International Business Department           Liu Bojia           January 10, 2023

  Aging is an unavoidable experience for everyone, and most of what we understand by aging on a daily basis may come from images we see in our lives, such as wrinkles on the face and a grey hair or two. But from a scientific point of view, aging involves complex changes in internal physiological processes. In recent years, a concept called "Interorgan Communication in Aging" has emerged.

  According to this theory, the transmission of information between organs and tissues becomes disrupted with age, which leads to a deterioration of physiological functions associated with aging, a change that is closely related to the lifespan of an individual. For mammals, the hypothalamus is central to the control of ageing, with its ability to regulate the production of many hormones via the pituitary gland, as well as the ability to remotely control peripheral organs by the autonomic nervous system, both of which are key to influencing inter-organ communication.

  Recently, researchers at the University of Washington identified a special class of neurons in the hypothalamus that build an information feedback loop between the brain and the body's white adipose tissue, thereby regulating the metabolism and energy release of the adipose tissue. The authors confirmed that an active exchange of information between these two parts of the body extends the healthy lifespan of mice and slows down aging.

  According to the paper, which has been published in Cell Metabolism, these neurons are located in the dorsal medial hypothalamus and are able to produce the key protein Ppp1r17. when the protein enters the nucleus of neuronal cells, it activates neurons and the sympathetic nervous system, facilitating the fight-and-flight response in individuals.

  And in the chain of events of such responses, the researchers found that white adipose tissue being activated is also an important part of the equation; when the Ppp1r17 neurons in the dorsomedial hypothalamus send signals to the adipose tissue, the latter's activity is heightened, which then releases fatty acids into the surrounding bloodstream, which act as an instant fuel for the body's movements. At the same time, the adipose tissue releases a special enzyme, eNAMPT, which travel with the circulatory system to the brain, boosting the synthesis of nicotinamide adenine dinucleotide (NAD) in the hypothalamus and elevating hypothalamic function. Such a feedback loop constitutes brain-adipose tissue information communication.

  In the mouse experiments, if the researchers specifically knocked out the Ppp1r17 protein in the dorsal medial hypothalamic neurons, the mice's adipose tissue metabolism would change, the white adipose tissue decomposition would slow down, and the mice would have a bigger fat accumulation block in their bodies. In addition, the knockout mice would have significantly elevated food intake during rest periods and would be largely inactive during active periods, with a consequent increase in body weight.

  In fact, this artificial experimental intervention mimics the phenomenon of aging, in which the Ppp1r17 protein leaves the nucleus of the cell as the individual ages, and signals from the hypothalamus to the adipose tissue are weakened, leading to slower lipolysis and a greater likelihood that the individual will become obese, with the subsequent negative effects that follow.

  And when the researchers managed to retain Ppp1r17 in the nucleus of dorsal medial hypothalamic neurons of the older mice, the mice behaved more actively, and such a simple change allowed the experimental mice to participate more actively in rollerblading compared to the older mice in the control group, and they also looked younger and did not have the obese physique that comes with the accumulation of fat at an older age. And the mice also lived longer than the control group, by an average of 6-7 per cent. With the average human lifespan of 75 years, a 7 per cent life extension is about five years, the study noted.

  In addition to this manipulation of neurons in the hypothalamus, the authors also found that supplementation with eNAMPT may be a simpler way to fight aging. Supplementation with eNAMPT is equivalent to bridging the gap of insufficient hypothalamic signals in aging and reactivating the direct brain-fat information exchange, and they have confirmed that this approach extends the lifespan of mice, which may be a potential new means of fighting aging in the future.