wings, new understandings about adult stem cells, cell signaling, senescent cells, DNA repair, mitochondrial function and the epigenome point to a vast horizon.

When we speak from the point of view of 1,000 years, it seems impossible that humanity won’t destroy itself by then. But then again, change is incremental but does happen. So maybe we won’t. 

A thirty minute version of  TO AGE OR NOT TO AGE will be screened at the Hawaii Institute of Molecular Education’s symposium on Cell Signaling, Inflamation and Aging in Las Vegas on Tuesday, June 5th at 10:15 am.  The symposium takes place over two days (Tuesday, June 5th and Wednesday, June 6th) at the Trump International Hotel Las Vegas, 2000 Fashion Show Drive.  The film will follow a presentation by Vincent Guiliano, Ph.D., on Death and Rebirth of Oxidative Damage Theory of Aging — About NRF2.  Dr. Guiliano will lead an anti-aging group discussion immediately following the screening.  For more information on this event, click here.

By Robert Kane Pappas

“The Low Hanging Fruit” 

When discussing aging interventions – slowing down the aging process – note that there are causal relationships between aging, age related diseases, health span and lifespan. 

To make a further distinction, the pace of the application of various breakthroughs can be broken down into a second hierarchy: think of it as an apple tree.  There is ‘low hanging fruit’ – interventions available now such as calorie restriction and exercise (lifestyle adjustments) and substances that either mimic that caloric pathway or affect several already largely understood nexus genes that interact with that pathway; or genes relating to the insulin receptor and immune response pathways. 

We can pick that low hanging fruit from the ground right now; influence these genes (SIR1, mtor, IGF-1, Foxo3) with compounds like rapamycin, resveratrol and curcumin – and, if you up regulate or down regulate them selectively, you can increase health span and lifespan to a modest degree say 5 to 20 years.

Why is there a range of 5 to 20 years? 

The amount of increase will depend on which segment of the population, and subgroups within those segments, you are speaking about.  To make a simple model – break the population into 3 groups: the first and third groups represent a relatively small percentage of the population who have a strong genetic predisposition to either live for a very long time or have a genetic mutation or other factors which will cause them to develop a life threatening condition early on. 

For the middle group, people who have average repair gene settings, the genetic component of lifespan is 20 to 25 percent. The low hanging interventions can influence their lifespan to a greater degree. There is much room for improvement by influencing this group’s settings. 

Though scientists estimate that lifespan is about a quarter genetically impacted, according to studies of twins etc;  Dr. Nir Barzilai of Albert Einstein College of Medicine, who headed the Centenarian study – and another scientist, Dr.Stephen Austad of the Barshop Institute for Longevity and  Aging Studies – make a further distinction about these population groups.

In the outliers, for instance, they say, – ‘people who live a very long time the genetic component of lifespan is far higher”.  In these individuals, the genes referred to above are already naturally in a setting that confers longevity.  These people either never get sick (many of Barzilai’s centenarians have smoked for 80 or even 90 years) or they always get better (their nexus repair genes are more active). And most of their close relatives live a long time. Thus for these outliers, the low hanging fruit is likely to have a modest effect on their lifespan, perhaps 5 years. The centenarians have a very square healthspan/lifespan graph – meaning that they stay active and healthy for the vast majority of their long lives – they have a short period of sickness and then they die. 

Dr. Leonard Guarente of MIT explained to me that his research would lead to a leveling of the population’s healthspan and lifespan; giving people who were not blessed with great gene settings a significant lengthening of health span and lifespan.  

How long? The guess, here in terms of the low fruit, is 10-20 years. And – it is not clear whether tweaking a number of these genes would have a cumulative effect. Probably not – because these pathways are largely overlapping – though there may be an additive affect. 

The near term economic and political impact of the extension of lifespan and health span is another subject. 

“The Middle Fruit Level” 

From here on it gets a bit tricky – much like predicting a storm more than 5 days in advance. Note well though, the storm is coming. 

The time frame estimate is that implementation of the next level, “the middle fruit” will begin within 10 years, though maybe not for the general public – and that too is another story.  

