You may know that your immune system is a built-in, 24-hour surveillance system designed to ward off nasty germs and eliminate them instantly. It’s a system designed to protect us no matter our age. But sadly, as we age, our immune system weakens and weakens.
But what if there was a way to restore that vigor during the immune stage? Amid a growing wave of anti-aging research in search of the key to rejuvenation, a group of scientists led by Stanford University and the National Institutes of Health have found that one He believes he has discovered a way to reset the immune system with antibody treatments.
These findings were published Wednesday in the journal Nature.
myeloid and lymphatic system
This treatment relies on rebalancing a group of cells called hematopoietic stem cells (HSCs) that reside in the bone marrow. These HSCs are precursors to other blood cells and immune system cells, and as we age, they produce more blood cells and myeloid cells, rather than lymphoid and immune cells such as B cells and T cells. There is a tendency to Researchers found that treating older mice with an antibody treatment that targets myeloid HSCs made their immune systems stronger, more responsive to vaccinations, and less prone to unnecessary inflammation.
“Older people make fewer new B and T cell lymphocytes,” Irving Weissman, the study’s principal investigator and professor of pathology and developmental biology at Stanford University, said in a press release. . “When the COVID-19 pandemic began, it quickly became clear that older people were dying more than young people. This trend continued as vaccination became available. “If we can activate the immune system in aging humans, as we did in mice, it could be a lifesaver during the next global pathogen outbreak.”
Lymphoid cells such as B cells and T cells (also collectively called lymphocytes) constitute a more specific and strategic adaptive immune system and keep records of past conflicts. Some bone marrow cells also have immune functions, but they are part of a separate branch called innate immunity. This system is non-specific and triggers responses such as inflammation to aid in defense and recruit other immune cells into the fold. Inflammation itself isn’t a bad thing, but as we age, it tends to become more intense for no good reason, a phenomenon scientists call “inflammation.”
It is not fully understood why some HSCs tend to generate more myeloid cells, thus skewing the balance between myeloid and lymphoid cells. However, very long-lived people do not experience this bias and, as a result, retain protective B and T cells that mount a rapid and effective immune response and perhaps help reduce inflammation. There is evidence to suggest that.
restore balance to immunity
In the new study, Weissman and his colleagues investigated whether it is possible to rebalance HSCs with antibody therapy. Antibodies are very specific in who or what they target, so researchers need to ensure that they track HSCs toward myeloid cells rather than lymphoid cells. They examined the surface of mouse HSCs and found three proteins that identified them as potentially promyeloid cells compared to lymphoid cells.
Antibodies designed to seek out and destroy these myeloid-biased HSCs were injected into older mice, about 18 to 24 months old (equivalent to about 56 to 69 years of age in humans). He measured the numbers of myeloid and lymphoid cells after 1, 8, and 16 weeks. They compared that number with young mice, who are 3 to 6 months old, or about 20 to 30 years old in human years. One group of older mice received no treatment.
After one week, older mice treated with the antibody showed a significant reduction in the number of promyeloid HSCs, and this effect appeared to be quite durable, lasting up to 16 weeks compared to untreated mice. The treatment did not harm HSCs, which tend toward lymphoid cells. Many more new B and T cells were circulating in the animals.
“Not only did we see changes to cells involved in adaptive immunity, but we also observed reduced levels of inflammatory proteins in treated animals,” said Jason, lead author of the paper and a postdoctoral fellow at Stanford University. Ross said. In a press release. “We were surprised that a single treatment had such a long-lasting effect. The differences between treated and untreated animals remained dramatic even after two months. did.”
The researchers also vaccinated older mice treated with antibodies against a virus to which they had never been exposed eight weeks later, and found that their immune systems responded quickly and in a way that was not quite the same as in younger mice. However, it was also confirmed that the reaction was almost the same.
Concerns about future research
Like many studies in animals, these studies have set a precedent that humans may reap similar benefits, but their parallel progress means that our mileage may be limited. Be warned that it can be long. Wide Change.
In a commentary accompanying the study, stem cell biologists Robert Signer and Yasar Alfat Kass of the University of California, San Diego, say the study presents an interesting new direction for rejuvenating the aging immune system. He said there was. But in particular, this new antibody treatment may impact clonal hematopoiesis, an age-related phenomenon in which groups of HSCs carry the same genetic mutations and begin to proliferate, potentially outweighing and overwhelming all other HSCs. There are still unknowns and concerns about whether or not it may be possible to give. .
“[The authors of the new paper] We argue that targeted depletion of myeloid-biased HSCs may enable preferential eradication of these dominant or precancerous HSC clones. However, in reality, antibody conditioning may exacerbate the emergence of clonal hematopoiesis by narrowing the total repertoire of his HSCs,” Signer and Arfat Kass wrote. The researchers added that this could actually accelerate “progression to cancer.”
But Wiseman and Ross found that the pattern of genes that are turned on in older mice with myeloid-biased HSCs is similar to that seen in humans, so what they demonstrated in mice works well in humans. I hope that it will be useful for the
“This is a real paradigm shift. Researchers and clinicians need to think about the immune system and aging in new ways,” Professor Ross said. “The idea that we can modulate the entire immune system of millions of cells simply by influencing the function of such a rare population is surprising and exciting.”
