Monday, July 27, 2009
Sunday, July 26, 2009
Naturenews has this story on the potential progress being made with heart regeneration. Here is a sample:
With a little prompting, adult hearts may be able to heal themselves — at least, they may do if a recent study in mice holds true for humans. The heart has long been considered one of the organs least capable of regenerating after injury, with heart transplants one of the few effective therapies available. But now a team led by Bernhard Kühn at the Children's Hospital and Harvard Medical School in Boston, Massachusetts, has shown that protein injections in mice not only prompt heart muscle cells, known as cardiomyocytes, to proliferate, but that this proliferation also reduces damage after a heart attack.
Thursday, July 23, 2009
QJM Paper Now Published
My paper "Towards a more inclusive vision of the medical sciences" is now available in the August issue of QJM: An International Journal of Medicine. Here is the abstract:
Progress in the medical sciences is largely determined by two things: (i) the questions we ask, and (ii) how rigorously and vigorously we attempt to answer them. How do we know which questions are the right questions to ask, and thus the correct questions to spend our time and energies trying to answer? Such evaluative concerns bring into sharper focus the question—‘What is medicine for?’ The international study of rosuvastatin is important not simply because of the health benefits it may confer, but because it inspires a more robust and inclusive vision of the medical sciences. A vision which recognizes that the primary goal of medicine is to promote health, and that includes the health of ‘normal’ people as well as those with illness and disease. This inclusive vision of the medical sciences is a transformative one, it departs from the ‘disease-model’ approach which has dominated distinct areas of medical research for decades.
And a brief excerpt:
So what questions might we supplement the study of specific diseases with? If the delivery of health is our primary concern, and ageing threatens the health prospects of a population, then the obvious question is—what causes ageing? Evolutionary biology now provides scientists with new tools for understanding the ultimate, and not just proximate, cause of morbidity and mortality (as well as survival). Rather than invoke an overtly idealized concept of health—where health is equated with the absence of disease—evolutionary medicine incorporates the physiological constraints and ranges of plasticity well documented by the biological community.10 And this permits us to understand the role natural selection plays in survival and death and disease. By addressing the ultimate causes of phenotypes like disease and health, we begin to gain a better understanding of the things that threaten the health prospects of ageing populations.
....Like a diversified economy and economic prosperity,a diversified study of disease and health will best secure the goal of human flourishing. The reality is that the vast majority of ‘normal’ people are susceptible to the chronic illnesses of ageing (e.g. cancer and heart disease). To meet the health challenges of an ageing world we must adopt a more inclusive approach to preventative medicine, one that includes the drug development of interventions in the ageing process itself.17,18 Treating specific diseases and illness is of course important as well. But a truly inclusive vision of the medical sciences encourages us to adopt a more bold and imaginative conception of human flourishing and medicine. And humanity deserves nothing less than the best the medical sciences can deliver.
Thursday, July 16, 2009
Nature Study on Rapamycin and Lifespan of Mice
The most exciting and important field of science today is aging research. Understanding why we age- and become vulnerable to all the diseases that accompany aging (like cancer, heart disease, arthritis, AD, stroke, etc.)- could lead to the development of a drug that retards aging. Thus providing humans with the opportunity to enjoy better health in late life (and more years of health) by delaying the chronic diseases of aging.
The latest issue of Nature has this exciting study about the molecule rapamycin [first discovered in soil samples on Easter Island, hence the picture] which had previously been shown to extended the lifespan of invertebrates. But what about mammals? This new study shows it also extends the lifespan of mice. Here is the abstract:
Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies1; however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.
And a small sample from the article:
Because incidences of most diseases rise rapidly with age, interventions that delay ageing would greatly benefit health. So far, dietary additives that delay ageing and increase lifespan in rodent models have shown only weak effects. Before clinical studies are considered, anti-ageing interventions must be repeatable and effective in many mouse genotypes, and not merely postpone strain-specific diseases.
....It is especially noteworthy that rapamycin feeding can extend mouse lifespan even when started late in life; in terms of the percentage of the maximal lifespan, a 600-day-old mouse is roughly the equivalent of a 60-year-old person14. An effective anti-ageing intervention that could be initiated later than the midpoint of the lifespan could prove to be especially relevant to clinical situations, in which the efficacy of anti-ageing interventions would be particularly difficult to test in younger volunteers. Our data justify special attention to the role of the TOR pathway in control of ageing in mammals and in the pathogenesis of late-life illnesses.
