Hourglass II: A carnival of biogerontology

Welcome to the second installation of Hourglass, a blog carnival devoted to the biology of aging. The entries are representatives of the excellent (and growing) community of bloggers who are writing about biogerontology, lifespan extension technologies, and aging in general. The inaugural issue of the carnival went up last month.

One of the underappreciated mysteries of aging is how it is coordinated throughout the body. As an animal gets older, its whole body ages; individual organ systems don’t suddenly become decrepit all on their own. Consistent with this, genetic studies of aging have been very successful at finding mutants that either accelerate or delay aging at a system-wide level, but far less successful at identifying mutants with dysregulated coordination of the aging process (imagine, e.g., a mouse with a youthful body and extremely old ears). How does this work? It sounds like a job for a circulating factor that is present throughout the body — and indeed, such factors do indeed seem to play an important role in the determination of lifespan and the temporal coordination of aging throughout the body. At Fight Aging!, Reason reports on multiple aspects of the roles played by the endocrine system in governing aging — and discusses a potential relationship between the mechanisms of life extension by growth hormone deficiency and methionine restriction.

Although the tissues and organs of the body age all age at comparable rates, there is nonetheless considerable heterogeneity at the cellular level. Old and damaged cells enter a permanent growth arrest known as senescence, which is both good (because they can’t initiate tumors) and bad (because persistent senescent cells behave in a ridiculously antisocial manner, secreting growth factors and proteases that both encourage nearby tumors to metastasize and degrade tissue function). Fortunately, senescent cells make up a very small proportion of the overall population, even in very aged tissues — so one could imagine removing them from the body without harm (and, indeed, to great benefit, because removal of these cells would also eliminate senescence-derived secreted factors). Needless to say, the extermination of senescent cells is an active subject of research. At his new site Anti-Ageing Research, Dominick Burton discusses ways in which specifically targeted cancer therapies might be adapted to attack senescent cells instead.

Continuing the theme of connecting cancer and aging, Ward Plunet at BrainHealthHacks asks a timely and important question: Can our track record in cancer research give us a hint of what we can expect in longevity research? In other words, is past performance in research and treatment of a major health issue in any way indicative of how we’re likely to do in addressing the grandmother of all health issues? Like many of Ward’s post, this piece is particularly well-researched and data-rich, so remember to show up with an appetite for information.

We can certainly learn a great deal from our past experiences of large-scale research, but there’s also good deal to be learned from reflection on a more individual scale. At the delightfully named Existence is Wonderful, Anne C. shares a parable about taking care of her friend Nigel the Fish and what that led her to realize about longevity: specifically, that environment is critical, and that the combination of extrinsic factors that one might collectively term “nurture” can make all the difference between a short unhappy life and a long fulfilled one. In her words: “We don’t necessarily know what hard limits are on longevity until we optimize care. I saw a dramatic turnaround in my fish when I learned how to properly configure the tank setup, and I hope to see the day when human medicine makes a similar leap in effectiveness.”

Strongly related to environmental surroundings are lifestyle choices, including the sort of exercise we choose to do. The benefits of physical exercise of all sorts are already well-documented, but it’s becoming increasingly clear that mental exercise will be an essential part of the brain maintenance that must accompany a successful aging process. At SharpBrains, Alvaro Fernandez discusses the Top Ten Brain Training Future Trends, including the idea that creative uses of cognitive training metrics might someday be used to allow early detection of neurodegenerative diseases such as Alzheimer’s.

That’s a wrap for this installation. Hourglass III will be hosted on September 9th by Alvaro at SharpBrains, and Hourglass IV on October 14th by Anne at Existence is Wonderful. We’ll set up a standalone email address and archive page for the carnival at some point — but for now, if you have submissions (or want to volunteer to host the carnival), please email me and I will forward them to the current host.

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14 comments

  1. Hmm, Brainhealthhack’s article doesn´t examine throughly enough the data, I think. For one, the article opening presents three causes of mortality, but examines only the progress in one (It could be argued that decreases in cardiovascular mortality have resulted in people surviving to develop cancer). Also, in cancer itself, most of his tables are concerned with survival rates unadjusted by age (if, for instance, in l950 we had 20 people dying with cancer, and now we still do, )

    In fact, in this website you can see that there has improvement of survival in cancer patients over time:
    http://info.cancerresearchuk.org/cancerstats/survival/fiveyear/?a=5441

    Also, I find it odd that, in his opening statistics he points out the little relative improvement in death rate between l950 and 2002, and l950 and 2005, without considering the significative improvement from 2002 to 2005.

    Finally, he states that the increase in life expectancy from l950 are owed mostly to decreases in infant mortality. I cannot point the source (as I dont recall it), but I read somewhere that this was in fact true until l950, and afterwards there was a fall in elderly death rates as well.

    Just some observations.

