A Pomegranate A Day Keeps The Doctor Away? Researchers Rejuvenate Aging Immune Systems

Our immune system weakens as we age, leaving us more vulnerable to infections, diseases, and tumors. New research has uncovered a key molecule that seems capable of curbing, and even reversing, this age-related decline in immune function. Published in Nature Aging, the findings provide yet another piece of the longevity puzzle, bringing us one step closer to meaningfully extending lifespan and health.

The “hematopoietic system” is the system in charge of producing our body’s blood cells. It is made up of various organs and tissues, including the bone marrow, the spleen, and lymph nodes. Think of blood as having two major functions: oxygenation and protection. Red blood cells take care of the first part of the equation by carrying oxygen around our body. White blood cells take care of the other part of the equation — they are our immune cells. These include all the usual suspects: B cells, T cells, macrophages, and so on.

White blood cells are made in the bone marrow. From there, they migrate into the blood and lymph nodes, where they are stored, ready to jump into action at the slightest hint of any microbial threat. Although our immune cells are highly complex, each with their own particular functions or specialties, they all spring from the same source: hematopoietic stem cells (HSCs). Stem cells are a unique class of cells that have the potential to “differentiate”, or develop, into any number of other cells. They’re a little like a fresh block of clay that has yet to be molded into a final work. Given their role as progenitor cells, hematopoietic stem cells are absolutely essential to a well-functioning immune system. If they are compromised, so, too, is our ability to manufacture the immune cells that protect us on a daily basis.

As incredible as stem cells are, they are not infallible; they also grow tired over time. We age and our stem cells age with us, slowly losing their ability to reconstitute the blood with all of the immune cells it needs. They also begin to develop a bias, preferentially producing one line of blood cells —the myeloid lineage— over the other. And crucially, hematopoietic stem cells accumulate an abnormal amount of mitochondria, the energy powerhouses of the cell, as we age. This interferes with the mitochondrias’ ability to perform their usual metabolic functions. Combined, these factors limit the production of immune cells and, by extension, our body’s ability to defend itself against toxins and pathogens.

Restoring Mitochondrial Health 

Nicola Vannini and the rest of his team at the University of Lausanne, Switzerland honed in on mitochondrial accumulation; since this was a key factor of age-related immune dysfunction, maybe there was some way of staving it off? Indeed, mitochondrial accumulation is just one aspect of a broader decline in metabolic efficiency seen in aging cells. Restoring metabolic function should have the knock-on effect of restoring blood-cell production.

A natural compound called urolithin A is known to improve metabolic fitness in both humans and rodents. It helps recycle mitochondria —replacing old with new— and prevents the cell from getting clogged up. This much had already been shown. But whether restoring mitochondrial recycling actually improved blood-cell production remained to be discovered.

Turning Old Mice Young Again

The group of researchers extracted hematopoietic stem cells from old mice and put them in a petri dish alongside urolithin A for three days. Afterwards, the hematopoietic stem cells were inserted into mice that had been exposed to lethal levels of irradiation. These mice, if left untreated, would succumb to complete hematopoietic failure: the radiation damages the hematopoietic stem cells, preventing them from being able to differentiate into blood cells. The mice were monitored and studied for a period of 24 weeks.

Lethally irradiated mice treated with the old stem cells exposed to urolithin A recovered just as quickly as those treated with stem cells from young mice — urolithin A had restored the old stem cells’ ability to reconstitute blood. And this effect was long-lived, lasting for the duration of the study.

To confirm their findings, the scientists performed a second experiment. This time, rather than directly exposing stem cells to urolithin A, they fed old mice a diet enriched with the immune-enhancing compound. The special diet boosted overall hematopoietic stem-cell performance and revitalized production of the lymphoid lineage, both of which are usually compromised with age.

Excitingly, rejuvenation of hematopoietic stem cells was reflected by improved immune response; old mice treated with urolithin A fared noticeably better than their non-treated counterparts at fighting viral infections.

Takeaways

This new work by the Vannini lab confirms that urolithin A rejuvenates hematopoietic stem cells and preserves their ability to produce blood cells of all types. Downstream, this leads to improved immune function and enhanced resilience in the face of infection. Urolithin A joins the ranks of klotho and platelet factor 4 (PF4) as a key player in aging and longevity.

Although it may be a while before these early successes are converted into consumer-ready therapies, the findings suggest that diet is an effective way of harnessing the health benefits of urolithin A; raspberries, walnuts, almonds, strawberries, and especially pomegranates are rich sources of the rejuvenating compound.