What's the limit of the human lifespan? And what do World War I veterans have to do with it?

Graph showing lower rate of mortality (blue) in people aged
90-95 versus the rate in people aged 50-55 (orange). Figure
from S.J. Newman (2018) Errors as a primarycause of late-life
mortality deceleration and plateaus. PLoS Biol 16(12):
e2006776. https://doi.org/10.1371/journal.pbio.2006776
An intriguing phenomenon has emerged in recent years: among very old people, the rate at which people die appears to decline when they get past a certain age. In other words, as these authors claimed in their 2011 book, aging slows down and maybe even stops. Or at least the mortality rate levels off past the age of 100, according to another study published earlier this year. This has led some scientists to speculate that the upper limit on human lifespan may be much older than anyone alive today.

Not so fast, says a new study by Saul Newman in PLoS Biology. Newman looked at the data and found something quite different: it's all just a mistake. Well, perhaps not a mistake exactly, but a consequence of many small errors. Let me explain.

In almost all species, mortality rates increase with age. In other words, as you get older, your likelihood of dying in a given year slowly but inexorably increases. Intuitively, we all know this: if young people die, it's tragic because we don't expect it. When people in their eighties and nineties die, it's sad, but no one is really surprised.

The evidence for decreasing mortality among very old humans has emerged from a number of studies that provide seemingly solid evidence that people over 100 die at the same or even lower rates then people between 80 and 90, or between 90 and 100.

Not surprisingly, many people would like to believe that human lifespan is unlimited. Indeed, it's one of the hottest topics in Silicon Valley these days. And perhaps someone will invent some true life-extension technology someday. But Newman's analysis pours cold water on the notion that our natural longevity is unlimited.

One difficulty with studying very old people is that there simply aren't that many of them, so the studies tend to be small. Another problem–and this is what Newman zeroes in on–is that we don't have very good birth records for people over 100 years old. They were born a long time ago, when record keeping wasn't always so good. What if there are a few errors?

It might seem that this shouldn't matter, as long as the errors are random–in other words, as long as people's ages are both under- and over-estimated at the same rates. The problem is that even if the errors are random, they don't play out that way. Here's why.

For the sake of argument, let's imagine a set of people whose true ages are off by 5 years in either direction. (I know that's a lot, but bear with me.) By the age of 100, as Newman points out, virtually no one is alive from the cohort that underestimated their age; these are people who have a true age of 105. But many more will be alive from those who overestimated their age; these are the 95-year-olds who think they're 100.

Newman's paper points out that if only a few people are overestimating their age, this can cause mortality rates to flatten or decelerate–or at least they appear to decelerate, because these people aren't really as old as we (or they) think they are. He then shows, in considerable detail, that only a very small error rate is more than enough to explain all of the apparent decline in mortality rates from recent studies. In other words, the decline in mortality is simply an illusion.

What does World War I have to do with any of this? Newman explains:
"approximately 250,000 youths inflated their ages to enter the 1894–1902 birth cohorts and fight for the United Kingdom in World War I."
The same thing happened in the U.S. and other countries: 16- and 17-year-old boys said they were 18 so they could sign up. Coincidentally, these men would have been around 100 years old when many of the recent studies of centenarians were conducted, and it's very likely that some of these men were included in those studies. It wouldn't take many to distort the apparent mortality rates.

Who could have imagined that these brave young men who signed up to fight for their country (my grandfather was one of them), so many years ago, would have this completely unexpected effect on the science of aging, almost exactly 100 years after the war ended? It seems somehow appropriate that today, as the last veterans of the Great War leave us forever, they can still remind us of their sacrifice.

Russian homeopathy, hiding in plain sight

It turns out that Russia has its very own brand of bogus medicine:"release-active drugs," or RADs. Dozens of scientific articles have been published claiming that these substances can be used to treat or cure a remarkably broad range of illnesses, including:
"... influenza, hemorrhagic fever, meningococcal meningitis, herpes, HIV, diabetes, erectile dysfunction, sleep disorders, obesity, chronic inflammatory joint diseases, attention deficit hyperactivity disorder, ..., alcoholism, allergies, and many other health problems." 
If this sounds too good to be true, that's because it is.

Thanks to a new report published in the journal BMJ Evidence-Based Medicine (provocatively titled "Drug discovery today: no molecules required") we now know that RADs aren't drugs at all, because they don't actually contain anything. As the new study reveals,
"The problem [with RADs] is that typical dilutions of the active ingredient are so high (from 1:1024 to 1:101991) that no molecules of the initial antibodies should be present in the ‘drug’ itself."
In other words, RADs are simply homeopathy by another name. As I've written many times before, homeopathy is one of the most patently absurd forms of pseudoscience, and although it's been debunked countless times, it remains popular due in part to commercial interests that profit handsomely from selling ineffective but expensive sugar pills.

RADs are produced by a single Russian company, with the odd name "OOO NPF Materia Medica Holding." The papers promoting the benefits of RADs are authored by a variety of Russian authors, but they are nearly all co-authored by or associated with one person, Oleg Epstein, who is also the company's founder.

Epstein and his Russian compatriots have been very clever about disguising the fact that their "release-active drugs" aren't drugs at all. Their papers are full of scientific jargon, which has no doubt helped them get their work past reviewers who (as every scientist who has published papers knows) can sometimes be a bit lazy.

They've also taken advantage of–one might say abused–the U.S. clinical trials system, ClinicalTrials.gov, by registering 22 studies of RADs there, such as this one.

The authors of the BMJ report (Alexander Panchin, Nikita Khromov-Borisov, and Evgenia Dueva, all Russian, though Dueva is based in Canada) are unsparingly blunt in revealing how Epstein has manipulated the scientific system in Russia to gain approval (and lucrative sales) of his so-called drugs. For example, Epstein has published 90 papers on RADs in a single journal, including 48 in a special issue that he edited himself.

Panchin and colleagues also took a closer look at 6 papers about RADs that were published in English-language journals, all co-authored by Epstein. They report that
"the articles contained misleading descriptions of active substance concentrations, severe flaws in study design and methodology, as well as concealed conflict of interests.... the authors did not mention that MMH manufactures and sells RADs and holds the corresponding patents. Epstein was not mentioned as the founder and CEO of MMH."
They contacted all of these journals, and only one journal, PLoS ONE, went so far as to retract the bogus science on RADs. Kudos to PLoS ONE for doing so. The other journals, some of them published by reputable scientific publishers including Elsevier, Wiley, and Springer, either didn't respond or refused to take action.

Fortunately for consumers, RADs haven't yet spread into U.S. and European markets, although their manufacturers are trying. In a recent letter published in a the Journal of Medical Virology, Epstein and his co-authors write that
"Currently we are in the process of approving evaluation requirements for our products, taking into account their peculiarities and allowing their potential authorization in the USA and Europe."
Buyer beware. The Russian quacks are coming.