Peer review post-mortem: how a flawed aging study was published in Nature

"This has resulted in a fierce battle between different schools of thought. In one corner: demographer Jim Vaupel of Germany’s Max Planck Institute for Demographics. In the other: Jay Olshansky. “Propaganda”, was Vaupel’s verdict on the day that Evidence for a limit to human lifespan was published. “It all tells a very compelling story”, Jay Olshansky told the New York Times."

Welcome to scientific publishing. The only thing surprising here is "Demographic Day". How do you celebrate that?

By the way, here is the graphs from their previous article showing the basic problem:

https://images.nrc.nl/h5Sc3JoCu9fK3H1T4I3qWvfeDOU=/1920x/sma...

Very nice investigation. The conclusion is golden:

Retract the article? If, as in this case, there is no question of scientific malpractice, that would be highly unusual. However, one or two critical responses may be added to Jan Vijg’s article. One such response is currently under peer review.

“I hope Nature accepts one of them,” says Vijg on the phone. Because then he’ll get to write a response. “And we’ll have another article in Nature.”

This seems like a tempest in a teacup, and a distraction from things that actually matter.

No-one in the scientific community, and certainly none of the people mentioned in the article, thinks that there is a limit to life span that cannot be overcome or changed through medical science. Olshansky is one of the principals of the Longevity Dividend initiative, for example, a group of researchers who want to slow aging and increase funding to the NIH for that goal. Vijg is on record a number of times over the years talking about slowing the aging process, and has collaborated with the SENS Research Foundation. Vaupel has long worked to popularize the concept of plasticity of aging in response to environment and medicine.

Aging is caused by a few distinct processes that are independent in the sense that removing one won't remove any of the others, and linked in the sense that each of them tends to speed up and make worse the consequences of the others. See the SENS outline or the Hallmarks of Aging paper for examples of categorization. It is perfectly possible for there to exist in these processes one that produces a very high rate of mortality at later age (100+) when it goes unaddressed. A very high rate of mortality looks a lot like a limit.

A good candidate for this process is the accumulation of transthyretin amyloid. This appears linked with mortality due to heart disease in younger old people (70-100), but only in 10% of cases based on analysis to date. Yet in supercentenarians, those 110 or older, transthyretin amyloidosis is the primary cause of death, based on the small number of autopsies carried out by those capable of such analysis. No presently available form of medicine does anything to reduce levels of this amyloid, and nor is there any presently available therapy that even aims at that goal.

However, there is a company, Pentraxin Therapeutics, that has a therapy capable of clearing this form of amyloid, somewhere in the glacial processes of Big Pharma development. Promising trial results were reported in 2015.

All aspects of aging are potentially modifiable and controllable, in the same way as any chronic disease state is given the technology to do it. That has absolutely nothing to do with present day demographics and whether or not we can talk about limits due to present mechanisms operating to produce aging. But I do think it is far more important than understanding the precise details of how aging arises and how mortality rates can be decomposed and assigned to specific components of aging.

Interesting writeup. We saw this coming on Publons: https://publons.com/p/518732/

>There is no clock in our bodies.

Circadian rhythms? Telomeres shortening?

Sex sells, even in the scientific community. But I find studies based only on demographic calculations silly without some kind of reason why the data is the way it appears to be. If there is a limit what causes it? If there is no limit how can we know that? That there is a lady in Italy who just turned 117 is interesting but not meaningful to the question of lifespan.