I thought it was a pretty uncontroversial statement, but OK. Mice in the wild are subject to heavy predation. Predation and a variety of accidents is the #1 cause of death for mice by a wide margin in their natural environment, whereas for humans that’s pretty far down the list. Which means that a lab is going to be far more protective for a mouse than a human. Humans “in the wild” had it pretty rough, as Hobbes put it, lives that were nasty, brutish and (ahem!) short. Which is what a mouse has in the wild. But humans developed civilization (something mice should try!) and today, at least in developed countries, our environment is not far away in safety and convenience than what you can get in a lab, so you are not getting much of a jump in longevity transferring a human to a lab compared to a mouse to a lab. There are countless advantages to a modern human environment, note the massive jump in longevity achieved by the introduction of convenient hygiene and sewage/plumbing. The hygiene arrangements for mice in the wild are deplorable. We can complain about the healthcare system, especially in the USA, but look at what wild mice get - if a mouse falls sick, becomes frail and cannot run as fast, the first healthcare intervention is from Dr. Owl, whose patients, spoiler alert, inconveniently always end up dead on the operating table. The necessity to engage in risky foraging for food, with no assurance of consistency or quality is something mice face daily, whereas the days of humans fighting off lions and hyenas for scraps has been abolished by civilization. A lab is a huge boon in this respect for wild mice compared to humans who in their environment have access to nutrition with little risk and effort.
But the dead giveaway of the vast chasm between wild and lab for a mouse vs human in his civilized environment and a lab is one simple fact: mice almost never reach advanced old age in the wild, whereas they regularly do so in a lab. The moment a mouse falters whether by illness or first whiff of age-related disability, they cannot survive in the highly competitive and hostile environment. So they almost never get the chance to be old and frail and putter along. A lab, is a godsend and paradise in comparison. Humans by contrast, by their majorities reach old age and many very advanced old age right in their civilized environment of developed countries. Mice have much more to gain by being in a lab than a human would - like in at least reaching old age; humans reach old age, and extreme old age just fine outside a lab.
And how do we know that our developed world enviroment is almost as good as a lab for a human? Because we see that by the evidence in animals. A feral cat in an urban environment lives longer on average than in the wild as their food supply is often supplemented by humans and they are less subject to predation, but yet, an urban feral cat lives on average only about 6 years or so. Meanwhile the same species of cat, in the human environment as a pet, with protection, access to quality food and vet care, live 15 years, or more than twice as long, and regularly even 20+. They share our environment, our homes, and they max out their lifespans - they don’t gain much if anything in lifespan from being put in labs, and we have those stats. It’s not like cats break longevity records in labs the way mice do. Our human environment in developed countries is pretty optimized for human lifespan, because that’s what civilization has focused on for thousands of years - prolonging life, minimizing risk, upping the quality and convenience. A feral cat - 6 years, a cat pet in human environment 15-20, or a boost of 200%-400%. Putting a human in a lab is not going to give us a 200%-400% boost in longevity, because our civilized environment is already pretty human adapted. Which is why my uncontroversial statement was that mice have vastly more to gain from a lab than a human. We die in old age, often extreme age, wild animals rarely do.
Wrt. microbes. No doubt there is microbe related morbidity and mortality. But my contention is that microbes are not the primary driver of the rate of aging. If you eliminated all microbes, humans would not suddenly age more slowly. Look at that chart posted by RapAdmin a few posts up - Hallmarks of Aging. How many of those do you think are affected to any great degree by microbes? Dysbiosis - OK… which incidentally is a consequence of aging not as much a cause of aging as immune senescence makes us vulnerable to disbiosis. Otherwise it’s hard to see where in these hallmarks of aging microbes have any substantive role: stem cell exhaustion, genomic instability, loss of proteostasis, telomere attrition, altered intercellular communication, disabled macroautophagy, mitochondrial dysfunction, cellular senescence, chronic inflammation. We started this discussion over whether lifestyle interventions that you outlined can slow the rate of aging to give us 130-150 lifespans. I don’t think microbes measurably affect the rate of aging. Healthspan - sure. Lifespan - I can’t see it.
Look, it’s clear you have a passionate belief in your model of aging where lifestyle measures have a central role in affecting the very rate of basic aging in humans and can potentially give us a very substantial lifespan boost on the level of 130-150 years. I have a different view of how aging works, and believe that the role of lifestyle interventions is limited to healthspan and fulfilling what really limits us, our genetic blueprint and therefore that limit cannot be impacted and extended by lifestyle interventions alone.
That’s our fundamental disagreement. We do agree on pharma! I think we’ve presented our views as clearly as we could, and unless new facts and arguments emerge, our positions are pretty set. I propose that we leave it here until there are further developments, perhaps amazing new studies or whatnot.
Thank you for your vigorous presentation - peace!
