Time: Immortality & Ageing - Michio Kaku

TIME | 2. LIFETIME Friday 20 October 2006 7pm-8pm TBC

Why is our time limited? And does it have to be? Could our age-old dream of immortality ever be possible? In episode two, Michio Kaku explores these questions and meets some of the key people involved in the cutting-edge research into ageing. He travels to the amazing Methuselah tree, which is almost 5000 years old and still producing new pine cones. He discovers that time does get faster as you get older and, under hypnosis, he goes in search of his lost time, stored as memories. But it only proves that lost time is really gone forever.

We are incredible machines for living - but if we're programmed to live, are we also programmed to die? As we grow, our cells divide into a complex colony of three trillion individual cells in our bodies. Sir Paul Nurse has spent a lifetime studying cells to search for the most basic process of life - the secret of cell division. We discover that cells seem to be potentially immortal. They continue to divide again and again perfectly. Even our own bodies are replaced through our lives - most of our cells are replaced in a roughly seven-year cycle. Yet we know that we age and that time wreaks changes on our bodies.

This episode reveals the biological changes in our cells that make our skin wrinkle and our bones become brittle. This new understanding is beginning to reveal the process of time in our bodies and, through this, scientists are now looking at ways of slowing or even stopping time. Scientists in California are studying sea urchins for clues as they not only live longer than ever thought before but they appear to show no sign of ageing. Genetic manipulation is extending the lives of mice. And a British scientist is now suggesting that the pace of advance is so fast that the first immortals are already living today; that before our children have reached the end of their natural lives, the technology to stop and even reverse ageing will exist. But what will that mean for our essential humanity?


WATCH VIDEO CLIPS
An experiment which proves time does get faster as you get older
How genetic research into ageing has produced extraordinary possibilities for extending life

Ph.D. admission with a 2.2 and a Masters degree

Admission to a Ph.D. programme within the UK generally requires the prospective student to have completed an undergraduate Degree, either with First Class Honours or Upper Second Class Honours (known as a 2.1). A Masters degree is also highly desirable, which is seen to increase the primary degree by one classification, thus making it possible to gain admission with a Lower Second Class Honours Bachelor's Degree (known as a 2.2) and a Masters degree (e.g. MSc, MRes, MPhil).

A 2.2 & a Masters. That's me. So maybe one day I'll do a Ph.D!?

International Association of Biomedical Gerontology, 11th Congress - Meeting Report

Biomedical gerontology is a profoundly distinct idea—unlike clinical gerontology, whose focus is on the use of existing technology to improve the health of the elderly, and also unlike biogerontology, which concentrates on understanding aging as opposed to doing anything about it. Rather, biomedical gerontology is about developing new techniques to combat aging more effectively than we can at present.

Demetrius (USA) presented his reasons for predicting that humans will not derive a longevity benefit from calorie restriction, while Hipkiss (UK) proposed a novel mechanism whereby caloric restriction might work via a reduction not in oxidative phosphorylation but in its ostensibly more harmless precursor, glycolysis, on the basis that glycolysis generates glycationinducing byproducts. He also drew attention to the possible beneficial effects of carnosine on this process.

How far, then, are we from serious life extension in mammals and eventually in humans— and in particular, how far are we from life extension that merits the term “biomedical” by virtue of being applicable to those who are already on the slippery aging slope? IABG11’s organizers are well known to be skeptical of my views of how, how much, and how soon aging can be postponed. I was able to draw attention to the just-announced SENS Challenge.

