Dissecting a mouse

Over the course of almost fours years, while making TO AGE OR NOT TO AGE, director, Robert Kane Pappas, visited Dr. Lenny Guarente’s lab at MIT several times.  During that time, he met and filmed many of the post docs working in Dr. Guarante’s lab.  One such researcher was Gizem Domez, who was recently featured in a New York Times article for her discovery of a potentially promising way to treat Alzheimers disease.

Click here to read the article by Nicholas Wade that appeared in the NY times on July 24, 2010.

Below are Pappas’ reflections on meeting Gizem, at the time, a new recruit in Dr. Guarente’s lab:

“I met Gizem Donmez the second time I visited Dr. Lenny Guarente’s Lab at MIT.  The young scientists (recent Ph.D’s known as post docs) eat their “to go” lunches around a 12 foot square table in a conference room, with a coffee maker, refrigerator against one wall, and a blackboard decorated with random molecular notations stretching the length of the opposite one.

I was filming their comings and goings. Gizem had only been at the lab for a couple of months, a lovely looking young woman with dark hair. 

Though educated in Turkey, she spoke better English than I do.  Her mother wanted her to be a doctor, an MD.  “Why didn’t you become a doctor, the pay is better”  she mimicked.  Young post docs are much more upfront than older researchers; Sergie from Ukraine would throw out some barbed comment.

Gizem was studying Alzheimers in mice.  We were talking about their humane treatment – I had not gotten the lab to allow me to film where the mice are kept, such was the care taken so they would not be accidentally contaminated.  In the midst of this Gizem blurts out  “I mean …I kill them”  -  explaining how they are bred and altered to get Alzheimers.  Young Post Docs are not politically correct. Later, on another day, there she was, in lab coat and mask in a partially enclosed germ free area, precisely dissecting a mouse. tiny probes connected to it’s body. You see her in the film doing this.

A couple of months ago, I was up talking again to Lenny about his newest research and ran into Gizem.  Her hair in new style — a slight wave — the same sweet expression.  She had now been at MIT for 3 years and her work with mice had literally just been published that day in Cell.

I was just finishing my film. I told her she made the cut.  Later, Lenny called her “one of [his] superstars”.”

Robert Kane Pappas

July 29, 2010

To Age or Not to Age: Intriguing Research Featured in New Film

By Michelle Seitzer

[The following article was originally posted on Seniors For Living on July 27, 2010.  Click here for the original article.]

People in New York City were treated to an interesting new film, To Age or Not to Age, this July at the Village East Cinema. Here’s the premise… Four leading scientists – Dr. Cynthia Kenyon, Dr. David Sinclair, Dr. Leonard Guarente, and Dr. Aubrey de Grey – are featured along with their groundbreaking research which begs the question that gives the film its title: To Age or Not to Age.

According to the researchers, it may not be far-fetched to imagine a world where aging is postponed, perhaps indefinitely, and aging-related diseases are eliminated. One scientist postures that we can eliminate/reverse the aging process itself.

Check out this thought-provoking quote from Dr. Thomas Kirkwood, which captures the essence of the film’s rather controversial premise:

“A lot of people think we’re biologically programmed to die, but the truth is that we’re biologically programmed for survival. There is no mechanism inside us that turns on to kill us when a certain period of time has elapsed.”

Many of us know or have heard of people who are aging very gracefully: doctors that we’ve profiled in previous blog posts who still go to work after turning 100, the members of the Young@Heart chorus who tour the country and boast members near/at the age of 100 <http://www.youngatheartchorus.com/about.php> , Nelson Mandela who started a new venture (check out my latest post on “The Elders”) to celebrate his 89th birthday, your next door neighbor who just graduated college at age 85 or the family member who still goes to the gym at age 92 – the list goes on. So is the idea of the film really that far off?  What keeps these people moving forward, despite their advanced years?

There are certainly many implications (moral, economic, etc.) for reversing/eradicating the aging process. The film explores these potential repercussions and opens up an opportunity for dialogue on this fascinating subject.

Look for a future blog post on my interview with one of the film’s scientists…and in the meantime, share your thoughts on the film’s premise here. 

Aging is Old Hat

By Gerit Quealy 

[The following is an except from an article originally posted on Huffington Post on July 26, 2010] 

Dr. Leonard Guarente

Summer movies usually mean blockbusters. But the new film TO AGE OR NOT TO AGE belongs more in the realm of myth busters. 

