How can people who can’t exercise get the same neuroprotective benefits as physical exercise?

2022-06-14 0 By

Photo source:Pixabay It’s well known that exercise has many benefits for the aging brain,And the Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell at UCSFA previously little-studied liver protein may be responsible for the effect, according to new mouse studies by scientists at The University of California, Berkeley.The findings could lead to new treatments that could give people who are physically unable to exercise the same neuroprotective benefits as exercise.Exercise is the most studied and effective way to protect the brain from age-related cognitive decline.Exercise has been shown to improve cognition in people with neurodegenerative diseases such as Alzheimer’s and frontotemporal dementia, and even in people with rare genetic variants that inevitably lead to dementia.However, many older people cannot exercise regularly because of physical limitations or disabilities.Researchers have long sought therapies that would give the same neurological benefits to people with limited physical activity.The study, published in the journal Science, suggests that after exercising mice, their livers secrete a protein called Gpld1 in their blood.Blood levels of these proteins corresponded to improved cognitive function in older mice.And a study in collaboration with the UCSF Memory and Aging Center found elevated levels of the enzyme in the blood of older adults who exercised regularly.But simply increasing the level of Gpld1 produced by the mice’s livers provided the same benefits to the brain as long-term exercise, the researchers said.”If there was a drug that had the same effect as exercise, everyone would take it.Now, our research suggests that at least some of these benefits may one day be realized by taking drugs.”Saul Villeda, Ph.D., senior author of the study and assistant professor in the Department of Anatomy and the Department of Physical Therapy and Rehabilitation Sciences at UCSF.Previous studies have shown that biological factors present in the blood of young mice can rejuvenate the brains of aging mice, and that, in turn, biological factors in the blood of aging mice can cause premature age-related cognitive decline in young mice.These results intrigued Alana Horowitz, a graduate student in the lab, and Xuelai Fan, a postdoctoral fellow, who looked for possible blood-borne agents that could produce the same benefits as exercise, rejuvenating the aging brain in the same way as in the “Young Blood” experiment.Horowitz and Fan had older mice exercise regularly for seven weeks, then took blood from them and injected it into older mice that didn’t exercise at all.They found that the four-week treatment significantly improved learning and memory in older mice, similar to what was seen in mice that exercised regularly.When they examined the animals’ brains, they found evidence of a surge in the production of new neurons in the hippocampus, which had previously been shown to be rejuvenated by exercise.Horowitz, Fan, and colleagues examined the levels of different soluble proteins in the blood of exercise and nonexercise mice to find out which specific biological factors were behind this phenomenon.The team identified 30 candidate proteins, 19 of which, to their surprise, came primarily from the liver, and many have previously been associated with controlling the body’s metabolic functions.Two of these proteins are particularly important in metabolic processes, namely Gpld1 and Pon1.The researchers chose to delve deeper into Gpld1 because few previous studies had explored its function.”We thought if someone had studied the protein thoroughly earlier, maybe they would have encountered this phenomenon.””I would say that if you’re ready to take a risk and explore something new, you might find something amazing!” Villeda said.The team found that Gpld1 increased in blood circulation in the exercise mice, and that levels were associated with improved cognitive performance.An analysis of human data collected by the UCSF Memory and Aging Center’s Hillblom Aging Network research project showed that healthy, active older adults also had higher levels of Gpld1 in their blood compared to those who were less active.To test whether Gpld1 itself would drive the observed benefits, the researchers used genetic engineering to induce excessive production of Gpld1 in the livers of elderly mice, and then measured the animals’ performance through multiple cognitive and memory tests.To their surprise, the three-week treatment produced similar results to those after six weeks of regular exercise, with a significant increase in the growth of new neurons in the hippocampus.”To be honest, I didn’t expect to succeed in finding that a single molecule would give the brain as many benefits as exercise.”It seems more likely that exercise has many small, subtle effects that add up to huge benefits that are hard to isolate.””When I saw the data, I was absolutely stunned,” Villeda said.”With this protein, the liver responds to physical activity by telling the aging brain to stay young and active.””This is an important example of liver-brain communication,” Villeda added. “To our knowledge, no one knew this interaction existed before.It also made me wonder what else we’re missing in neuroscience, because we’ve largely overlooked the huge impact that other organs can have on the brain, and vice versa.”Further tests showed that Gpld1 produced by the liver did not cross the so-called blood-brain barrier, which protects the brain from toxic or infectious substances in the blood.However, the protein may affect the brain by reducing inflammation throughout the body and blood clotting, among other things.Blood clotting and inflammation are known to increase with age and are associated with dementia and age-related cognitive decline.Research is now under way in the lab to better understand how Gpld1 interacts with other biochemical signaling systems to boost brain function, with the hope of identifying specific targets suitable for treatment that could one day bring the same protective benefits to the aging brain as exercise.This article is from: China Digital Science and Technology Museum