Mitochondrial DNA Mutations, Apoptosis, and the Misfolded Protein Response

REJUVENATION RESEARCH Volume 8, Number 4, 2005. JUSTIN L. MOTT,* DEKUI ZHANG,* and HANS PETER ZASSENHAUS

ABSTRACT
Studies of mice with accumulated mtDNA (Mitochondrial DNA) mutations in the heart lead us to propose that apoptotic signaling and cell death is central to the pathogenesis of mtDNA mutations in aging. It is the cellular response to that apoptotic signaling and the organ’s compensatory response to a loss of cells that specify the phenotype of an accumulation of mtDNA mutations. In the heart, cardiomyocytes induce a vigorous anti-apoptotic, pro-survival response to counteract mitochondrial apoptotic signaling. The heart up-regulates contractility of remaining myocytes in order to maintain cardiac output. We hypothesize that mutant mitochondrial proteins originate apoptotic signaling by interacting with proteins already in place in the mitochondrial outer membrane that regulate apoptosis, for example the pro-apoptotic protein Bak. Since it is unlikely that all mutant mitochondrial proteins have the necessary structure and localization within the inner membrane to activate Bak appropriately, only a small fraction of an age-associated burden of mtDNA mutations may be pathogenic. In this model, reactive oxygen species generated by mitochondrial respiration drive the formation of mtDNA mutations, but are not the primary mechanism for their pathogenicity.

Summary
MITOCHONDRIAL DNA (mtDNA) mutations accumulate with age and disease. These sporadic mutations randomly affect the mitochondrial genome, and thus a mutation at any particular nucleotide position is rare. Even with advanced age, the frequency of mutations generally does not exceed 1% in otherwise normal individuals. Thus, for these mutations to cause disease or senescence, the cell needs to be very sensitive to mtDNA mutations. Recent evidence suggests that the burden of point mutations in mtDNA may be higher than previously thought, so that estimates extrapolate to an average of three point mutations per genome in the aged brain. Still, given the random distribution of those mutations and the multiple copies of mtDNA per mitochondrion, their effect on respiratory function would be expected to be slight.

Despite their low frequency, mtDNA mutations are still more common than nuclear DNA mutations. Because of the compact nature of the mitochondrial genome, these mutations are also more likely to affect a coding region. Due to heterogeneity, the mutation level may be higher in a given cell than the overall average of the tissue. At the next level of compartmentalization, the mitochondrion itself will have an even higher proportion of mutant genomes. Consider a cell that has only a single mutation on a background of maybe 1000 wildtype mitochondrial genomes. The tissue mutation level may be undetectable, the cellular mutation level would be 1/1000 genomes. But the level of the mutation in the affected mitochondrion would be 10–50% (given two to 10 genomes in this prototypical mitochondrion). If mtDNA mutations contribute to disease, the signaling mechanism must sense the high proportion of mutation within a mitochondrion, not the low proportion of a cell or tissue. The central tenet of the mitochondrial theory for aging is that those signals are reactive oxygen species (ROS), natural byproducts of mitochondrial respiration. The ensuing oxidative damage mutates mtDNA, leading in turn to even more ROS because of malfunctioning respiratory enzyme complexes, all of which, with the exception of Complex II, contain protein subunits encoded within mtDNA. The “vicious cycle” of ever increasing frequencies of mtDNA mutations and oxidative damage ultimately causes cellular senescence, in part because of accruing oxidative damage and in part because of declining mitochondrial oxidative phosphorylation. We argue here that apoptotic signaling is the primary pathogenic mechanism of mtDNA mutations in aging. It is now well established that mitochondria play a central role in amplifying cellular apoptotic signals within the intrinsic pathway for apoptosis. It is within mitochondrial membranes where interactions take place among pro- and anti-apoptotic proteins such as Bak, Bax, and Bcl2 to regulate outer membrane permeabilization and cytochrome c release, unleashing the caspase cascade culminating in apoptosis. We propose that mutant mitochondrially encoded proteins tap into that machinery already in place so as to originate apoptotic signals. At any one moment, most cells sensing those signals suppress execution of apoptosis by up-regulation of antiapoptotic proteins. Nevertheless, some cells succumb. Finally, we will present a hypothesis bearing on the molecular mechanism(s) for how mutant proteins might originate apoptotic signaling—a process we view as a mitochondrial misfolded protein response.

Tony Blair's 'light of science' vision

Listen to the 41 minute speech by Tony Blair on Science at The Royal Society or a 2 minute taster.

In 1963, a previous Labour prime minister, Harold Wilson, called for a new Britain to be "forged in the white heat of this [technological] revolution".