Within 10 years Big Pharma will have created patented analogues of compounds that influence these genes; approved by the FDA for various conditions.  The increase in lifespan will be a side effect. But – within that period – it will be impossible to prove this in human studies because (obviously) of the length of time involved. 

When you go to an apple orchard, you often see step ladders and extension poles used to retrieve fruit beyond a person’s reach. Over the past twenty years the molecular biologists have developed new tools.  For example, genomic mapping has gone from costing 100’s of millions of dollars to a couple thousand, and will soon cost 100’s. Coupled with the speed of modern computing and algorithms, scientists can address the higher level of aging research – that being extending lifespan/healthspan beyond the traditional wall of 120 years. 

Two questions: 

1- Why will they be able to do that? 

2- Do all the scientists think that? 

I will give short answers to each and then elaborate in turn. 

Addressing the former question – Scientists will be able to do this because the level of nature that needs to be intervened with does not conflict with evolution. Lifespan already increases 5 hours a day. Several scientists who I spoke with said that they were very surprised “just how easy it is to change lifespan.”   

This is not a breaking the speed of light level question. 

Stem cell reversal?  Smart M.D.’s are, themselves, shocked at what is suddenly possible with regard to stem cells – and we’re not talking about embryonic stem cells (a source of political wrangling) – we’re talking about taking a bit of your skin or blood or other cells, and reverting them back to a state of early development, where these cells can become (differentiate) into a younger version of that organ. 

Or, researchers have changed the environment (signaling) of a cell, say a muscle cell, and it has acted younger, become younger, on its own without surgery. And these cells and tissues are yours – not transplants – so there is no issue of rejection.  Moreover, these cells will at some point be able to be corrected for genetic defects.  So – if a heart muscle or some organ had a mutation – they will correct that mutation, and the replacement won’t be the lemon that person was born with. 

There are – by definition – always unintended consequences.  I will briefly address this issue when I speak of the fruit at the top of the aging tree. This level of discussion suffices for now. 

Within the middle fruit level, global cures for alzheimer’s and cancer will be developed. In part, the answers will have to do with mimicking the processes of organisms and animals that never get cancer – for instance – the naked mole rat.  Try as they will, scientists have been unable to give this animal cancer, no matter what they do. Naked mole rats have double P16 genes, this insures that cells don’t get too close.  Again, better versions of what we already have. They also live ten times longer than their close cousins. 

We’re not talking about having to grow wings in order to manage or cure cancer. There is a tribe in South America (they are very short) who have a mutation in their IGF-1 receptor.  They hardly ever get cancer.  So global cancer cures will have to do with piggy backing and delivering on what is now known.  

Delay aging and in most cases you delay or ameliorate virtually all disease including cancer. 

Cancer permanently turns on a gene called telomerase, making it immortal.  There is much research focusing on new therapies via telomerase manipulation. 

Controlling and alleviating cell senescence will be harvested on the second level of hanging fruit. This will impact both cancer, inflammation, and by extension, tissue aging itself. 

Research in mitochondrial biogenesis will impact the normally dwindling energy supply of the mitochondria, the power plants of our cells. 

Changing average Telomere length is still an open question in regard to whether it is a cause or an effect or both – vis a vis aging and lifespan; and its relationship to cancer is still not fully known. 

Dr. Stephen Austad discovered opossums who lost their predators. Over a period of time they developed longer lifespans, had an additional litter.  This suggests that genes and systems concerning the flight/fight response affect lifespan. 

What about the answer to the second question? 

“Do scientists think we can break the 120 year barrier in the near future?” 

I think that most do.  Some don’t. What is certain is that few will admit it – at least to the Mainstream News Media. 

A scientist can only ruin his career by saying so. Careers are never ruined by not opening your mouth, by playing it safe. I have found that the higher the scientific profile, the more conservative the public estimates. 

Because I am not a journalist I have heard things scientists don’t tell journalists. And I have seen them finesse journalists about issues – things they told me differently about off the record. 

