Longevity Briefs: Is Middle-Age Spread All In The Mind?

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:

As we get older we tend to put on weight, which in turn raises our risk of age-related diseases like type II diabetes. This is generally thought to be due at least in part to a lower resting metabolic rate – the rate at which the body burns calories when not exercising. Burning fewer calories throughout the day means it’s easier to reach a calorie surplus (and therefore to gain weight) unless you reduce food intake or increase calorie expenditure accordingly through exercise. Some research has challenged this notion, suggesting that metabolic rate doesn’t actually change that much between adolescence and age 60, and that overeating might be the main culprit behind ‘middle-age spread’. It may be a bit of both, but what actually causes these disruptions in appetite and metabolism as we get older? A recent study has uncovered a potential mechanism in the brain.

The discovery:

In this study, researchers looked at structures called primary cilia in the brains of rats. Primary cilia are microscopic structures that extend from neurons in the hypothalamus. The researchers found that these primary cilia had high levels of a receptor called melanocortin-4 receptor (MC4R), which helps prevent weight gain by detecting overnutrition and regulating appetite and metabolic rate accordingly. The researchers then compared young 9 week-old rats to ‘middle aged’ 6 month old rats, and found that the MC4R-bearing primary cilia in the older rats were significantly shorter than in their younger counterparts. When they used genetic techniques to artificially shorten the primary cilia in young rats, those rats ate more, had reduced metabolic rates, reduced fat-burning ability and didn’t respond to the appetite-suppressing hormone leptin. This seems to suggest that shortened primary cilia during ageing might cause disruptions in appetite and metabolism leading to weight gain.

The researchers also discovered that diet could affect the shortening of the primary cilia. Feeding the rats a high-fat diet accelerated the pace of shortening, while cutting their calorie intake by 40% (dietary restriction) slowed it down. Intriguingly, putting the rats on dietary restriction for two months actually regrew some primary cilia that had completely disappeared with age, suggesting that the process is reversible to some extent.

The implications:

While these findings may come from rats with fairly small sample sizes in some experiments, the implications are quite exciting if similar mechanisms can be found in humans. They imply that maintaining a healthy diet and practising some dietary restriction when you are young may help preserve proper appetite and metabolic function into middle-age. They reinforce the idea that dietary restriction could be a uniquely effective intervention for obesity, with the potential to reverse some age-related changes in appetite and metabolism. There may also be ways to target MC4R with drugs to prevent or reverse age-related obesity.