Nearly half a century on, Tony Blair is to call for more of the same. He told me that now, more than ever, our economic future is through "the brilliant light of science".

Unfinished business

This is a prime minister with a mission.

I want to enthuse our young people particularly with the prospect of working in science Tony Blair PM's call for young scientists

"It's not just about being a boffin in a laboratory - it's actually about practical application and transforming lives, tackling the world's problems and doing so in a very practical way."

Specialist colleges

Mr Blair has also presided over a time where the numbers of young people studying physics and chemistry have dwindled by a fifth. And a quarter of schools have no qualified physics teachers.

We've got to invest in science far more as a country Tony Blair

This is a deficiency he acknowledges but says he's trying to put it right.

"We've got to invest in science far more as a country.

"The government is tripling investment in science - to recruit better science teachers - which is why we're offering all sorts of incentives for that to happen.

"We've got specialist science and technology colleges which we are creating."

However, investment is well short of the target set by the European Union's aim of being the "most competitive, dynamic knowledge-based economy in the world".

That's a statement from the EU's Lisbon Strategy which aims to match the US's research funding of about 3% of GDP by 2010.

Currently, Britain's is just over 1% but it is set to increase to 2.5% by 2015. Other EU member nations are moving even more slowly.

We should not get into the position of being anti-science as a country because how science is applied and how it's used is down to human beings to make decisions about Tony Blair

The man who helped re-brand the Labour party believes that it's partly an image problem. It's a problem, he says, that's partly caused by the "antis" - the anti-GM groups, anti-vivisectionists and the anti-nuclear lobby that create a negative image of science.

"We should not get into the position of being anti-science as a country because how science is applied and how it's used is down to human beings to make decisions about.

"But for us as a country, where the future is as a knowledge economy, science will, in my judgement, today and for future generations, be as important as economic stability was when we were handling the problems in the 1970s and 1980s and 1990s."

But that's what prime ministers have been saying for decades. Most researchers are delighted at what the government has done for them.

However, with huge research investment by India and China, senior researchers say that now is not the time to rest on laurels.

Exhortation and evangelism by the prime minister is welcomed - but on its own it, they say, it won't be enough.

'Irrational' science debated

Tony Blair has outlined what he believes is the damage that "irrational public debate" can have on our understanding of science.

Steve Jones, professor of genetics at University College London and Dr Doug Parr, Greenpeace's chief scientific adviser debate the issues.

Tony Blair on Science

Note: This article contains the entire interview with Tony Blair. Edited highlights of this interview were published in the print edition of New Scientist - that shorter version is available here.

Audio: Download our exclusive podcast of the entire interview here (11MB, mp3 format).

During the 10 years he has been in office, British prime minister Tony Blair has presided over some dramatic developments in science and the way it has impacted on society in the UK, from advances in cloning to the closening relationship between science and business.

He’s also been in power during two hugely controversial incidents: the refusal of people in Europe to accept GM crops, and the refusal of British parents to have their children vaccinated with the measles, mumps and rubella vaccine.

On the eve of an important speech Blair is making on the future of UK science, he talked to Jeremy Webb about why he thinks science is so important to society, where he think things went wrong with GM and MMR, and how such issues would be resolved far more easily if scientists engaged more in the public debate.

How good were you at science at school?

I’m very open about this. I was very poor at science at school. I’ve become a lot more interested in it in later life, and I’ve also started to regret that when I was younger I didn’t engage with it more fully and learn more.

Why didn’t you?

I found the basic concepts difficult to understand. It’s only in later life I’ve started to think about it more and look at it more. It’s also only as a political leader that I’ve really taken to the importance of science to the country’s future, and that’s how I’ve come to it now. So I don’t pretend any scientific knowledge but I do I think understand it’s importance to Britain’s future.

What do you think are the virtues of science?

For the future of the British economy, it is as important as economic stability. If we do not take the opportunities that are there for us in science then we are not going to have a successful modern economy. We will be outcompeted on labour costs: you can export capital and technology anywhere. It is our human capital that is the most important and it is at the cutting edge of science that our human capital can be most exploited for the country’s future.

