Friday, October 7, 2016

Science journals: Anything for a headline

Well, this week's sensational result is reported in the Oct 5 Nature in a paper about limits to the human lifespan. The unsensational nature of this paper shows yet again how Nature and the other 'science' journals will take any paper that they can use for a cheap headline.  This paper claims that the human life span cannot exceed 115 (though the cover picture in a commentary in the same issue is a woman-- mentioned in the paper itself--who lived to be substantially older than that!).  The Nature issue has all the exciting details of this novel finding, which of course have been trumpeted by the story-hungry 'news' media.

In essence the authors argue that maximum longevity on a population basis has been increasing only very slowly or not at all over recent decades.  It is, one might say, approaching an asymptote of strong determination. They suggest that there is, as a result of many complex contributing factors-of-decline, essentially a limit to how long we can live, at least as a natural species without all sorts of genetic engineering.  In that sense, dreams of hugely extended life, even as a maximum (that is, if not for everyone), are just that: dreams.

This analysis raises several important issues, but largely ignores others.  First, however, it is important to note that virtually nothing in this paper, except some more recent data, is novel in any way.  The same issues were discussed at very great length long ago, as I know from my own experience.  I was involved in various aspects of the demography and genetics of aging, as far back as the 1970s.  There was a very active research community looking at issues such as species-specific 'maximum lifespan potential', with causal or correlated factors ranging from the effects of basic metabolism, or body or brain size.  Here's a figure from 1978 that I used in a 1989 paper

There was experimental research on this including life-extension studies (e.g., dietary restriction) as well as comparison of data over time, much as (for its time) the new paper.  The idea that there was an effective limit to human lifespan (and likewise for any species) was completely standard at that time, and how much this could be changed by modern technologies and health care etc. was debated. In 1975, for example (and that was over 40 years ago!), Richard Cutler argued in PNAS that various factors constrained maximum lifespan in a species-related way.  The idea, and one I also wrote a lot about in the long-ago past, is that longevity is related to surviving the plethora of biological decay processes, including mutation, and that would lead to a statistical asymptote in lifespan.  That is, that lifespan was largely a statistical result rather than a deterministically specified value.  The mortality results related to lifespan were not about 'lifespan' causation per se, but were just the array of diseases (diabetes, cancer, heart disease, etc.) that arose as a result of the various decays that led to risk increasing with duration of exposure, wear and tear, and so on, and hence were correlated with age.  Survival to a given age was the probability of not succumbing to any of these causes by that age.

This paper of mine (mentioned above) was about the nature of arguments for a causally rather that statistically determined lifespan limit.  If that were so, then all the known diseases, like heart disease, diabetes, cancer, and so on, were irrelevant to our supposed built-in lifespan limit!  That makes no evolutionary sense, since evolution would not be able to work on such a limit (nobody's still reproducing anywhere near that old).  It would make no other kind of sense, either.  What would determine such a limit and how could it have evolved?  On the other hand, if diseases--the real causes that end individual lives--were, together, responsible for the distribution of lifespan lengths, then a statistical rather than deterministic end is what's real.  The new paper doesn't deal with these, but by arguing that there is some sort of asymptotic limit, it implicitly invokes some sort of causal, evolutionarily determined value, and that seems implausible.

Indeed, evolutionary biologists have long argued that evolution would produce 'negative pleiotropy', in which genomes would confer greater survival at young ages, even if the result was at the expense of greater mortality later on.  That way, the species' members could live to reproduce (at least, if they survived developmentally-related infant mortality), and they were dispensable at older ages so that there was no evolutionary pressure to live longer.   But that would leave old-age longevity to statistical decay processes, not some built-in limit.

Of course, with very large data sets and mortality a multicausal statistical process, rare outliers would be seen, so that more data meant longer maximum survival 'potential' (assuming everyone in a species somehow had that potential, clearly a fiction given genetic diseases and the like that affect individuals differently).  There were many problems with these views, and many have since tried to find single-cause lifespan-determining factors (like telomere decay, in our chromosomes), an active area of research (more on that below).  We still hunger for the Fountain of Youth--the single cause or cure that will immortalize us!

The point here is that the new paper is at most a capable but modest update of what was already known long ago.  It doesn't really address the more substantive issues, like those I mention above.  It is not a major finding, and its claims are also in a sense naive, since future improvements in health and lifestyles that we don't have now but that applied to our whole population could extend life expectancy--the average age at death--and hence the maximum to which anyone would survive. After all, when we had huge infectious disease loads, hardly anybody lived to 115, and in the old days of research, to which the authors seem oblivious, something like 90-100 was assumed to be our deadline.

The new paper has been criticized by a few investigators, as seen in reports in the news media coverage.  But the paper's authors probably are right that nothing foreseeable will make a truly huge change in maximum survival, nor will many survive to such an extended age.  Nor--importantly--does this mean that those who do luck out are actually very lucky: the last few years or decades of decrepitude may not be worth it to most who last to the purported limit. To think of this as more than a statistical result is a mistake.  Not everyone can live to any particular age, obviously.

The main fault in the paper in my view is the claim in essence to portray the result as a new finding, and the publication in a purportedly major journal, with the typical media ballyhoo suggesting that.

On the other hand....
On the other hand, investigators who were interviewed about this study (to give it 'balance'!) denigrated it, saying that novel medical or other (genetic?) interventions could make major changes in human longevity.  This has of course happened in the past century or two.  More medical intervention, antibiotics and vaccines and so on have greatly increased average lifespan and, in so doing in large populations, increased the maximum survival that we observe.  This latter is a statistical result of the probabilistic nature of degenerative processes like accumulating wear and tear or mutations, as I mentioned earlier.  There is no automatic reason that major changes in life-extending technologies are in the offing, but of course it can't be denied as a possibility either. Similarly, if, say, antibiotic resistance becomes so widespread that infectious diseases are once again a major cause of death in rich countries, our 'maximum lifespan' will start to look younger.

Those who argue against this paper's assertions of a limit must be viewed just as critically as they judged the new paper.  The US National Institute on Aging, among other agencies, spends quite a lot of your money on aging, including decades (I know because I had some of it) on lifespan determination.  If someone quoted as dissing the new 'finding' is heavily engaged in the funding from NIA and elsewhere, one must ask whether s/he is defending a funding trough: if it's hopeless to think we'll make major longevity differences, why not close down their labs and instead spend the funding on something that's actually useful for society?

There are still many curious aspects of lifespan distributions, such as why rodents have small bodies that should be less vulnerable per-year to cancer or telomere degradation etc. that relate to the number of at-risk cells, yet only live a few years.  Why hasn't evolution led us to be in prime health for decades longer than we are?  There are potential answers to such questions, but mechanisms are not well understood, and the whole concept of a fixed lifespan (rather than a statistical one) is poorly constructed.

Still, everything suggests that, without major new interventions that probably will, at best, be for the rich only, there are rough limits to how long anyone can statistically avoid the range of independent risk our various organ systems face, not to  mention surviving in a sea of decrepitude.

One thing that does seem to be getting rather old, is the relentless hyperbole of the media including pop-culture journals like Nature and Science, selling non-stories as revolutionary new findings.  If we want to make life better for everyone, not just researchers and journals, we could spend our resources more equitably on quality of life, and our research resources on devastating diseases that strike early in the lives we already are fortunate to have.

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