This goes to how the media reports these advances; and that too is another subject, as is the relationship between government, research lab, biotech company and the drug companies – and its impact on the rate of progress. 

“The Fruit at the Top of the Tree”

At the third level of fruit the questions get weirder. 

Major issues set the backdrop for any discussion: 

     * Unintended consequences 

     * The speed of advancement. 

     * Do humans want to live indefinitely? 

     * The larger social and political and psychological  questions.  

These questions permeate all levels of fruit harvesting, especially for the public at large. My film series will address these factors – with regard to the various stages of the scientific application. 

“The speed of advancement” 

This question is addressed well by Aubrey De Grey Ph.D. He believes that very soon, perhaps 20 years out; we will begin to outrun aging.  The advances will outpace what is going wrong, and death due to aging and disease will become an indefinite thing. 

Actual age reversal was something – that, when I first heard of it 5 years ago – I put in the category of time travel and ghosts. 

But recent research into germ cells (babies are born at zero) and menopause reversal, creation of new eggs etc. says that this will be on the table in around 20 years. And then all bets will be off. 

The interfacing of nano technology, computer technology – with the organic will become an issue. 

“Unintended consequences” can be grouped into questions concerning genetic consequences, and to the larger global environment, from population and resource issues, to politics and religion.   

Without those questions being asked soon, we won’t survive long enough to reap the fruit of this new science. 

After 5 years of interviewing the researchers and poking around labs with my camera, it is not a question of if but when.  The general population has little idea of what is about to befall them.

by Robert Kane Pappas

I could probably find the script – lying somewhere down here in my basement office, the dungeon where I have been making films for a long time.  But the place is swamped with them so I’m not going to look.  I’ll just try to remember what I can. 

Cat Colvin, a woman I know, sent the screenplay to me to read and comment on – in, I think it was 2006 – her sister Marie Colvin was the author. Marie got blown up yesterday in Syria. 

It’s a feature film script. The main character is a woman Journalist, living with or married to a man in London, who feels compelled to rush off and cover terrible atrocities around the world. The relationship doesn’t go well. He cheats in her absence. 

I gave notes on the phone. My feeling about it was akin to how I felt about parts of Nathanial West’s “Miss Lonely Hearts” where this newspaper editor reads and responds to pathetic letters of human suffering sent in to the paper he works for.  

In Colvin’s script I kept thinking – why? Why does she do this? Why try to intervene in such hopeless situations? Why not stay at home and make the relationship work? I remember in Miss Lonely Hearts (which I read 30 years ago) the character had a girlfriend, and I kept hoping he’d get it together with her and settle down.  But he doesn’t and it ends sadly. 

I recall critiquing Colvin’s piece as a professional, explaining the need for some dramatic scene so that we know why she runs off to war, runs to danger, at the expense of her relationship. 

I may now be able to answer the question – but I need to backtrack. 

I hadn’t spoken to Cat Colvin for several years. Yesterday at 5 AM I woke early, and soon afterward Cat popped into my mind. I was thinking about whether she was still with that  guy from Boston.   

Sometime after 6AM I turned on CNN. Breaking news “journalist killed” flashes and a photo of a female with an eye patch appears on screen.  I knew instantly it was Cat’s sister because she had told me Marie lost an eye in some war.

I found yesterday’s coincidence odd and as the day wore on – for different reasons – disturbing.

I came to know Cat in 2000.  She, like her sister, had gone to Yale and was now working as a lawyer for IFC Films, part of Rainbow Media and Cablevision.  I had made an independent film “Some Fish Can Fly” that had been released briefly and was now being bought lock stock and barrel by Rainbow Media for not much money.  Cat was on the other side of the deal and we dealt pleasantly with each other concerning “film delivery items.”

In his film review, the Los Angeles Times critic, Kevin Thomas, noted that the filmmaker (me) appears to have made the film more than once:

     “The film, furthermore, is as ambitious in its structure, with Kevin vainly attempting to make a film drawn from his ambivalent romance while he has yet to come to terms with its ultimately impossible nature.”

 Pathetic but true. I actually had made the film twice -12 years apart -in the US and Ireland. I failed a little less the second time. Not enough money both times. Years of toil and poverty.

