Longevity Briefs: Is Metabolic Rate The Key To Exceptional Longevity?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Even when not exercising, we must spend a certain amount of energy simply to ‘idle’. Depending on how much exercise we do, this can be as much as 70% of daily energy expenditure, and is known as the resting metabolic rate, or RMR. While there are some notable exceptions, species with lower RMR tend to live longer after controlling for body weight. One possible explanation for this is that higher RMR means faster molecular wear-and-tear as a result of factors like reactive oxygen species (ROS) – harmful byproducts of metabolic processes that damage proteins and DNA.

One example of a long-lived species with low RMR is the naked mole-rat. Despite having the guinea pig as one of its closest evolutionary relatives, naked mole-rats can live for over 30 years in captivity. What’s more, naked mole-rats show very few signs of age-related disability until they are about to die – a quality known as negligible senescence. For these reasons, scientists are interested in studying what makes these rodents so special. In this study, researchers note another interesting property of naked mole-rat metabolism: unlike most species, their RMR does not appear to change much with age.

The discovery:

Researchers measured the body weight and RMR of 76 captive naked mole-rats from five different colonies. Naked mole-rats live in large underground communities with non-breeding workers and a single queen. The mole-rats studied here included both breeders and non-breeders, and ranged from 8 months to 15 years of age, roughly corresponding to young adult to late middle age in terms of ‘human years’.

Each animal was placed alone in a sealed chamber so that its oxygen use and carbon dioxide production could be recorded. This was then used to calculate RMR. Researchers found that heavier animals had higher RMR, which is to be expected as larger animals have more tissues to support and therefore consume more energy. After controlling for body weight, queens had slightly higher RMR, which is also unsurprising as reproduction and lactation requires a lot of additional energy. The more surprising finding was that age did not significantly influence RMR. In most species, resting metabolic rate declines with age due to the loss of muscle (which is responsible for the largest chunk of RMR). Even after controlling for body weight, factors like hormonal changes and reduced function in mitochondria (the cellular ‘power plants’ responsible for converting energy from nutrients into a form that is usable by cells) still contribute to a decline in RMR. In naked mole-rats, there was a a trend towards increased RMR, which was not statistically significant when body weight was accounted for.

Consistent with previous studies, naked mole-rats had far lower RMRs than would be expected for animals their size. Another interesting observation was that animals from colonies that had recently experienced social conflict had higher RMRs, suggesting that RMR changes in response to stress.

The implications:

What does all this mean, and can we speculate about any implications for human health? Naked mole-rats have exceptionally low RMRs relative to their size and maintain low RMRs as they age. Does this mean that humans should strive for a low RMR to delay ageing? The naked mole-rat’s low RMR is probably an evolutionary adaptation to its subterranean environment, in which it is protected from external conditions like temperature fluctuation and does not need to expend as much energy to survive. We can’t copy the naked mole-rat’s biology (yet). And while it’s not impossible that people with intrinsically lower RMR, irrespective of body weight, are ageing at a slower pace, striving for a lower metabolic rate won’t improve health in and of itself. Losing muscle while gaining fat will lower RMR while maintaining body weight, but is the opposite of desirable in terms of ageing. It would be better to focus on behaviours that have been shown to enhance those repair processes that help counteract the harmful effects of metabolism (exercise, sleep, plant-based diets rich in antioxidants and fasting/calorie restriction).

The more human-relevant finding might be the fact that RMR doesn’t seem to change much with age in naked mole-rats. This is probably an indication that the underlying biology of ageing isn’t progressing much, not necessarily that the stable metabolic rate itself is helping the species live longer, though that might be true as well. For humans, taking action that preserves resting metabolic rate in old age, such as building muscle and staying physically fit, isn’t going to be a bad idea either way.