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    <h1>A Novel Anti-Aging Treatment Revitalized Mice Immune Systems — Will It Work In Humans?</h1>
    <p class="article-subtitle">One group of researchers believes they've found a way to reset the immune system with a one-time antibody treatment.</p>
    <div class="article-meta">
      <span class="author">By Miriam Fauzia</span> | 
      <time datetime="2024-03-27">March 27, 2024</time> | 
      <span class="source">Inverse</span>
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    <p>You might know your immune system as the built-in, around-the-clock surveillance system primed to keep nasty germs out and swiftly kick to the curb any that do manage to sneak in. It's a system primed to protect us at any age, but the sad truth is that once we get older, our immunity slows down and wanes.</p>

    <p>But what if there was a way to get back that pep in our immune step? Amidst a rising wave of anti-aging research seeking the keys to rejuvenation, one group of scientists led by Stanford University and the National Institutes of Health believe they've found a way to reset the immune system with a one-time antibody treatment.</p>

    <p>These findings were published in the journal <em>Nature</em>.</p>

    <h2>Myeloid versus lymphoid</h2>
    <p>The treatment relies on rebalancing a group of cells called hematopoietic stem cells (HSCs) that live in our bone marrow. These HSCs are the progenitors of other blood and immune system cells, and as we age, they tend to give rise to more blood, or myeloid, cells rather than lymphoid or immune cells like B and T cells. The researchers found that when older mice were given an antibody treatment targeting myeloid-making HSCs, this resulted in a stronger immune system that responded faster to vaccination and was less prone to unnecessary inflammation.</p>

    <blockquote>
      <p>“Older people just don't make many new B and T cell lymphocytes,”</p>
      <footer>— Irving Weissman, lead researcher and professor of pathology and developmental biology at Stanford University</footer>
    </blockquote>

    <p>“During the start of the Covid-19 pandemic, it quickly became clear that older people were dying in larger numbers than younger people. This trend continued even after vaccinations became available. If we can revitalize the aging human immune system like we did in mice, it could be lifesaving when the next global pathogen arises.”</p>

    <p>Lymphoid cells like B and T cells (also known collectively as lymphocytes) make up the adaptive immune system, which is more specific and strategic, and keeps a record of past tussles. Some myeloid cells also have immune functions, but they're part of another division called innate immunity. This system is non-specific and triggers responses like inflammation to help with protection and recruit other immune cells to the fold. While inflammation in and of itself isn't bad, it tends to stir up more and without due cause as we age, coining a phenomenon scientists have dubbed <strong>“inflammaging.”</strong></p>

    <p>Why some HSCs tend to make more myeloid cells — skewing the balance between myeloid and lymphoid cells — isn't entirely understood. But there's evidence to suggest that extremely long-lived people don't experience this skew and, as a result, retain protective B and T cells that help them mount fast and effective immune responses and likely less inflammation.</p>

    <h2>Rebalancing the immune force</h2>
    <p>In the new study, Weissman and his colleagues explored whether it was possible to realign HSCs with an antibody therapy. Because antibodies are very specific in who or what they target, the researchers needed to make sure they went after HSCs bending towards myeloid and not lymphoid cells. They examined the surfaces of mouse HSCs and found three proteins that singled out potential pro-myeloid versus lymphoid cells.</p>

    <p>Antibodies designed to seek out and destroy these myeloid-biased HSCs were injected into older mice, about 18 to 24 months of age (roughly equivalent to 56 to 69 years old in human years). The numbers of myeloid and lymphoid cells were measured one week, eight weeks, and 16 weeks later, and compared against younger mice aged three to six months old (roughly 20 to 30 human years). A control group of older mice received no treatment.</p>

    <p>After one week, the antibody-treated older mice demonstrated a considerable decrease in the number of pro-myeloid HSCs, and this effect was durable, lasting up to 16 weeks compared to untreated counterparts. The treatment did not harm HSCs inclined toward lymphoid cells, allowing significantly more new B and T cells to circulate.</p>

    <blockquote>
      <p>“Not only did we see a shift toward cells involved in adaptive immunity, but we also observed a dampening in the levels of inflammatory proteins in the treated animals,”</p>
      <footer>— Jason Ross, first author and postdoctoral medical fellow at Stanford University</footer>
    </blockquote>

    <p>“We were surprised that a single course of treatment had such a long-lasting effect. The difference between the treated and untreated animals remained dramatic even two months later.”</p>

    <p>The researchers also observed that when the antibody-treated older mice were vaccinated eight weeks later against a novel virus, their immune systems responded swiftly, closely trailing the response of younger mice.</p>

    <h2>Concerns for future research</h2>
    <p>As with many animal studies, results establish a precedent for potential human translation, though caution remains key.</p>

    <p>Writing in a commentary accompanying the study, stem cell biologist Robert Signer and Yasar Arfat Kasu of the University of California, San Diego, noted that while the research offers a promising new direction, open questions remain. Specifically, researchers wonder if the treatment could impact clonal hematopoiesis—an age-related phenomenon where specific HSC clones acquire genetic mutations, multiply, and potentially outcompete other cells.</p>

    <p>“[The authors] contend that targeted depletion of myeloid-biased HSCs could preferentially eradicate these dominant or pre-cancerous HSC clones. However, antibody conditioning could, in fact, exacerbate the emergence of clonal hematopoiesis by narrowing the total repertoire of HSCs,” write Signer and Kasu, which might accelerate progression toward cancer.</p>

    <p>Despite these concerns, Weissman and Ross remain optimistic that the findings will translate to humans, given that gene activation patterns in aged mice with myeloid-biased HSCs closely mirror those found in humans.</p>

    <p>“This is a real paradigm shift — researchers and clinicians should think in a new way about the immune system and aging,” Ross concluded.</p>
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