And there is also a News and Views feature on the study here. A sample:
The small molecule rapamycin, already approved for clinical use for various human disorders, has been found to significantly increase lifespan in mice. Is this a step towards an anti-ageing drug for people?
Anti-ageing drugs — compounds that slow the hands of time and allow humans to live far beyond their natural span — have long been fertile ground for science-fiction writers. More recently, however, the possibility that such compounds might exist, and might perhaps even be within reach, has gained scientific credibility. In this issue (page 392), Harrison et al.1 provide evidence that pharmacological intervention in the ageing process is feasible in mammals. They report that dietary supplementation with rapamycin — a compound known to be linked to lifespan in invertebrates — significantly increases the lifespan of mice.
....Is this the first step towards an anti-ageing drug for people? Certainly, healthy individuals should not consider taking rapamycin to slow ageing — the potential immunosuppressive effects of this compound alone are sufficient to caution against this. On the basis of animal models, however, it is interesting to consider that rapamycin — or more sophisticated strategies to inhibit TOR signalling — might prove useful in combating many age-associated disorders. Also, as relevant downstream targets of TOR are better characterized, it may be possible to develop pharmacological strategies that provide the health and longevity benefits without unwanted side effects. So, although extending human lifespan with a pill remains the purview of science-fiction writers for now, the results of Harrison et al. provide a reason for optimism that, even during middle age, there's still time to change the road you're on.
Monday, July 13, 2009
Economist Article on Global Aging
Following on from the themes of my previous post on "The Folly of Our Times", The Economist has this excellent article on the real challenge for humanity this century- global aging. Here is an excerpt:
STOP thinking for a moment about deep recession, trillion-dollar rescue packages and mounting job losses. Instead, contemplate the prospect of slow growth and low productivity, rising public spending and labour shortages. These are the problems of ageing populations, and if they sound comparatively mild, think again. When the IMF earlier this month calculated the impact of the recent financial crisis, it found that the costs will indeed be huge: the fiscal balances of the G20 advanced countries are likely to deteriorate by eight percentage points of GDP in 2008-09. But the IMF also noted that in the longer term these costs will be dwarfed by age-related spending. Looking ahead to the period between now and 2050, it predicted that “for advanced countries, the fiscal burden of the crisis [will be] about 10% of the ageing-related costs” (see chart 1). The other 90% will be extra spending on pensions, health and long-term care.
The rich world’s population is ageing fast, and the poor world is only a few decades behind. According to the UN’s latest biennial population forecast, the median age for all countries is due to rise from 29 now to 38 by 2050. At present just under 11% of the world’s 6.9 billion people are over 60. Taking the UN’s central forecast, by 2050 that share will have risen to 22% (of a population of over 9 billion), and in the developed countries to 33% (see chart 2). To put it another way, in the rich world one person in three will be a pensioner; nearly one in ten will be over 80.
This is a slow-moving but relentless development that in time will have vast economic, social and political consequences. As yet, only a few countries with already-old populations are starting to notice the effects. But labour forces are now beginning to shrink and numbers of pensioners are starting to rise. By about 2020 ageing will be plain for all to see. And there is no escape: barring huge natural or man-made disasters, demographic changes are much more certain than other long-term predictions (for example, of climate change). Every one of the 2 billion people who will be over 60 in 2050 has already been born.
Some more food for thought on why global aging is a much more pressing problem than climate change: (1) the likelihood of the former is much, much higher than the latter; (2) the consequences of the former will be much, much more severe than the latter (in terms of causing disease and straining economies); and (3) there is a much sounder scientific basis for believing we could actually do something to mitigate the rate of aging than intentionally alter the global temperature.
Sadly, championing the cause of better health and prosperity for all via age retardation is not as fashionable as the expensive and unsound aspiration to play "climate gods". More people care about feeling like they are making the world a better place (and about being perceived as caring) than about actually making the world a better place. This impedes serious progress on the problems humanity faces this century.
Thursday, July 09, 2009
CR Study in Monkeys
The long awaited (20 years!) results of this study are finally out. The latest issue of Science has the scoop here. Here is the abstract:
Caloric restriction (CR), without malnutrition, delays aging and extends life span in diverse species; however, its effect on resistance to illness and mortality in primates has not been clearly established. We report findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research. In a population of rhesus macaques maintained at the Wisconsin National Primate Research Center, moderate CR lowered the incidence of aging-related deaths. At the time point reported, 50% of control fed animals survived as compared with 80% of the CR animals. Furthermore, CR delayed the onset of age-associated pathologies. Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy. These data demonstrate that CR slows aging in a primate species.