We’ve got to give the country a great deal more confidence about science and it’s place in the future. I first talked about this a few years back, and everything I have seen here and around the world has only increased my sense of its importance.

Many scientists get in to science because of what they can discover about the universe. Do you follow this side of science at all?

One of the reasons we have more than doubled the science budget, why we have introduced the research and development tax credit, and why we encourage so much the link between the academic and business world, is because Britain has been very good at invention and discovery and not so good at its commercial exploitation. For me, those two things go together.

How do you bridge the gap between science as an academic interest-discovering more about the universe-and science as an commercial enterprise?

You need a certain amount of pure research, and the excitement and creativity of scientific discovery. But if you also have universities and research centres sufficiently in tune to what is going on in the private sector, then hopefully discoveries will be made that have a real utility. In areas like climate change and the biosciences, we should be the lead nation. We have a lot of strengths in science and we have to build those. I’d like to see us getting high quality science teachers in schools, and also having businesses getting involved in how science is taught in the classroom.

How do you get more schoolchildren inspired by science?

I would like to see some of the leading entrepreneurs in the scientific field-both academics and business people-going into the schools and giving children a sense of excitement, not just about scientific discovery but also about the huge job opportunities in science today. In environmental technology we’ve gone from a few years ago 150,000 people employed in the field to almost half a million, and these people are going to make money.

The tendency when I was at school was to see science as something that “the boffin” did and business as something the hard-headed person did. Today there is an interaction between the business and academic worlds, and we should be intensifying that.

Is there a danger in making science close to business that you lose that sense of scientists as impartial-or is that idea past its time?

The more enthusiasm and inspiration you get around science, the more people realise that there are practical applications of science that are immensely exciting and rewarding, that generates support for the whole field of science. There are difficult issues to do with conflicts of interest that come up from time to time but I think that pales into insignificance given the huge boost that comes from science, for example when developing practical ways of meeting challenge of climate change.

The contribution that British industry makes towards research and development is considerably lower than in many other European countries and the US. How do you convince industry to pick up the challenge?

You need to convince them with the vision of business opportunities for the future. It is one reason why we’ve taken such a lead role on the climate change issue, other than the obvious reason to protect the climate. The government has made a big extra investment in science. We aren’t doing as well as we should, on the other hand there are improvements happening.

The research and development tax credit is worth almost two billion pounds now, and some industries such as pharmaceuticals are big investors here. Research and development is the future economically for the country. Over time, this is something we can put right.

You’ve been in power during two extraordinary science-related occurrences: the refusal of people to accept GM crops, and the refusals of parents to have their children vaccinated with the MMR vaccine. What have you taken away from those experiences?

The first is to be very careful about the media and its reporting of these things. The reporting of MMR was disgraceful. There was no real scientific basis for the allegations that were made and it’s caused a great deal of difficulty.

GM, I think, is a different issue. We’ve also had stem cell research, where the outcome has been rather different and more positive. The lesson I learn is that it’s best to start with the public good. In the GM debate, I used to say to people that a lot of the life-saving drugs now being produced are the product of the same type of science as GM crops. This is why you need scientists to be engaged fully in proper public debate. The public should have confidence in science, and the scientific community has to interact with the public to explain things. Once you explain these things, people at least see another point of view.

You said recently that if America doesn’t want stem cell research, we do. Why do you think George Bush is so wrong here, and do you see any ethical problems with stem cell research?

I think we have taken care of the ethical problems. There obviously are ethical issues to do with it, but I think that if it is the case that done properly and in a controlled way, and we have got all sorts of procedures around it, the fact is it can benefit people’s lives enormously.

But I think that we have approached that in the right way, just in the same way frankly, it is a different type of ethical issue but there are ethical issues about animal testing and you have to get those right and we have got actually the toughest regime in the world now. But on the other hand I have seen myself the experimentation that has been done in order to show how you can save lives through the treatment of heart disease for example and this is something that is right to do.

