Reversing Immune Aging is an Important Goal

The immune system declines with age, becoming both less effective (immunosenescence) and at the same time overly inflammatory and active (inflammaging). It isn't just less effective when it comes to defending against infectious pathogens, but also in the matter of destroying senescent and potentially cancerous cells. Meanwhile, constant unresolved inflammatory signaling is disruptive to tissue structure and function, altering cell behavior for the worse. There are many possible approaches to at least somewhat reverse the underlying causes of these age-related dysfunctions of the immune system: restoring active thymic tissue; improving hematopoietic function; clearing malfunctioning and senescent immune cells; and so forth. More effort should be devoted to bringing these potential therapies to the clinic.

A stem-cell researchers didn't trust what they were seeing. Their elderly laboratory mice were starting to look younger. They were more sprightly and their coats were sleeker. Yet all the researchers had done was to briefly treat them - many weeks earlier - with a drug that corrected the organization of proteins inside a type of stem cell. In two papers, in 2020 and 2022, the team described how the approach extends the lifespan of mice and keeps them fit into old age. The target of this elixir is the immune system. The stem cells she treated are called haematopoietic, or blood, stem cells (HS cells), which give rise to all immune cells. As blood circulates, the mix of cells pervades every organ, affecting all bodily functions.

But the molecular composition of the HS cells changes with age, and this distorts the balance of immune cells that they produce. Recently another team showed that restoring the balance between two key types of immune cell gives old mice more youthful immune systems, improving the animals' ability to respond to vaccines and to stave off viral infections. Other scientists have used different experimental approaches to draw the same conclusion: rejuvenating the immune system rejuvenates many organs in an animal's body, at least in mice. And, most intriguingly, evidence suggests that immune system ageing might actually drive the ageing of those organs.

The potential - helping people to remain healthy in their later years - is seductive. But translating this knowledge into the clinic will be challenging. Interfering with the highly complex immune system can be perilous, researchers warn. So, at first, pioneers are setting their sights on important yet low-risk goals such as improving older people's responses to vaccinations and improving the efficiency of cancer immunotherapies. "The prospect that reversing immune ageing may control age-related diseases is enticing. But we are moving forward cautiously."


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