Sidestepping long lines for  Inception, I traded in Leonardo DiCaprio for Dr. Leonard Guarente of the Glenn Laboratory for the Science of Aging at MIT, explaining how research is bringing dreams of a fountain of youth closer to reality. 

Sexy stuff? Well, yes. Wriggling worms and a protracted reproductive cycle aside, I’ve found scientists more and more sexy (with the exception of my high school chemistry teacher). When what emanates from the gleaming bald pate of Dr. Guarente illuminates the hard science behind staying young, you can feel your pulse quicken. 

The cast includes a phalanx of scientists, cells, mutant genes, a cameo by a 405-year-old clam that was born the year Hamlet was first performed on the public stage, and a parrot. The plot? “A profound mystery” says Gordon Lithgow Ph.D. of the Buck Institute, but also part science fiction, part reality show. 

Not to mention whodunit. We’re essentially talking about the death of aging. And how exactly the scientists are going to do it. “It’s huge,” agrees writer/director Robert Kane Pappas in a brief conversation. “I had to do a sort of Cliff’s Notes to touch on everything.” 

And he does, but the film unfolds gently, so it’s easy to miss how packed it is with information. Research on cancer cells that don’t die, longer lives for monkeys through caloric restriction, longer lives for mice through the consumption of resveratrol, a compound from grape skin that’s been touted as a sort of Fountain of Youth by the mainstream press — are all spotlighted. (Pappas admits he is taking resveratrol. As are many of the other scientists.) 

“It’s the best possible time to be alive, when almost everything you thought you knew is wrong,” says a character in Tom Stoppard’s play Arcadia. 

For the full article click here. 

Nobuhiro Hosoki interviewed Robert Kane Pappas in New York City on July 15th. 

[The following is an excerpt from the interview which was originally posted on hosokinema.com]

To Age or Not To Age

Coverage by Nobuhiro Hosoki

Story : Is it possible to live forever? In this documentary, filmmaker Robert Kane Pappas explores the possibility of staving off old age and, as a result, the onset of disease. Some scientists claim the genes that control aging can be altered to give us more time on Earth – quality time in which we could be both happy and healthy. But what would be the moral implications of such experiments, and who would benefit from these potential medical breakthroughs?

 Interview Director Robert Kane Pappas

 Q: I try to gather the story in Japan, and because there’s a lot of work that I’m not familiar with, so in order to get the story I started looking up those medications that were prescribed, but there’s not much information in Japan to put a story together. It might take some time to get to another country but it’s really interesting. How did you decide to get into it?

 (Robert Kane Pappas): I am a film director; I’m not a scientist. The picture before this, my last picture, I made a movie on the structure and methodology of the news media and it’s affect on politics. My last couple of pictures, I pick a subject that interests me, something I see, and then if it passes the smell test I spend those couple of years making that picture. So one day I read the front page story of the “New York Times” science section; it was about calorie restriction and its effect on the lifespan of monkeys.

 There are scientists at Harvard and MIT who are looking at the genes behind this calorie restriction and it’s affect on health and lifespan. Two days later they amplified on the story, the “Times” again, the front page of the main section said there was something in red wine they had found that seemed to influence these genes. But in the story the lead scientist, David Sinclair, the lead Harvard scientist, admitted that he’s taking resveratol and that half his lab was taking it, his parents, his wife. And these scientists are not crazy people; they’re very conservative by training and by temperament.

 So I said this is very unusual, this is very strange for them to be saying I’m not only testing it on animals and humans, I’m going to start taking it. This to me said something a little odd was up here. So then I started researching it, I went and tried to interview the scientists, I called Dr. Guarente’s office and I said I’m a film director, you can look me up, could I interview you? He said “Well, read my book first.” So I had to kind of prove myself a little, and then I started interviewing him, and then I interviewed some of the people in his lab, and then I said is there someone else I should speak to? And then he showed me someone else and then I called someone else, and that person said well go talk to this person, and three years later I made a movie on these scientists and their research.

 Q: You probably won’t be able to answer this question, but how about the government that’s funding this research in universities or in colleges right now?

 (Robert Kane Papas): Lenny(Doctor. Leonard Guarente) told me that even at his high level only seven or eight percent of the grant proposals are funded. That means 92 or 93 percent aren’t. I think that there are probably a lot of disease doctors who want funding for my disease, or this doctor is studying this disease, whereas, these guys are going at aging, which used to be something of fiction; Ponce de Leon or they myths in the history. SO I think it used to not have the credibility. But these are the top scientists of the world that are working on it right now. The Nobel for biology this year was in this field; Elizabeth Blackburn. She discovered Telomeres, or has been working with Telomeres.

