Would a fast metabolism make you age faster?

[Contemplation]

There was a study before that concluded that a low calorie diet increased life span because it reduced the metabolic rate of the individuals.

Another reason why a fast metabolism might make someone age faster, is because oxidizing fats releases free radicals. If you have a higher metabolic rate you’re probably making more free radicals and at a faster rate than a lean person would.

I notice that creatures with slow metabolisms live long for their body size. These creatures included turtles, tortoises, and mole rats.

[Surreal]

According to the Mitochondrial Free Radical Theory of Aging (MFRTA) a higher Basal Metabolic Rate (BMR) should be associated with increased mortality. Some human studies do show an inverse relationship between BMR and longevity, but these studies are plagued with confounders (obesity, smoking, drinking, and inflammation all elevate BMR):

High Basal Metabolic Rate Is a Risk Factor for Mortality: The Baltimore...

I wouldn’t put too much credence in the MFRTA due to the lack of empirical support (e.g. antioxidant supplements do not reduce mortality and some species like rockfish, lobsters, and naked mole rats don’t seem to show any signs of aging at all). More recent research indicates that aging isn’t mainly result of wear and tear on our bodies but that it appears to be programmed into our DNA.

[yabob]

@Surreal

…

I wouldn’t put too much credence in the MFRTA due to the lack of empirical support (e.g. antioxidant supplements do not reduce mortality and some species like rockfish, lobsters, and naked mole rats don’t seem to show any signs of aging at all). More recent research indicates that aging isn’t mainly result of wear and tear on our bodies but that it appears to be programmed into our DNA.

On the other side, one species that ages faster than it “should” is the Virginia Opossum which has an unusually short lifespan for its size and metabolic rate. They generally live about 1-2 years in the wild, and if well cared for in captivity are very lucky to make 4.

[Atamasama]

But they’re possums, maybe that’s just how long it takes for them to get really good at faking it.

[Broomstick]

I’d also like to point out that birds have very high metabolic rates yet live a long time for their size/BMR.

So, even if there is some relationship between BMR and aging there a bunch of other stuff going on that also affects aging and metabolism.

[RivkahChaya]

Another data point, the implication of which, I have no idea, is that the smaller a dog’s breed is, the longer it tends to live. Chihuahuas often make it to 18, while Great Danes live to be only 9 or 10 (which is a huge cosmic joke, if you ask me), but smaller dogs eat more of a percentage of their weight than larger dogs, so I presume that means the little ones have a higher metabolism. They also move more, although a lot of that has to do with trying to keep up their body heat, which is not a problem for bigger dogs.

[Darren_Garrison]

Tangental, but primates have a lower metabolism than would be expected for mammals their size. (I ran across this study a few days ago and thought it was new, but googling it up again shows it happened several years ago.)

[DSeid]

We had a good thread here a bit back about differing animal life spans (my small contribution), and bottom line is that Broomstick seems to be spot on. There does seem to be a relationship between metabolic rate and aging, but across species at least it is not the sole factor.
If so the key player may be mTOR pathways. Maybe oxidative stress is part of that, but only one part.

…In recent years, much effort has been applied to defining the mechanisms by which inhibition of mTORC1 enhances longevity. Not surprisingly, the picture that has emerged is complex. Multiple mTORC1-regulated processes seem to contribute to the pro-longevity effects of mTORC1 inhibition in a coordinated and overlapping manner. …

It impacts mRNA translation.

a common theme of enhanced translation efficiency of metabolic and stress genes in response to mTORC1 inhibition has emerged.

It impacts autophagy.

Activation of autophagy by inhibition of mTORC1 presumably maintains cellular function during ageing by allowing enhanced degradation of aged cellular components

It impacts stress and resistance against threats from "other’ (xenobiotic threats).

It impacts mitochondrial function.

The best evidence for a direct mitochondrial role in longevity downstream of mTOR signalling comes from yeast, in which inhibition of mTORC1 results in a metabolic shift towards greater mitochondrial respiration, thereby increasing chronological lifespan

It impacts inflammation.

a reduction in chronic, age-associated inflammation is another attractive mechanism by which mTORC1 inhibition could slow multiple age-related pathologies in mammals.