  2. typo: where “(if, for instance, in l950 we had 20 people dying with cancer, and now we still do, )”

    it is supposed to continue: “yet back then they died at 60, and now they die at 80, it shows there has been an improvement”

  3. Brainhealthhack’s article does give quite a bleak outlook for medical research.
    However, after seeing/reading so much overdramatized, exaggerated news about medical ‘breakthroughs’, I sympathize with Brainhealthhack’s view, and think that many of those claims, especially those from big pharmaceutical companies, promise big but deliver small.
    It seems to me that everyone wants and are waiting for ‘the magic drug’ that cures all diseases or extend lifetime. But a simple although difficult to do change in lifestyle is already known to extend longevity – diet restriction. I, for one, have extreme trouble in keeping to this lifestyle though…..

  4. Hm. I sympathize with the frustration at the apparently slow advance rate (through this is a relative thing), and the tendence from some people to hype their findings. The latter has an obvious reason: even if profittable drugs, or products, are not really “just a few months away” from a line of research, scientists must make it look like it does, if they want funding to keep it up (and eventually reap those benefits). There is a precedent for this: during the eighties many researchers hyped their results in genetic engineering and whatnot, and for ten years there were cases of companies that funded the wrong thing and went bankrupt. But after that period, the ones which got lucky, and had financed things that gave results, such as insulin-producing organisms, became filthy rich.

    I think we are in a simmilar position right now. Scientists hype their results to reap more funding, are cautious with clinical applications to avoid problems that could result in big backslashes (remember what happened to gene therapy funding after some of the treated bubble kids developed leukemia?).

    That being said, there *are* things being done now that are producing actual results, not merely showing promise in a few isolated experiments. Transplant tollerance, for instance. Six years ago this was treated as a “holy grial” myth in medicine textbooks, and today is a reality (if a Phase II-III one 😉 ). It´s not alone, either. Look at the batteries of new drugs for alzheimer treatment that are being unfolded, with varying degrees of efficacy. Look at cancer immune therapies. In the “promising, but not on clinical trial yet”, there´s the whole RNA interference field. It is being used in vivo for various experiments, and there are already plans to treat maladies with it. And this is leaving aside the “interesting and promising experiments, but without practical applications just yet” (such as stem cell vascular growth in vivo -an experiment which should be combined with Sangamo´s artificial transcription factors to try to guide it, IMHO, and others). No, medical science is far from still. Great things have been done, and are being done. And I think that this is just the peak of the iceberg. What will come out of all this? Time will tell. (If we knew from beforehand what will a line of research yield, there wouldn´t be a need for research in the first place, right?)

  5. *as a PD: progress is being done, and HAS been done. I mentioned earlier cancer survival rates. Compare the early artificial hearts from 20 years ago, which needed to be fit in the abdominal cavity (due to their size) to modern ones, which can fit in the chest. And to the ones which are pending for approval. There´s one in particular which is a small turbine that cardiac surgeons plan to install in CCI-afflicted but still functional hearts, as to lend them strenght, and prevent further degeneration (and possibly give breathing space to undergo treatment of the condition).

  6. I agree, there’re lots and lots of good medical research going on and useful inventions coming out of them. And medical research should be placed on high priority in any healthy society.

    However, don’t you think there’s something wrong with the way we do research?

    As you know very well as a PhD, the current situation with funding forces everyone to be overly generous when describing our findings and the implications that can be derived from these data. And in today’s advertisement-overloaded world, we are made to believe many things that are actually not true.

    A real life example is when a friend of mine told me she would save up cord blood for her son. I’ve heard good things about cord blood transplant and thought it must be a good idea. However, a little web-surfing made me realize that private cord blood banking is in fact quite controversial.
    (An example of the websites I’ve visited,
    http://www.lrf.org.uk/en/1/discbbstd.html
    )
    In stark contrast, from the websites of those private cord blood banking service providers, wow, they want you to believe that cord blood is the future cure for blood-related diseases, alzheimer and other old age diseases, etc etc etc. They absolutely do not tell you the downside – many of those diseases claimed to be curable with cord blood are actually in their preliminary stage of research, maybe only tested in a few animal studies, not even clinical stage; and the chances that the child will actually use the cells are very slim.
    I’m just amazed by how quickly someone can make use of a medical research finding to generate such big bucks! Many of those commercialized products of medical research are not backed up by sufficient data.

    Also, I find this article (although a little old) about stem cell therapy a good wake-up call for many,
    http://www.sciencemag.org/cgi/content/full/313/5784/160

    I enjoy being a researcher very much and that’s why I’m still here. BUT, the same question – don’t you think there’s something wrong with the way we do research right now? Or maybe more appropriately, with the way we interpret our results and present it to the public?

    As a scientist, and someone who receive tax payer’s money, don’t we have the responsibility to alert the public about misuse of scientific findings? And to be more critical of any ‘breakthrough’ that comes out of medical researches?

  7. (Disclaimer, I´m a student at Medical School, not a PhD. :-)).

    I do think that healthcare professionals have a duty towards the public, to inform them of what works and what doesn’t, and warn against dubious initiatives (particularily when there’s a lot of money involved). I dont think that doing public service announcements will erradicate trickery in healthcare, through.