In certain areas, we seem to be moving further away from rational thought, whether it’s the rise of fundamentalist religious beliefs or the use of unproven alternative therapies. Do you see any shift in this direction?

I don’t. I think most people today have a rational view about science. My advice for the scientific community would be, fight the battles you need to fight. I wouldn’t bother fighting a great battle over, say, homeopathy. It’s not going to determine the future of the world. What is going to determine the future of the world, however, is the scientific community explaining-for example-the science of genetics and how it develops, or the issues to do with climate change. I think most people are prepared to be very rational about these issues.

There is a dimension that concerns and frightens scientists, let alone other people, because as the science progresses there are so many possibilities. I was in California recently seeing something of how genetics will develop in the future, and it is immensely exciting, but it will also raise a lot of issues. There will be massive questions around this. This is why the scientific community, just as it is coming out into the business community, has got to come out and engage in a very strong and deep dialogue with wider society.

I personally think people aren’t anti-science. I think as the stem cell debate showed, people come to a fairly rational point of view. However, I think people will be quite staggered at some of the scientific advances that are going to be possible and it’s important the scientific community is out and actually engaging with the issues.

One subject that is of great concern to scientists is creationism. There has been a suggestion that creationism is being taught in some British schools. What are your views on this?

This can be hugely exaggerated. I’ve visited one of the schools in question and as far as I’m aware they are teaching the curriculum in a normal way. If I notice creationism become the mainstream of the education system in this country then that’s the time to start worrying. As I’ve said, it’s really quite important for science to fight the battles it needs to fight. When MMR comes out, or stem cells, or GM, that’s the time to have a real debate.

What about the other big battle: climate change. Where do you go from here in that fight?

The next step is internationally to get a framework agreed with the major countries with a binding set of agreements for when the Kyoto protocol expires in 2012. I set up this process with the G8 countries plus China, India, Mexico, Brazil, South Africa. The agreements will incentivise private business and industry to go after the scientific and technology solutions. They’re out there, they just need to be developed and brought to market. Getting the right carbon price is absolutely vital for doing this. We should be world leaders in this area, so let’s do that.

How do you do that?

You do that not only through investing in renewables-we’re putting in several hundred million pounds-but also explaining to our business and academic world that there is going to be this opportunity. The same applies, more controversially, if we develop the new nuclear power stations. At least half the European countries are thinking about the next stages of nuclear power. Again, we have expertise in this area and we should develop it. Clean energy, clean coal, renewables, energey efficienty-this is going to be a vast market.

WANT to be the first one on your block to live to 100?

From New Scientist issue 2579 of New Scientist magazine, 25 November 2006, page 19

WANT to be the first one on your block to live to 100? You are in with a fighting chance if you're the first-born child of a young mother.

Natalia Gavrilova and Leonid Gavrilov of the University of Chicago sifted through data gathered on 991 centenarians born in the US between 1875 and 1899 and used US census and Social Security Administration records to reconstruct the family histories of 198 of them, searching for anything they had in common.

It turned out that first-born children were 1.7 times as likely as their siblings to live to be 100. An even stronger predictor of longevity was how young their mother was when they were born. Those whose mothers were less than 25 years old were twice as likely to survive beyond a century.

While the researchers aren't certain why this should be, they suspect younger mothers are less likely to have acquired latent infections during their life that could damage the health of the fetus. Younger mothers may also have better-quality eggs. "If the best, most vigorous maternal ova cells are used first - very early in life - this could explain why particularly young mothers produce particularly long-lived children," Gavrilov says.

The results were presented at a meeting of the Gerontological Society of America in Dallas, Texas, this week.

'Don't fall for the cult of immortality' Olshansky

'Don't fall for the cult of immortality'

says S Jay Olshansky in a reply to the de Grey article. What do the ancient purveyors of physical immortality all have in common? They are all dead. False promises'

S. Jay Olshansky: "Physical immortality is seductive"

Some 1,700 years ago the famous Chinese alchemist, Ko Hung, became the prophet of his day by resurrecting an even more ancient but always popular cult, Hsien, devoted to the idea that physical immortality is within our grasp.