 Q: I’ve been looking up Telomeres but it’s not in the dictionary. 

(Robert Kane Papas) : It’s not in the dictionary. A lot of this is really cutting edge stuff. And how the government funds I think is really going to be a big issue.

 Q: I guess it’s because of the aging process these diseases actually progress. Like you guys said, I think it really tied into it. So once they convince those elements to the government, I’m pretty sure that in the future, maybe five or 10 years, they might probably get more funding.

(Robert Kane Papas): And it’s possible other countries will be going ahead. At MIT and Harvard that brings the best in the world. By the way, Lenny Guarente’s lab, of the 17 scientists in his lab, which is probably the most renounced lab, I think 12 are from foreign countries. The best in the world come there. But then from there how does it funnel out? Different countries may go ahead; if they fund the research better who knows? I don’t know.

Q: Maybe also the healthcare system might be involved. Compared to the United States, the health care systems in other countries have better delivery.

 (Robert Kane Papas): So how it’s going to develop is up in the air. The bureaucracies have the tendency to status-quo. I think these drugs could be, we could be talking hundreds of billions of dollars, so whenever there’s that much money around trouble can ensue. I think the basic science, once you put together the fact that evolution doesn’t particularly care about lifespan, and all their techniques to go so much faster in their research, I think putting those two together made me as a filmmaker think that we could be on the verge of something completely different for humanity.

And that is really a big deal because they’re not doing experiments; they’re designing experiments now to reverse aging. This is not going to stop. They are at the beginning of this, they are not at the end of this. This is the first act and it’s really a big deal. This is some very strange stuff going on here around the world. Remember that there used to be three or four labs 20 years ago; there are 400 now, at least.

 Q: When you look at the people in their 40s or 50s, 50 years ago it didn’t look like that. But right now a 40 or 50 years old looks like they’re in their 30s or something. It’s so much different from a few decades ago.

 (Robert Kane Papas): This could be really, really basic. This could be the biggest thing that’s ever happened to humanity, actually.

 Q: Yeah it could be. Talk about the side effects that they might have if they can actually stop aging or live longer.

 (Robert Kane Papas): I don’t think we know. I think that it will be slow. First of all, if you can keep people healthy you can start to reallocate resources. But I think that if you live longer, especially now that they’re looking at when you delay aging you also delay the deterioration mentally. I would say that you are not thinking the way you thought when you were 10, that you developed intellectually.

 If your mental process is intact you could become much brighter. It’s quite possible that you would think completely differently if you lived a lot longer. Conceptually, consciously; your sense of time would probably be radically different, because when you’re five years old or six years old a month is forever. Many things will change; I don’t think we know what they will do. But I think that when people say you can’t change human nature, or history always repeats itself, I think that a lot of that is based on how long we live.

 I think you would think of the environment a lot differently if you were going to be around. And George Bernard Shaw, who I quote in the movie, had this thing called “Back to Methuselah,” this play, and he spelt that if humans live to 300 years we would change radically, our politics would change radically, that we would be thinking a little bit more long term, we wouldn’t be like “I have mine, screw everybody else.”

 So you could see there would be possible changes in human nature. It’s funny that there’s another Great Depression 80 years after the last one. It’s like the historical memory; no one was around and they’re doing the same thing again. It makes everyone think like can we ever not make the same mistakes? It could be that it’s tied to our age; how long people live.

 Q: That could be mentally change how you deal with society.

 (Robert Kane Papas): Yeah, or your career. If you live longer you could have more than one career. It wouldn’t be that okay you’ve made your decision that’s it.

 Q: And the retirement age might be in the 80s or 70s or whatever.

 (Robert Kane Papas): That could change. So I think all that is up for grabs. He’s very conservative, Lenny. He’s a very conservative scientist.

For the full interview with Robert Kane Pappas click here.

To Age or Not to Age

By Brian Whisenaut

[This amusing review was originally posted on Awards Wiz on July 16, 2010.]

“To Age or Not to Age” is a new documentary opening in NYC on July 16th, directed by filmmaker, and everyman, Robert Kane Pappas.  The film questions whether or not aging and death are quite the absolutes we have always imagined.   Even before the film starts I begin to think about the consequences of longer life.  Overpopulation…leading to what?  Limits on children?  Habitation of other planets?  Is this something that should even be considered?  And, won’t people be too scared to talk about it?  So much is put into preventing death, is it blasphemous of me to think living longer is a bad idea?