The NY Times has the story here. Here is an sample:
A long-awaited study of aging in rhesus monkeys suggests, with some reservations, that people could in principle fend off the usual diseases of old age and considerably extend their life span by following a special diet.
....Dietary restriction seems to set off an ancient strategy written into all animal genomes, that when food is scarce resources should be switched to tissue maintenance from breeding. In recent years biologists have had considerable success in identifying the mechanisms by which cells detect the level of nutrients available to the body. The goal is to find drugs that trick these mechanisms into thinking that famine is at hand. People could then literally have their cake and eat it, too, enjoying the health benefits of caloric restriction without the pain of forgoing rich foods.
The Folly of Our Times
In the immediate aftermath of 9/11, few dissenters voiced their opposition to the unsubstantiated and disproportionate response of the Bush Administration. Measures like the Patriot Act passed virtually unopposed with little critical debate. So to for the invasion of Afghanistan... then Iraq... Over time some dissenters voiced concerns, then more, and more. But while dissent slowly grew, many lives were lost and Bush drove the American economy into the ground.
With the benefits of hindsight, many would now agree with those who initially dissented from the Bush response to 9/11 and probably wished those dissenting voices had been louder. But we cannot go back and change history. But we can change our future actions. And that is why I have decided to write this post.
The folly of our times today is that this story dominates the headlines and public policy while this story, which addresses what really is the greatest challenge facing humanity this century, is ignored.
Rather than championing the unrealistic, unproven, and extremely expensive goal of trying to control the uncontrollable (i.e. the temperature), those who want to promote the health and economic prospects of the world's population ought to champion realistic, proven and cost-effective ways of combating disease and poverty.
The greatest threat to humanity comes not from the weather, but from the evolutionary neglect that has left our species vulnerable to the chronic diseases of aging. And the solution to humanity's greatest challenge today lies not in measuring ocean temperatures and monitoring ice caps and polar bears, but understanding the chronic diseases (like cancer and heart disease) that kill millions every year. It is vital that public policy be premised on the facts and sound science. Unfortunately "Panic! Governance" prevails.
If the promises made by the politicians at the G8 are to be believed, they have committed their countries to the largest, most expensive, scientific experiment in human history. Make no mistake about it, this is an *experiment*. Furthermore, it is the first time this experiment has ever been done (no clinical trials have been run). And thus it is important to ask: what is the reasonable attitude to take towards such an experiment?
Consider this hypothetical. Imagine your next door neighbour (who is a scientist that studies aquatic ecosystems) told you that he was planning to do an experiment that, if successful, could control the local temperature in your city next week. He promises to ensure that the weather next Sunday would be sunny and between 23- 25 degrees (ideal for his golfing tournament). The only problem is he needs help getting funding to try his experiment out. He asks you to lend him $3000. What would you say?
Well, the leaders of the developed world have just made you a similar proposal. Granted their intentions are more laudable than that in my hypothetical example, but the cost is much, much higher and the scientific basis for believing the real experiment would work is not substantially higher than in my hypothetical example.
No doubt many would contest my last point. But the reality is that there is no scientific basis (i.e. based on actual experiments) for believing that the proposed global experiment will work the way people hope it will. We do not know what the consequences of a reduction on greenhouse-gases will be on the planet. Why don't we know? Because there are many variables at play here and we have never done this before (and if anyone claims they have, it would be interesting to know what planet they did this experiment on and when!).
To help people think sensibly about what their attitude towards climate science should be, consider your attitude towards two other laudable aspirations- eliminating cancer and securing economic prosperity. Unlike experiments involving cancer drugs or economic policies (which, as we all know, do not always have the consequences experts hope for), we have never undertaken a climate experiment before. So we have no track record to base our faith in this science on. This means the amount of faith we do have should be less than the faith you invest in the latest cancer drug or economic stimulus package rolled out by government. How many drug sceptics and economic sceptics are there out there? Well, you have even less of an empirical basis for believing what most environmentalists promise you. So pick your sceptical attitudes wisely! When there is no evidence the benchmark should be scepticism. That applies to unproven drugs, untried economic policies and climate policies.
Controlling the global temperature is much more grandiose than trying to control tumours or the economy. Furthermore, numerous experiments have been done on cancer and the economy. We have evidence that some things work pretty well against cancer and some things don't. But climate science is a virgin science. There are no past experiments we can turn to to reassure us that the intended consequences of this first (and most expensive) experiment of its kind in human history will be a success (nor is it possible to confirm or disconfirm that it was a success in a 100 years time!).
