Three anti-aging approaches appear ineffective

[corybroo]

Three approaches with a reputation for slowing aging processes proven largely ineffective

The grim news:  Intermittent fasting, mTOR targeting by rapamycin, and interfering with the release of growth hormone do not work.

Rather interesting was the way they determined this. 

 

For the assessment in mice, the scientists developed a new answer to the question of how to measure aging. "Many researchers in recent decades have used lifespan as an indirect measure of aging," explains Dan Ehninger, who is a senior scientist at DZNE. So, for example, how old do mice get—and how can that lifespan be extended?

"It is often assumed that if they just live longer, they will also age more slowly. But the problem is that mice, like many other organisms, do not die from general old age, but from very specific diseases," says Ehninger. For example, up to 90% of mice die from tumors that form in their bodies at an advanced age. "So, if you were to look at the whole genome for factors that make mice become long-lived, you would like find many genes that suppress tumor development—and not necessarily genes that play a general role in aging."

For their study, the scientists therefore chose an approach that does not emphasize lifespan, but rather focused on a comprehensive investigation of age-related changes in a wide range of bodily functions. "You can think of it as a complete health status survey," says Martin Hrabě de Angelis.

That's exactly the approach the researchers applied to the animals subjected to one of the three treatment approaches that supposedly slow aging. Across different life stages, they were analyzed and compared: How much does each parameter typically change at a given stage of life? And, do parameters change more slowly when the mice are given one of the three treatments? This study design makes it possible to determine precisely whether the natural aging process can be slowed, and with it the deterioration of important physiological functions.

The results were unambiguous. Although the researchers were able to identify individual cases in which old mice looked younger than they actually were it was clear that "this effect was not due to slowing down aging, but rather due to age-independent factors," says Dan Ehninger. "The fact that a treatment already has its effect in young mice—prior to the appearance of age-dependent change in health measures—proves that these are compensatory, general health-promoting effects, not a targeting of aging mechanisms."

[Guest]

Gosh, they are really overselling their analysis... here is the original publication:

https://www.nature.com/articles/s41467-022-34515-y

 

The authors DO have some valid points - points which are well known among researchers, but probably not sufficiently communicated to the lay public; e.g. lab mice are dying predominantly of cancer. Many human causes of death don't have a real equivalent as a source of mortality in lab mice, e.g. dementia, frailty related accidents, even most forms of CVD. Therefore lifespan studies in mice are "useless" and lifespan should not be considered when talking about aging - according to the views of the authors. They even go as far to suggest the same for humans (i.e. lifespan and aging are only loosely connected - hence lifespan should be of no concern for the public).

Specifically what they are doing is assembling an array of biomarkers for aging to compare if mice receiving crypto-CR or Rapa are looking younger on those markers than their control-peers without intervention. A sizable share of their biomarkers are indeed favorable; but they dismiss this, as part of those are somewhat changing in young mice already, not just in old mice. Their conclusion: CR, Rapa - it's all wrong! Nothing works! Not even in mice!

 

There are a couple of possible objections to their approach and conclusion:

 

1. I believe many researchers would disagree, that there is no or only a loose connection between aging and lifespan. Biologically and semantically. Yes, there can be very specific causes of mortality. And they can kill people unrelated to if they age fast or slow. See the black death in medieval Europe. But we have the "hallmarks of aging" or the SENS-strands of "damage" and repair. This is what nowadays kills the vast majority of people even in the country of India or the country of Africa (/s). Cancer definitely is mostly age-related and part of the hallmarks of aging. So it's disingenuous to just dismiss delay and lower mortality of cancer in mice as not relevant for aging, just because it happens to be the major cause of death.

CR and Rapa make mice life longer, because the counteract aging. In mice it's a specific aspect of the hallmarks of aging, that is particular to mice - cancer. But that still is aging. And they live longer because of that.

 

2. CR and Rapa are working in flies, worms and single celled organisms, too. I'm not so sure, but I wager yeast cells or c.elegans don't die of cancer. And they are functionally "younger" at their specific age - even if this might not be observed by the biomarkers of the authors. So there is certainly more to it. See it this way: if organisms behave like younger versions of themselves in terms of physical and "social" activity. And they live longer. It seems odd to use a definition of "aging" that would say that these organisms did not defy aging.

 

3. A central argument to dismiss data that they don't like, seems to be that changes are already observed in young mice - who supposedly don't have aging that needs fixing. This is again an odd argument: they seem to imply (but not state explicitly), that CRON or Rapa work by reversing aging. Not by delaying it. Of course biomarkers can be changed favorably even in young, if they delay the accumulation of "damage". That's why people do blood tests etc. to see if they need to take a drug or lifestyle change for prevention. The result will a change in their biomarkers (e.g. inflammation markers, APOB, Kidney-parameters etc.). That is not a contradiction to an anti-aging effect of an intervention.

 

Now I personally am skeptical if CRON or Rapa (as done by advocates in the human aging field) are working humans to the same extend as they do in mice. But this paper is building up 2 straw man (point 1 and 3) and declares victory after burning them to the ground. It's just that probably most researches in the field would have a problem with their explicit and implicit assumptions.

 

I still give the paper a 5 out of 10 largely for their process.

 

 

 

 

 

 

[Saul]

Well said.

  --  Saul