Researchers here make an interesting discovery in rats, finding an age-related change in the structure of specific neurons that encourages greater intake of calories and dysfunctional metabolism by suppressing satiation feedback. In rats this mechanism can be manipulated by diet and genetics to alter the pace at which older rats become overweight and metabolically abnormal. As is often the case in research, this discovery is a proximate cause to the problem of metabolic regulation, and it is entirely unclear as to how the deeper mechanisms of aging, such as chronic inflammation, mitochondrial dysfunction, and so forth, are causing it or otherwise relate to it.
As we get older, we become more prone to being overweight and obesity. Obese people are more susceptible to diabetes, hyperlipidemia, and other chronic diseases. Previous studies have suggested that middle-age weight gain is caused by a decline in overall metabolism due to aging, but the mechanism was unclear. A protein called melanocortin-4 receptor (MC4R) detects overnutrition and regulates metabolism and appetite to prevent obesity. MC4Rs stimulate metabolism and suppress food intake in response to an overeating signal from melanocortin.
Initially, a research team examined the distribution of MC4Rs in the rat brain by utilizing an antibody they had developed specifically to make MC4Rs visible. They found that MC4Rs are present exclusively in primary cilia of specific groups of hypothalamic neurons. The team next investigated the length of the primary cilia that had MC4Rs (MC4R+ cilia) in the brains of 9-week-old (young) rats and 6-month-old (middle-age) rats. The team found that MC4R+ cilia in middle-aged rats were significantly shorter than those in young rats. Accordingly, the metabolism and the fat-burning capacity of middle-aged rats were much lower than those of young rats.
The team next analyzed MC4R+ cilia in rats under different dietary conditions. The results showed that MC4R+ cilia in rats on a normal diet gradually shortened with age. On the other hand, MC4R+ cilia in rats on a high-fat diet shortened at a faster pace, while those in rats on a restricted diet shortened at a slower pace. Interestingly, the team also found that MC4R+ cilia that once disappeared with age were regenerated in rats raised under two months of dietary restriction. In the study, the team also used genetic technologies (knockdown of CILK1) to make MC4R+ cilia shorter in young rats. These rats showed increased food intake and decreased metabolism, leading to weight gain.
Link: https://www.eurekale...eleases/1037463
View the full article at FightAging