  8. and for the record, I do think there’s something wrong with a system that incentivates deceit at publishing results (I read an a while back that stated that most research studies shifted the goalposts they had set while designing the experiment at the time of writing the article to be published, as to make it seem more successful. (I guess the extreme example of this would be Hwang Woo Suk and his fake claims of human clonation)

    Maybe the problem is in how people, and the industry perceives research? It seems to me it is expected that a given research line will yield the expected results timely, and if it gets delayed, it must be the fault of the researchers somehow. Maybe increasing public awareness of the uncertainities of R&D would help. On the other hand, that might bring it´s own problems of a potential lack of investments.

  9. Mstudent,

    thanks for your comments regarding cancer and longevity – and you make some important points.

    You correctly point out that we have made gains in reducing death from heart disease (which I mention in the piece)- from 1950 to the current time, but it you look at the data from 1900 it looks like it is roughly the same as now (there might be a problem with the accuracy of data from so long ago – but it was published in a peer reviewed article). I decided to concentrate on cancer since I was so surprised by the data when I looked at it, and due to the fact that several of my friends had cancer – so it was more personal to me. It could also be argued (as is done by longevity researchers) is it doesn’t matter if you only solve one of the problems (e.g heart disease) if you just die of another (cancer). That is partially why longevity research is so important – to work it has to treat the entire organism – not an isolated disease.

    You also make a good point that the 5 year survival rate has improved for some cancers. And that is why I was so surprised when you look at the cancer death rate (age adjusted per 100,000 people) that we have not made such great strides. Partially due to an increase in cancer rate overall (though read my piece for greater explanation). But also it really depends on what are the most prevalent cancers and which are the most deadly for the overall death rate.

    All the data I presented were all age adjusted (the only way to compare across different years – which I mention early in the piece).

    You also point out the gains from 2002 to 2005, but I am not really sure if the 2005 rate is statistically different than 1950. It might be – but I am still surprised by how little it has changed – despite all the great advances we have made in biology and all the constant announcement of cancer cures.

    Your final point regarding the improvements in infant mortality not accounting for all the gains in our increased lifespan – I am open to that possibility. I have found no concrete data either way regarding this matter. I am hoping one of the readers will point us to the data.

    Finally, I want to point out I am a strong proponent of longevity research and I want us to make advances and improve the health and lifespan of all of us. That is why I was so surprised by the data I found regarding cancer – though I am open to being wrong about my interpretation of the data.
    I was hoping my piece stirs us to work harder because all the major causes of death are difficult biological problems to solve and so is longevity. I am hopeful of future research – but we need to be realistic where we currently stand.

    Hopefully
    Ward
    brainhealthhacks.com

  10. I fully agree with the need of grasping the current situation is vital to make plans. However, I´m unsure that comparing a single type of data leads to definite conclusions. As you say, it is surprising to see how cancer death rates are more or less stable, despite the progress done.

    -One possible cause is, as I said, that by doing the age adjustment you cloak the effect of survival rates. Maybe the same number of people are dying of cancer, but maybe they are dying of it LATER on, either by surviving it longer, or by recidives, or by other sorts of cancer (for instance, hematological tumor survivors show an increased risk to other hematological tumors later on.

    -There´s another factor, that you mention in the article in fact: Lung cancer is the most freçuent cause of cancer related death (around l/6). But I think that it deserves special attention. Lung cancer is hard to detect, and 76% of the cases are detected after it has spread (37% to lymphatic nodes, 39% with methastasis), with so far few ideas for better screening (I´ve read a few times about purpoted blood tests for LC, one by a French doctor,other by a company called Gaithseburg pharmaceuticals, and another by one Anil Vachani, but so little has been said afterwards that I´m suspicious about how sensitive and specific they actually were). This places a big handicap in lung cancer improvements, as in general, but particularily in earlier dates (bear in mind that chemotherapy -like transplants- only began to be operative around 65′-’75), the effectiveness of treatment is determined by the stage.

    Even so, it´s worthwhile to point out that the survival rate at one year from diagnosis rose from l3 in ‘7l to 26% in 2000 (I haven´t found a 5-year survival rate for l970, but for 2002 it´s l5%). There HAS been progress. It´s still far from impressive, but it has moved.

    – An eye should on cardiovascular death rate while looking at cancer, as it might have decreased in “favour” of the cancer death rates.

    – As for decreased death rates for late age, I read *somewhere* (for the life of me I can´t recall where 😦 ) that since l96x, they have been dropping l,5% annually.

    Finally, I think that the negative outlook you take at the end of the article is a bit of a case of “the trees concealing the forest”. True, people have still been dying of cancer these last 50 years (for that matter, they have been dying of other things as well), but the situation has surely progressed.

    As for future improvements (in healthcare, or cancer, or whatever), I think there is reason for optimism, but in this topic I always get reminded of that joke, where a wealthy man spending his holidays in the country, asks a sheepherder to tell him what kind of weather does a certain sky-color forecast (presumably, using traditional, infallible, ages-old peasant lore), to which the sheepherder answers (while chewing a twig) “Well, it could mean that it´s going to rain… or it could mean that tomorrow it will be a sunny day. It mostly depends on what the weather will be the next day, you know..”
    Which I think sums up the çuid of the matter: in the end, tomorrow will tell what will come tomorrow.

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