Ko Hung believed that animals could be changed from one species to another (the origin of evolutionary thought), that lead could be transformed into gold (the origin of alchemy), and that mortal humans can achieve physical immortality by adopting dietary practices not far different from today's ever-popular life-extending practice of caloric restriction.

THE ALTERNATIVE VIEW I think the first person to live to 1,000 might be 60 already Aubrey de Grey Read full article

He found arrogant and dogmatic the prevailing attitude that death was inevitable and immortality impossible.

Ko Hung died at the age of 60 in 343 AD, which was a ripe old age for his time, but Hsien apparently didn't work well for him.

The famous 13th Century English philosopher and scientist, Roger Bacon, also believed there was no fixed limit to life and that physical immortality could be achieved by adopting the "Secret Arts of The Past". Let's refer to Bacon's theory as SATP.

According to Bacon, declines in the human lifespan occurred since the time of the ancient patriarchs because of the acquisition of increasingly more decadent and unhealthy lifestyles.

What do the ancient purveyors of physical immortality all have in common? They are all dead. S Jay Olshansky

All that was needed to reacquire physical immortality, or at least much longer lives, was to adopt SATP - which at the time was a lifestyle based on moderation and the ingestion of substances such as gold, pearl, and coral - all thought to replenish the innate moisture or vital substance alleged to be associated with aging and death.

Bacon died in 1292 in Oxford at the age of 78, which was a ripe old age for his time, but SATP apparently didn't work well for him either.

Physical immortality is seductive. The ancient Hindus sought it, the Greek physician Galen from the 2nd Century AD and the Arabic philosopher/physician Avicenna from the 11th Century AD believed in it.

Alexander the Great roamed the world searching for it, Ponce de Leon discovered Florida in his quest for the fountain of youth, and countless stories of immortality have permeated the literature, including the image of Shangra-La portrayed in James Hilton's book Lost Horizon, or in the quest for the holy grail in the movie Indiana Jones and the Last Crusade.

What do the ancient purveyors of physical immortality all have in common? They are all dead.

Prophets of immortality

I was doing a BBC radio interview in 2001 following a scientific session I had organised on the question of how long humans can live, and sitting next to me was a young scientist, with obviously no sense of history, who was asked the question: "how long will it be before we find the cure for ageing?"

Roger Bacon thought immortality lay in the Secret Arts of The Past

Without hesitation he said that with enough effort and financial resources, the first major breakthrough will occur in the next 5-10 years.

My guess is that when all of the prophets of immortality have been asked this question throughout history, the answer is always the same.

The modern notion of physical immortality once again being dangled before us is based on a premise of "scientific" bridges to the future that I read in a recently published book entitled Fantastic Voyage by the techno-guru Ray Kurzweil and physician Terry Grossman.

They claim unabashedly that the science of radical life extension is already here, and that all we have to do is "live long enough to live forever".

What Kurzweil and others are now doing is weaving once again the seductive web of immortality, tantalising us with the tale that we all so desperately want to hear, and have heard for thousands of years - live life without frailty and debility and dependence and be forever youthful, both physically and mentally.

The seduction will no doubt last longer than its proponents.

'False promises'

To be fair, the science of ageing has progressed by leaps and bounds in recent decades, and I have little doubt that gerontologists will eventually find a way to avoid, or more likely delay, the unpleasantries of extended life that some say are about to disappear, but which as anyone with their eyes open realises is occurring with increasing frequency.

There is no need to exaggerate or overstate the case by promising that we are all about to live hundreds or even thousands of years.

The fact is that nothing in gerontology even comes close to fulfilling the promise of dramatically extended lifespan, in spite of bold claims to the contrary that by now should sound familiar.

What is needed now is not exaggeration or false promises, but rather, a scientific pathway to improved physical health and mental functioning.

If we happen to live longer as a result, then we should consider that a bonus.

S Jay Olshansky is a professor at the School of Public Health, UIC and author of The Quest for Immortality.

Read Cambridge geneticist Aubrey de Grey's alternative view