It impacts the decline in stem cell function.

In mammals, a decline in stem-cell function is likely to be an important cause of age-related pathology67. There is increasing evidence that mTORC1 has a central role in this process, and that inhibition of mTORC1 can preserve, and perhaps even rejuvenate, stem-cell function in a variety of tissues.

My impression remains that the most effective way for an individual to impact these pathways in themselves continues to be regular exercise and good nutrition, rather than even metformin (as one relatively benign drug being studied that impacts these pathways) or the level of calorie restriction that the op refers to (likely meaning this recent one)

[DSeid]

I’ve tried to think of another way to address the op by thinking about what actually speeds up metabolism. The one I came up with higher than normal thyroid hormone levels (hyperthyroidism). Thyroid hormones are a basic regulator of metabolism overall.

Quick search.

Chronic hyperthyroidism in rats leads to shortened lifspans by way of “acceleration of aging during the young or middle-aged period.”

A bit more going the other way.

One should emphasize that the most striking findings concerning potential contribution of TSH and thyroid hormones to lifespan regulation, were obtained in the studies performed on centenarians (and almost centenarians). In 2009, Atzmon et al. [7] published the results of studies on thyroid disease-free population of Ashkenazi Jews, characterized by exceptional longevity (centenarians). They have observed higher serum TSH level in these subjects as compared to the control group consisted of younger unrelated Ashkenazi Jews, as well as to another control group obtained from The National Health and Nutrition Examination Survey (NHANES) program of studies [7]. Therefore, these findings appear to support previous observations, indicating that serum TSH shifts progressively to higher levels with age (e.g., [36]). Moreover, the authors have observed an inverse correlation between FT4 and TSH levels in centenarians and Ashkenazi controls, and finally, they have distinctly concluded that increased serum TSH is associated with extreme longevity [7] … may suggest a potential role of decreased thyroid function in lifespan regulation, leading to remarkable longevity. Such a hypothesis seems to have been confirmed by the findings obtained in the Leiden Longevity Study, demonstrating the associations between low thyroid activity and exceptional familial longevity [38].

In turn, Corsonello et al. [39] have demonstrated that age is associated with a decrease in free triiodothyronine (FT3) and FT4 but not with increased TSH levels. Moreover, children and nieces/nephews of centenarians had lower FT3, FT4 and TSH levels as compared to the age-matched subjects [39]. It may, at least partially, confirm an important role of low thyroid function in the regulation of lifespan.

[Surreal]

@DSeid

I’ve tried to think of another way to address the op by thinking about what actually speeds up metabolism.

Um, how about exercise? Or having greater muscle mass?

You have to look at the disconfirming hypotheses as well.

[DSeid]

The impact of exercise on resting and more so overall, (inclusive of non-exercise activity) metabolism is, to my read, pretty unclear. Here we need to focus on total energy expenditure (TEE) I think.

The direct effects of exercise on metabolic rate are pretty small as part of total daily expenditure.

Increased muscle mass actually also has fairly little impact on RMR. Muscle at rest actually does not burn so much, maybe 6 Cal/pound/day according to most sources. Adding 10 pounds of muscle is a pretty big deal but only increases RMR by 60 Cal/d. Compared to other portions of lean body mass, like organs, its a piker. A tiny portion of TEE.

There is EPOC, the after burn, the recovery short term increase. But then there is the increased cardiorespiratory fitness that leads to a lowered resting heart rate and increased efficiency in movement during the day that occurs with fitness. Lots of studies out there many conflicting with each other. For example:

There exists considerable controversy regarding the impact of different modes of exercise training on total daily energy expenditure (TEE). To examine this question, young, nonobese women were randomly assigned to a supervised 6-month program of endurance training, resistance training, or control condition. TEE was measured before and 10 d after a 6-month exercise program was completed … TEE did not significantly change when measured subsequent to the endurance or resistance training programs

I don’t think we can say with confidence that exercise, even resistance exercise, speeds up metabolism overall.