Pappas begins his narration by telling us how he “discovers” a film subject.  In this case, he read an article in the Science section of The New York Times about how calorie restriction lead to a healthier and longer life in mice.  When Pappas becomes interested in a subject, he decides to learn as much as he can about it until he is an expert.  He is starting from scratch here, which gives me great hope that I will be able to follow along with this scientific mumbo jumbo (and to be frank…not get bored.).  Basically scientists are beginning to determine ways to make the genes in humans react similarly as they do with calorie restriction, but without us starving in the process.  As more progress is made, it appears we may be able to live 10, 20 years longer…sooner or later.

As the film began to move along, introducing us to more scientists (including the very interesting Aubrey de Grey, a sort of rogue scientist who believes we could live for 1000s, possibly millions of years and Rev. Nicanor Pier Giorgio Austriaco, who goes from scientists, to priest, to scientist/priest, both of which give very important perspectives to the story.)  I begin to realize that I am completely engrossed in what is being discussed.

Click here for entire review.

To Age or Not to Age

By Shannon Gramas

[Originally posted on spectrumculture.com (where snobbery and trash collide) on July 19, 2010.  Click here for original article]

Dr. Aubrey de Grey and Robert Kane Pappas

In the series of Future History stories written by the science fiction author Robert Heinlein, mankind has developed the technological capability to arbitrarily extend the human lifespan. Repeated applications of the so-called “rejuvenation” process can allow a person to enjoy thousands upon thousands of years of healthful, youthful existence. Reading these books as a teenager, I thought the idea sounded absolutely wonderful. Who wouldn’t want to live forever? Looking at the question now though, I’m not so sure. Call it maturity, call it “wisdom,” but as I’ve grown older I’ve come to the realization that death is the only thing that gives life meaning. To eradicate death would be a grave error (pardon the pun). Without the aging process, human beings would never mature. Time etches wisdom in the body itself, and to take that process away would suffer us to the unimaginable fate of being teenagers forever.

Luckily this idea has always stayed within the realm of science fiction. That is until now, if you are to believe Robert Kane Pappas. In his new documentary, To Age or Not to Age, Pappas interviews several scientists at the forefront of the life-extension revolution. While most are typically conservative in their predictions, at least one of those interviewed believes that it is well within our capacity as a species to completely eliminate aging and disease as a cause of death. This is Dr. Aubrey de Grey, an ebullient and extravagantly-bearded Brit whose radical predictions cause a degree of consternation amongst his more soberly-minded fellows.

For example, de Grey believes that the first person to live to see 1000 years will be only 10 years younger than the first person to reach 150. In other words, in only a decade the technology will have advanced to the point where a lifespan of 150 will seem like an early death. And both of these people are potentially alive today. He figures that with constant, incremental advances in technology, the first procedure to modestly extend life spans will soon be supplanted by a more robust procedure that can then be re-applied before the original, less efficient application has worn off. On and on we go in an ever-increasing exponential explosion of technological advancement that will end in humankind becoming functionally immortal.

Let’s suppose you do an experiment on the effects of an extremely low calorie diet on mice and find that compared to a control group, the calorically restricted mice have significantly extended life spans. Upwards of 20-40 percent longer, in fact. And let’s further suppose that with a little digging you discover that a certain gene, dubbed “SIRT1″ is responsible for this effect. It is what is known as a “regulator gene,” and increasing its activity in a yeast sample will also slow the aging process in that species. This is what Dr. Leonard Guarente discovered in the late ’90s. One of his students, Dr. David Sinclair, made the further discovery that a certain molecule found in the skin of grapes, resveratrol, can activate this and other similar genes, mimicking the effects of caloric restriction. Soon a field of study is born, scientists making similar discoveries left and right.

Intrigued by these findings, Pappas decided to make a movie about the phenomenon of artificially-induced life extension. Over a three year period he interviewed Guarente, Sinclair and other leading scientists in the field and came away with this thoughtful, information-dense documentary that left me with a feeling of awe at the many ingenuities of the human mind, when it wasn’t totally scaring the pants off me.