Why?

Days before the deal was to be closed with Rainbow, I pulled out. After all the SAG wage increases and such, my personal take would be around 10 thousand dollars for 3 years of work and I was giving away the copyright. I thought I might want to make the film again in a different way so I said no.  My partner was angry. I’m not sure what my wife thought.  I do know she doesn’t want me to make that film again.

In the summer of 2003, I had finished a cut of “Orwell Rolls In His Grave” a feature documentary I made about the Corporate News Media. I had begun filming in 2000, before 9/11.  I showed the film to Cat, who showed it to her boss at IFC.  There was interest and phrases like “we love it.”  IFC seemed to want to distribute the movie. Unlike my films about impossible love, this film dealt with our impossible media situation, and the havoc that such centralized media power does to our political system. The film itself was made during to the Florida Recount and the run up to the Iraq War.

Cat seemed sure a deal was going to happen.  Then there were delays, scheduling difficulties, all the while she continued to hear that “the boss loves it.”  This went on for a couple of months. Finally, another executive gave me a heads up. “The IFC is never going to buy this film, your movie goes against their business interests, the decision has come from upstairs”

I then call Cat: “But your boss just said he loves the film and wants to distribute it”

Cat responds simply: “He’s a good liar”

And so it went with “Orwell Rolls In His Grave” – a hit at festivals – untouchable for the major distributors, despite the interest and praise. It was like asking Turkeys to publicize Thanksgiving.  No film had ever discussed the media in such stark terms. Orwell Rolls… has become a ‘cult classic’- professors use it at Universities, libraries.  The film popular in places like Belgrade, Israel, Iran…

Why ever make such a film?

I have a new film “To Age or Not To Age” and a series on aging research and the implications.  I spent the last 5 years filming the molecular biologists, stem cell researchers and geneticists.

One of them – an Outlier – Aubrey De Grey, thinks there are people alive today who may live to a 1000 years or more. Aubrey looks medieval with a beard more than a foot long. He wants to get rid of aging and disease as a cause of death – a minor goal. Aubrey’s view nets him ridicule. I asked him why he got involved in aging research?  He responded; “I wanted to make a difference to the world”

I think his answer goes to why Marie Colvin’s character went to war.

It’s existential.  She was trying to intervene in the seemingly unstoppable human misery.  She wanted to do the impossible. Graft sense and meaning onto absurdity.

And this is the likely reason bloggers blog, and whistleblowers risk their careers – and why I make impossible films.

And why I woke up yesterday thinking about Cat Colvin.

We are all in this together, trying to push the rock up the mountain in our own ways.

 I read a response to a William Rivers Pitt blog last week that summed up Marie Colvin’s why.

It quoted the Talmud:

“Do not be daunted by the enormity of the world’s grief. Do justly, now. Love mercy, now. Walk humbly, now. You are not obligated to complete the work, but neither are you free to abandon it”.

an essay by Robert Kane Pappas

The political flap over the prominent and well-funded breast cancer advocacy group -Susan G. Komen for the Cure – cutting off financing for screenings at Planned Parenthood – was spoken about largely on a political Left/Right basis.  

In her New York Times essay on February 7th, Susan Love, M.D. poses a different and perhaps more basic question. Her view is that the real race in cancer is “finding its cause”; and she takes up the question of the efficacy of mammograms, laying out how according to British researchers, early detection saved one life for every 400 women between the ages of 50 and 70 who were screened regularly over a ten year period.  In terms of preventing deaths this is a tiny percentage. 

 Dr. Love explains that the underlying reason for this is that there turns out to be 5 or more types of breast cancer, some indolent, some virulent. The aggressive tumors have usually already spread by the time a mammogram finds them.  She concludes that early detection has its limits; the thing to do is to find the cause.

I have a few other ideas about this three legged chair of Politics, Medicine and Science. 

In the more than 5 years of investigation and filming molecular biologists and various researchers in connection with my forthcoming series on aging, “The New Fountains of Youth”, it has become clear that “cause” must be thought of in the plural, “causes.” Just as there is no one cause of aging, there is no one cause of cancer.