When it comes to an experiment that has never been done before we should all have a sceptical attitude, especially with something as complex as the climate. "But what about helping the poor?" you ask. I'm all for that! So let's pursue the more immediate, probable and cost-effective measures that will help promote the health and economic prospects of those in the developing world.
What science might help the world be a better place? Well, for starters it would help if Charles Darwin's scientific contributions had 1/10th the policy influence that Al Gore's contribution has had!
Wednesday, July 08, 2009
CR, Reproduction and Exercise
The latest issues of Journal of Gerontology: Biological Sciences and Medical Sciences (see here) have a interesting mix of articles that reveal how complex the aging process is and the different interventions that can impact health and longevity. I will briefly note three here.
This study examines the impact calorie restriction has on mice during different periods of their lifespan. Here is the abstract:
Life span can be extended in rodents by restricting food availability (caloric restriction [CR]) or by providing food low in methionine (Meth-R). Here, we show that a period of food restriction limited to the first 20 days of life, via a 50% enlargement of litter size, shows extended median and maximal life span relative to mice from normal sized litters and that a Meth-R diet initiated at 12 months of age also significantly increases longevity. Furthermore, mice exposed to a CR diet show changes in liver messenger RNA patterns, in phosphorylation of Erk, Jnk2, and p38 kinases, and in phosphorylation of mammalian target of rapamycin and its substrate 4EBP1, HE-binding protein 1 that are not observed in liver from age-matched Meth-R mice. These results introduce new protocols that can increase maximal life span and suggest that the spectrum of metabolic changes induced by low-calorie and low-methionine diets may differ in instructive ways.
A second study examines the hypothesis that late female fertility and slow somatic aging may be promoted by the same genetic variants. Here is the abstract:
Women giving birth at advanced reproductive ages in natural fertility conditions have been shown to have superior postmenopausal longevity. It is unknown whether improved survival is more likely among relatives of late-fertile women. This study compares survival past age 50 of men with and without a late-fertile sister in two populations: Utahns born in 1800–1869 identified from the Utah Population Database and Québec residents born in 1670–1750 identified from the Programme de recherche en démographie historique. Male survival was greater for those with, rather than without, a sister reproducing after age 45, particularly among men with at least three sisters (Utah rate ratio [RR] = .801, 95% CI = 0.687–0.940; Quebec RR = .786, 95% CI = 0.664–0.931). Survival of wives was unaffected by whether their husbands had a late-fertile sister, suggesting a weak influence of unmeasured socioenvironmental factors. These results support the hypothesis that late female fertility and slow somatic aging may be promoted by the same genetic variants.And finally this study compares the impact physical activity has for end-of-life care. Here is the abstract:
Background: Little is known about the early predictors of need for care in late life. The purpose of this study was to investigate whether physical activity from midlife onward was associated with hospital and long-term care in the last year of life.
Methods: We studied a decedent population of 846 persons aged 66–98 years at death, who, on average 5.8 years prior to death, had participated in an interview about their current and earlier physical activity. Data on the use of care in the last year of life are register-based data and complete.
Results: Men needed on average 96 days (SD 7.0) and women 138 days (SD 6.2) of inpatient care in the last year of life. Among men, the risk for all-cause hospital care in the last year of life was higher for those who had been sedentary since midlife (adjusted incidence rate ratio [IRR] 1.98, 95% confidence interval [CI] 1.14–3.42) compared with those who had been consistently physically active, whereas use of long-term care did not correlate with physical activity history. Among women, the risk for long-term care was higher for those who had been sedentary (IRR 2.03, 95% CI 1.28–3.21) or only occasionally physically active (IRR 1.60, 95% CI 1.06–2.43), than for those who had been consistently active from midlife onward, whereas use of hospital care did not correlate with physical activity history.
Conclusion: People who had been physically active since midlife needed less end-of-life inpatient care but patterns differed between men and women.
Thursday, July 02, 2009
Ventor and Dawkins Video
This video is truly fanscinating and well worth watching.
Venter and Dawkins tour Venter's Institute. It's just amazing how far genetic sequencing technologies have come in just a decade. And computing technology is at the fore of this progress. As Venter puts it in the interview, it's "the industrialization of biology".
Venter estimates that the goal of a $1000 human genome could be achieved in 5 years, which would revolutionize medicine. This video, with two of today's most important scientists, is a real gem and effectively illustrates the incredible speed with which the genetic revolution is progressing.