Interspersed between the fascinating interviews are a series of vignettes wherein Pappas attempts to tackle some of the wider, philosophical implications of this research. He set up a number of dinner parties where groups of similarly-aged people (“30-somethings,” “50-somethings,” etc.) discuss the issue of life-extension amongst themselves. I was gratified to hear that most were not in favor of the prospect, or were at least greatly skeptical of the supposed benefits. Many were quick to point out the inevitable social inequities that would arise when such life-extending procedures became available. Only the rich, white, Western world would reap the benefits, they argue, thereby exacerbating the already sizable gaps between the “haves” and the “have-nots.” And what about overpopulation? What about the environment? Our planet is already taxed to the utmost in trying to support six billion people who will live a century, at the most. What will happen when that number doubles? Trebles? Quintuples? The mind staggers.

I wish that Pappas had gone further in this direction. Much of the documentary comes off as a commercial of sorts for the technology, and for one company in particular, Sirtris. Founded by Dr. Sinclair, the company was eventually absorbed by pharmaceutical giant Glasko Smith Klein, adding a much-needed sense of legitimacy to the endeavor. The only thing standing in the way of further research was money, and once GSK finds a way to monetize life-extension, the sky’s the limit.

To Age or Not to Age makes a persuasive argument that the era of greatly increased life spans is soon to be upon us. It has left the pages of science fiction novels and become reality. The only question is whether that reality will be a fulfillment of all our fondest dreams or of our most hidden nightmares.

Should We Still Age?

By Gerit Quealy

[Posted on stylegoesstong.com on July 16, 2010]

Summer movies usually mean blockbusters. But the new film TO AGE OR NOT TO AGE belongs more in the realm of myth busters.

The documentary, opening today in New York and soon to a little indie movie house near you (or add it to your NetFlix queue), explores the science behind aging the and the breakthroughs that are happening, faster and faster, that lead some to believe that our life spans can be significantly extended.

So while everyone else is standing in line to see Inception, I traded in Leonardo DiCaprio for Dr. Leonard Guarente talking about the accidental discovery of the yeast gene.

I don’t know about you, but over the years I’ve found scientists more and more sexy (which would stun my high school chemistry teacher, whom I still don’t find sexy and never will). You can keep your Tom Cruises and Johnny Depps. Give me the gleaming bald pate of Dr. Guarente — like a light bulb in a dark room  –  illuminating unexpected possibilities.

That isn’t to say that I want to live to 1000, or even 100, and the film explores the  myriad facets that delaying aging and living longer, much longer, entails. “It’s huge,” witer/director Robert Kane Pappas admits to me during our brief conversation. “I had to do a sort of Cliff’s Notes to touch on everything.”

And he does; it’s a deceptively simple film that encompasses the health care system, big pharma, disease prevention, financial impact, and religion/existential questions — to wit, one of the scientists who made a breakthrough discovery has become a priest.

To read the entire article (and it’s well worth it), click here

On Thursday, July 15th, Robert Kane Pappas and Dr. Leonard Guarente sat down with Leonard Lopate at WNYC to discuss TO AGE OR NOT TO AGE and the science of aging explored in the film.

Click here to listen on line.

“TO AGE OR NOT TO AGE” Claims Drugs Will Soon Extend Life, Slow Aging, Re-Grow Teeth

By Jill Schuck Taylor

Posted July 16, 2010 on Stylist.com

Buried amid this summer’s cinematic offerings of vampires, explosions and animated characters, you’ll also find a thought-provoking documentary called “To Age or Not to Age,” opening tonight, Friday, July 16^th.

Filmmaker Robert Kane Pappas collected an impressive bunch of scientists to look into whether or not it’s possible to delay that whole getting-old thing by altering certain genes that control the aging process.

For the entire article click here 

TO AGE OR NOT TO AGE opened last night at the Village East Cinema on 12^th Street and 2^nd Avenue.  Director, Robert Kane Pappas, led a Q&A following the 5:30 pm and 7:45 pm shows.

The audience loved the film and asked a wide range of questions until they were ushered out by the Village East staffers.

A couple of curious events:  outside in the theater hall after the Q&A ended, the director  and producer were approached by a quiet mannered audience member, who volunteered

 “ I must tell you, I read the Times review, and just saw the film, and that review had nothing to do with this film. Very strange”.

A second associate entered the bathroom as two patrons were conversing: one said

“This movie’s great – thank God we didn’t listen to that stupid New York Times review”.

The moral of the story, don’t be put off by a malevolent review.  Join Robert again tonight after the 5:30 pm and 7:45 pm show and see for yourself.