However in both aging and cancer research, the good news is that there are several nexus points (nexus genes), where scientists appear to be able to intervene. These genes control a cell’s – and hence the body’s – repair mechanisms. They inadvertently control aging, longevity, and speak directly to the question of the causes of cancer, and also, to the questions of why there are different types of tumors; why some women develop relatively harmless or curable versions of breast cancer, while others get the bad one.

 People with ‘good versions’ of these genes which control the cells’ repair mechanisms may get cancer, but they tend to get a type or degree of cancer that can be treated.

When I interviewed Nir Barzilai, M.D. Ph.D.,head of the Einstein Research Center on Aging,  for my series, he spoke of his study on several hundred centenarians and their children. Dr. Barzilai explained, in part, how they live that long. “Some of the centenarians look young, others, nothing will kill them, but they look old. A number of centenarians have never had a major illness, some of them smoked cigarettes for 90 years. Others get sick but they always get better.” They don’t have dementia or Alzheimer’s. 

The trick is that both groups of centenarians have good versions of certain nexus genes such as “telomerase.”  Their telomerase gene has certain mutations, which helps the gene do a good job of repairing the telomeres at the ends of each chromosome, which in turn keeps the cell intact longer when it divides. In fact, the centenarians have better versions of several key genes that regulate many cellular processes, including apoptosis, a process in which damaged cells commit suicide as opposed to becoming cancerous. This is one reason people with good versions of these genes survive cancer and live on for a long time.

To make a broad statement, the scientists have found that aging and disease are so closely related, that researchers now say that aging is the primary cause of all the major diseases. These genes control aging.  Control aging and you delay and ameliorate diseases. 

Nutrition and exercise have a strong impact on aging because they also influence these key genes. Environment and chronic stress impact aging genes. Some individuals have an inherited mutation, which increases the likelihood of developing this or that pathology. These ‘causes’ or “Risk Factors” influence the body’s repair mechanisms, causing it to age slower or more quickly.  These genes protect us from cancer.

Underneath all these factors, the primary cause of disease is aging. Tens of researchers have told me this. People who age more slowly either don’t get cancer or get manageable forms of it. This also applies to the other major diseases. They either don’t get them, or get milder versions of them.

Simple but true.

That’s the good news. Here’s the bad news.

The third leg of the chair of modern medicine and science is politics. In particular, GOP Politicians politicize common sense points of agreement with regard to medicine and science. Clearly, at a minimum, scientists will be able to keep us healthy and active longer. Economically,. prevention and delay of disease is obviously the answer. Every single scientist I spoke with said this.

The GOP will then talk about the budget deficit. Earth to the GOP – “Research Saves Money”, it’s infrastructure.

The business of politics and the politics of business influence both the scientific and medical chair legs. There is nothing good about creating wedge issues in areas where the entire population actually agrees. The mainstream media often discusses science and medicine in terms of conflict and sensationalism, or they play along with fools who try to make it a left/right thing – “ big government bad” –  hindering fruitful research in the name of balancing the budget (i.e., playing to voting groups).

Only 8 percent of research proposals are funded, which means 92% of them are not. The result is that scientists have to play it safer in order to get grants, which delays breakthroughs. To a man and woman, the researchers complained about this state of affairs.  And, other countries are in this game, they have scientists too. The political gamesmanship could export a blossoming industry.

What about the “private sector?”

The scientists say that large drug companies do little basic research work. Their primary concern is developing patentable drugs, having them approved by the FDA, and marketing them.

Moreover, major organizations like Susan G. Komen for the cure, groups which go after this or that disease, command major resources and funding, and tend to dominate what the media concentrates on and therefore what the public knows.

Several scientists argued that aging research goes after many diseases at once and should be more heavily funded than it is. The business and funding of science and medicine make this obvious solution much more difficult to achieve.

A couple of years ago Leonard Guarante Ph.D., head of the Paul Glenn Lab at MIT mused that he wasn’t sure what might happen if these discoveries produce a kind of silver bullet, ‘because various large organizations have a huge financial stake in the ‘status quo’ – from Big Pharma and the AMA, to large advocacy groups.

