Good article, thanks. I can tell you from my perspective frailty is a massive problem in the growing population of elderly patients. As a primary care physician, I am astounded at the number of patients I have that can barely get up out of a chair. This level of weakness increases falls, makes them vulnerable to back pain and other joint pain, and is certainly associated with cognitive decline. Unfortunately, it is very difficult to get them to take even minimal action to reverse this process by lifting weights. They get sick with life-threatening injuries and illnesses, go in the hospital, and we save them over and over again. But at each step, they are getting weaker and weaker. Lifespan-increasing, healthspan-no.
It would be nice if we could improve bone health too. I feel it would be easier to make an Ozempic for muscles than it would be to persuade most people to exercise regularly.
Yes, western life expectancy has increased by 20 years or in last century or so but the typical age old people die at hasn't changed nearly as much. Life expectancy at the age of 60 increased only by 5-10 years in last 100 years. In last 20 years life expectancy at age of 60 increased by around 2 years in most western countries. And those two years were largely spent in sickness, disability, pain and misery.
Does aging compound the way interest compounds, with each each failure making the next more likely? And if so, what stops that compounding in mole rats?
Does cancer succeed because a defecting cell no longer benefits from the body's error-correction systems? But then it's also vulnerable to its own internal errors?
Do mTOR inhibitors work not by slowing damage but by simplifying what cells need to coordinate? Switching from complex growth tasks to simpler maintenance?
Do long-lived species share not just slow metabolisms but also simpler signaling? Fewer things cells need to agree on?
I will probably end up writing an essay in response to this provocative article, but for now I wanted to share a link to this recent publication by biologist Michael Lynch: https://pnas.org/doi/full/10.1073/pnas.2414742121
His central finding is that multicellular organisms pay more than ten times the energetic cost per unit biomass compared to unicellular organisms of similar size, owing to "nonproductive features such as cell adhesion, support tissue, and intercellular communication and transport." This supports your discussion of why metabolic rate predicts lifespan.
But Lynch also finds a crucial asymmetry that your article doesn't address: within any given species, the metabolic cost of producing biomass increases with individual size as the organism grows, but across species phylogenetically, the energetic expense per unit biomass declines with increasing adult size.
This countergradient creates a genuine tension the simple "bigger animals live longer because of slower metabolisms" narrative.
This would also reframe mTOR inhibition and caloric restriction not merely as "slowing metabolism" but as reducing the rate at which coordination costs compound.
...but this framing also makes the naked mole rat's violation of Gompertz's law even more striking.
That's so interesting. So multicellular organisms are expending a lot of energy on coordinating between all the different parts of them. That makes intuitive sense.
It can't be a coincidence that the relationship between metabolic cost and the size is the same as the relationship between cancer rate and size. (Bigger species less but bigger animals within species more.)
A minor quibble, lobsters are not insects, or particularly closely related to them. They are crustaceans.
Good article, thanks. I can tell you from my perspective frailty is a massive problem in the growing population of elderly patients. As a primary care physician, I am astounded at the number of patients I have that can barely get up out of a chair. This level of weakness increases falls, makes them vulnerable to back pain and other joint pain, and is certainly associated with cognitive decline. Unfortunately, it is very difficult to get them to take even minimal action to reverse this process by lifting weights. They get sick with life-threatening injuries and illnesses, go in the hospital, and we save them over and over again. But at each step, they are getting weaker and weaker. Lifespan-increasing, healthspan-no.
It would be nice if we could improve bone health too. I feel it would be easier to make an Ozempic for muscles than it would be to persuade most people to exercise regularly.
Yes, western life expectancy has increased by 20 years or in last century or so but the typical age old people die at hasn't changed nearly as much. Life expectancy at the age of 60 increased only by 5-10 years in last 100 years. In last 20 years life expectancy at age of 60 increased by around 2 years in most western countries. And those two years were largely spent in sickness, disability, pain and misery.
Great article. Lots of questions!
Does aging compound the way interest compounds, with each each failure making the next more likely? And if so, what stops that compounding in mole rats?
Does cancer succeed because a defecting cell no longer benefits from the body's error-correction systems? But then it's also vulnerable to its own internal errors?
Do mTOR inhibitors work not by slowing damage but by simplifying what cells need to coordinate? Switching from complex growth tasks to simpler maintenance?
Do long-lived species share not just slow metabolisms but also simpler signaling? Fewer things cells need to agree on?
I will probably end up writing an essay in response to this provocative article, but for now I wanted to share a link to this recent publication by biologist Michael Lynch: https://pnas.org/doi/full/10.1073/pnas.2414742121
His central finding is that multicellular organisms pay more than ten times the energetic cost per unit biomass compared to unicellular organisms of similar size, owing to "nonproductive features such as cell adhesion, support tissue, and intercellular communication and transport." This supports your discussion of why metabolic rate predicts lifespan.
But Lynch also finds a crucial asymmetry that your article doesn't address: within any given species, the metabolic cost of producing biomass increases with individual size as the organism grows, but across species phylogenetically, the energetic expense per unit biomass declines with increasing adult size.
This countergradient creates a genuine tension the simple "bigger animals live longer because of slower metabolisms" narrative.
For me, Lynch's data suggest a third framing: aging is the rising marginal cost of maintaining multicellular coordination. https://symmetrybroken.com/the-synchronization-tax/
This would also reframe mTOR inhibition and caloric restriction not merely as "slowing metabolism" but as reducing the rate at which coordination costs compound.
...but this framing also makes the naked mole rat's violation of Gompertz's law even more striking.
That's so interesting. So multicellular organisms are expending a lot of energy on coordinating between all the different parts of them. That makes intuitive sense.
It can't be a coincidence that the relationship between metabolic cost and the size is the same as the relationship between cancer rate and size. (Bigger species less but bigger animals within species more.)
I wrote a bit more here: https://www.symmetrybroken.com/maintaining-divergence/#evolutionary-biology-the-naked-mole-rat-solution