And the impact on mTOR seems to vary by exercise and by tissue. I do not claim to understand its complexities. I readily admit that my impression that exercise and nutrition may hit mTOR the right ways for the right tissues has, so far, little hard science that I at least can parse together to support it.

[Broomstick]

Getting back to mitochondria and free radicals…

There may be a link between evolutionary pressure to evolve highly efficient mitochondria and lifespan. If you’re only going to live a year or two then who cares if you have sloppy mitochondria that leave a mess about the cell? If you’re more likely to be eaten by a predator or become roadkill then what does it matter that you’re aging fast? Reproduce fast as hell, leave a bunch of babies, and you’ve still won in a Darwinian sense.

But… if you could live longer, if your can potentially escape predators… then those who live longest might well leave the most descendants. In which case you now have pressure to evolve highly efficient mitrochondria that don’t leave a mess of free radicals while generating ATP.

Or… if your lifestyle requires a LOT of energy then evolving highly efficient mitochondria means more efficient energy production and use. Which, as a side effect, might mean less damage from free radicals, less internal wear and tear on the cells, slower aging, and a longer life as a side effect of more efficient energy production and use.

There is a correlation between relatively long-lived critters and mitochondrial efficiency. There are birds - flight enables most birds to evade predators, meaning that there is the potential to evade being eating by something else through multiple breeding seasons. Also, flight requires a LOT of energy. Birds have pressure to evolve efficient mitrochondria to provide the energy required for flight, and flight means evading predators longer in at least some cases, so birds have not one but two incentives to evolve better mitochrondia and … surprise! Birds also tend to be long-lived, especially for something so small and with such a high metabolism.

Another critter with high energy needs is… US! Yes, us - our brains are enormous metabolic gas guzzlers, on top of the primate optical system being fairly energy intensive as well. Not only are primates in general relatively long-lived, but we’re also the longest-living primates. So we have that “incentive” for better mitochondria. On top of that, we not only are pretty good at evading predators, we’ve hunted most of what used to eat us either to extinction or darned close to it so we have ample time to reproduce. Another double-whammy.

Look at elephants - not much takes on an adult elephant, so they don’t have to be in a hurry to reproduce and can have a long breeding lifetime. And… elephants live a long time. So do whales - again, not much takes on a grown whale, they aren’t a hurry to reproduce… and they live a long time.

Then there are island populations of animals that are longer-lived than their mainland counterparts - lack of predators means animals that might otherwise only breed once can breed again if only they lived long enough… and those that do leave more descendants. If I recall, there is actually a species of opossum that fits that description. It would be interesting to know if that species has more efficient mitochondria than the other opossums do, wouldn’t it?

The thing is, there are multiple reasons that a species could evolve better mitochondria that produce fewer free radicals while synthesizing ATP, which makes the whole “what does metabolism have to do with lifespan?” question more complicated. As I noted, a long life might be a side effect of something else that is pushing for efficiency energy production/use. Or it could be that lack of predation shifts the pressure off reproducing early and often to a strategy involving more time to reproduce. Critters with “sloppy” mitochondria with a slower metabolism can live longer, too.

In other words - it’s all more complicated and interconnected than it first appears. And that’s just considering mitochondria… as others have noted there are other factors impacting longevity at work, from mTOR to thyroid hormones to probably a bunch of other stuff.

There’s no magic bullet and no one answer.

[Contemplation]

Would a high metabolism caused by heat generation shorten someone’s life?
Let’s say someone lives someplace cold so they have to shiver every day. Both shivering and brown fat burn a lot of calories.
Would this make someone die sooner?

[DSeid]

I wouldn’t think so. My speculation is that it matters what tissue is having mTOR impacted (or otherwise revving). Brown fat revving along, even some shivering, probably not. But I have no real support for that being my thought. Best I got is this: mice with hyperactive brown fat (Pten +) live longer. And that aint much.