If we use our heads and avoid the easy labels and surface discussions, maybe we can get a fourth leg for that chair, design a better chair, make it cheaper, and create a new 21^st century industry that could easily rival the computer revolution. I believe there is progressive high ground to be staked out here.

To the scientists, the answer is simple.

But the 3 legged status quo chair commands the narrative and the lazy media’s attention. Herein lies the problem.

In honor of today being the bicentennial of Charles Dickens’ birth, let’s have this important scientific discussion without politics. 

The following is an extract from an article, The Genetics of Ageing, which was written by Cynthia Kenyon and originally appeared in Nature in March 2010.

“For many years, molecular biologists interested in regulatory mechanisms did not study ageing, as the tissue decline associated with ageing suggested a passive, entropic process of deterioration that occurred in a haphazard way. We know now, however, that the ageing process, like so many other biological processes, is subject to regulation by classical signalling pathways and transcription factors. Many of these pathways were first discovered in small, short-lived organisms such as yeast, worms and flies, but a remarkable fraction turn out to extend lifespan in mammals as well. In this article, I describe these pathways and their regulation by environmental and physiological signals. I also discuss unsolved mysteries in the field and, finally, the outlook for drugs that could slow ageing in humans.

Many people assume that extending lifespan by slowing ageing would mean certain death from, say, Alzheimer’s disease. Instead, we are finding that mutations that slow ageing also postpone age-related disease. This link raises the possibility of combating many diseases all at once by targeting ageing, their greatest risk factor. Fascinating as this topic is, age-related disease is not the focus of this article. Rather, its focus is ageing itself.”

The article goes on to discuss pathways that regulate ageing.

“We now know that the longevity response to dietary restriction is actively regulated by nutrient-sensing pathways involving the kinase target of rapamycin (TOR), AMP kinase, sirtuins and insulin/insulin-like growth factor (IGF-1) signalling. Unexpectedly, which nutrient sensor is most important in extending lifespan in response to dietary restriction depends on the way that dietary restriction is imposed. In C. elegans, for example, one nutrient sensor extends lifespan in response to life-long food limitation, another in response to every-other-day feeding and a third if dietary restriction begins in middle age.”

and notes

“Slowing ageing might seem like an overwhelming challenge, as the decline is so pervasive. So it is noteworthy that when we extend the lifespans of laboratory animals, we do not have to combat individually all the problems of age, such as the declining muscles, the wrinkled skin and the mutant mitochondria. Instead, we just tweak a regulatory gene, and the animal does the rest. In other words, animals have the latent potential to live much longer than they normally do.”

For the full text of the article, which is well worth reading, click here.

On the front page of the NY TIMES – August 19,2011 –Nicholas Wade reported on Dr. Rafael de Cabo’s newly published study on the positive effects of a resveratrol mimetic SRT-1720 on obese mice.  

To read the entire NY Times article by Nicholas Wade, click here.

I have followed this study, but I have also followed another one, linked and referred to in that article “the set back last year” – where in, George Vlasuk, Sirtris’ Chief Executive, announced that Sirtris had halted their resveratrol study. This story was also reported by Mr. Wade for the NY Times. 

What was striking, was that by discontinuing the study, an unspoken PR impression was created – namely, that resveratrol had failed or had been deemed to be ineffective. 

However, the interesting and significant thing here is that when you scratch the surface of the story, and see the facts as I have come to know them, the machinations behind the NY Times story become multi-fold – and curious. 

Last summer, I appeared with MIT’s Dr. Leonard Guarente on a number of radio programs and in interviews concerning his work in Sirtuin research and my film on the Science of Aging.  The subject of resveratrol came up a number of times.  Not only is Dr. Guarente a science advisor to Sirtris, the GlaxoSmithKline acquisition bringing forth the new SRT-1720 resveratrol mimetics, but he, at the time, was also an advisor to Dr. Sinclair and Dr. Westphal’s .org company, which in July 2010, was offering a Resveratrol formulation to the public.  The stated idea was to make this healthful compound available as a public service, in advance of any patentable mimetics, which carry the lag time of FDA approval.

