A team of experts from the Dana-Farber Cancer Institute at Stanford University School of Medicine (USA) have shown that brain aging could be prevented or reversed by fixing a bug in the ‘soldiers’ (myeloid cells, actually) front-line of the body’s immune system; in short, by adjusting the immune system.
Mouse experiment
The experimental treatment turned old, weak mice into healthy animals by regenerating their aging bodies.
“The result is that the cells are basically depleted of energy. They are simply fatigued and not performing well, ”explains Andreasson. “They do not engulf. They don’t clean up the debris. ”These debris include misfolded proteins associated with neurodegeneration, the authors write.
The recovery of the animals has raised hopes among scientists that it is possible to achieve a similar feat in humans, or at least slow down the aging process. Anti-aging therapy could have a dramatic impact on public health by reducing the burden of age-related health problems , such as dementia, strokes and heart disease, and prolonging the quality of life of an increasingly aging population .
“What we saw in these animals was not a slowdown or stabilization of the aging process. We saw a dramatic change, and that was unexpected, ” said Ronald DePinho, who led the study, which was published in the journal Nature.
One of the most interesting things about this work is that the hypothetical clinical promise of this discovery is striking because it would not require brain surgery or any type of high-risk intervention. You could manipulate the cells systemically and achieve these results.
Focused on telomere shortening
In the study, blocking the interaction of a particular hormone and a receptor that is abundant in myeloid cells was sufficient to restore juvenile metabolism and behavior of human and mouse myeloid cells both in vitro and in live mice. This block also reversed age-related mental decline in older mice, restoring their memory and navigation abilities to those exhibited by young mice.
At Harvard, they bred genetically engineered mice that lacked an enzyme called telomerase that prevents telomeres from shortening. Without the enzyme, the mice aged prematurely and suffered from ailments, including a poor sense of smell, smaller brain size, infertility, and damaged intestines and spleens. But when the mice were given injections to reactivate the enzyme, the damaged tissues were repaired and the signs of aging were reversed.
The researchers found that myeloid cells experience an increasing propensity to accumulate glucose by converting this energy source into long chains of glucose called glycogen rather than “wasting” it for energy production. That hoarding, and the subsequent chronic state of energy depletion of cells, leads to great inflammation, wreaking havoc on aging tissues. “This powerful pathway drives aging,” comment the authors. “And it can be reversed.”
In humans?
Mice produce telomerase throughout their lives, but the enzyme is inactivated in adult humans . Increased levels of telomerase in humans may slow down the aging process, but increase the risk of cancer. The treatment appears to be safe in humans if given periodically and only to younger people who no longer have small clumps of cancer cells in their bodies.
Referencia: Paras S. Minhas, Amira Latif-Hernandez, Melanie R. McReynolds, Aarooran S. Durairaj, Qian Wang, Amanda Rubin, Amit U. Joshi, Joy Q. He, Esha Gauba, Ling Liu, Congcong Wang, Miles Linde, Yuki Sugiura, Peter K. Moon, Ravi Majeti, Makoto Suematsu, Daria Mochly-Rosen, Irving L. Weissman, Frank M. Longo, Joshua D. Rabinowitz, Katrin I. Andreasson. Restoring metabolism of myeloid cells reverses cognitive decline in ageing. Nature, 2021; DOI: 10.1038/s41586-020-03160-0