 Soon afterward, GlaxSmithKline suspended resveratrol testing, and stopped Sinclair, Westphal, et. al., from continuing to sell resveratrol through their .org company. And soon after, the damaging article appeared. 

In that article referenced in Wade’s August 19^th piece, Sinclair actually disagreed with GlaxoSmithKline’s decisions about resveratrol and said so.  

Now, the positive results of a new patentable compound is reported upon. There is no direct mention of what happened with resveratrol. Sinclair is involved with the new study, everyone is upbeat. 

I have a certain perspective on the goings on behind the scenes. And this in turn highlights how the media reports on a subject, and how that methodology can lend itself to misinformation. 

For instance, in Wade’s article, he quotes Brian Kennedy, CEO of the Buck Institute, who strikes a cautionary tone at the end. It just so that I filmed an interview with Dr. Kennedy, in which he discussed getting calls from reporters like Mr. Wade, looking for opposing views.  The video gives insight into the media’s methodology. The clip can be viewed below.

The real story is the trajectory of the research.  Scientists will continue to attempt to disprove one another, that is the nature of the scientific process.  It is the pace of their advances that is striking.

On Sunday, July 31st, filmmaker Robert Kane Pappas was the featured
on The Staying Young Radio Show.
Robert was interviewed by Judy Gaman, along with Dr. Walter Gaman
and Dr. Mark Anderson on new breakthroughs in the science of aging.

The audio from the program The Science of Aging with Robert K. Pappas is attached here commercial-free [...]

One content note in the program for the David Sinclair/Bruce Yanker hosted aging Symposium certainly catches your attention. It’s the blurb at the bottom of Dr. Jonathan L. Tilly’s page outlining his presentation.

“Rewinding the Female Biological Clock for Fertility Reasons: An End to Menopause as Well?”

To me, this exemplifies the stunning hints of the deep human implications that aging research holds. How will society evolve when women are no longer driven by concerns about their biological clocks?

Behind these findings lies a recurring idea:

IT’S ALL ABOUT SIGNALING

Over the past several years, a number of scientists have recounted an experiment wherein researchers combined the bloodstreams of a young and an old mouse. Suddenly, the old mouse’s muscle tissues began to repair like a young mouse’s, that is, to act younger.

What this means is that the old cells are driven by their environment and retain the ability to become young again.  In the case of Tilly’s work, aged ovaries placed in a young environment became viable again,

 “based on his [Tilly] discovery of a population of stem cells in the ovaries of adult mice that are capable of generating new eggs”… “ovarian failure can be reversed through germline (egg) stem cell-based technologies.  He [Tilly] has also discovered a similar population of egg stem cells exists in humans.”

Another recurring motif in the scientific presentations could be phrased like this:  “We expected to see X but we were wrong.”  As I understand it, the reasons for the unexpected or contradictory results have to do with “Occam’s Razor.”  By this I mean that the results appear at first to be counter-intuitive.  But, as the scientists bore deeper into the mechanics of what is going on, the initial contradiction doesn’t hold.  Dr. Lenny Guarente explained this to me four years ago with glee. Scientists are trained to explore a question while making the fewest assumptions, which leads them to follow what appear to be logically predictive paths.  The point is, “Occam’s razor is not always correct.” This continual “reassessment” of what we assume to be true is the hallmark of aging research.

TO AGE OR NOT TO AGE will air on LINKTV this month beginning on Monday, June 20th at 11 am Pacific Time/2 pm Eastern Time.  

The airdates are as follows:

Monday, June 20th, 11:00 am PT/2:00 pm ET

Wednesday, June 22nd, 11:00 pm PT/2:00 am ET

Saturday, June 25th, 2:00 am PT/5:00 am ET

Saturday, June 25th,  3:00 pm PT/6:00 pm ET

LINKTV can been seen on DIRECTV Channel 375 and DISH Network Channel 9410.  For more information click here.