Antibody therapy makes the immune systems of old mice young again

An experimental treatment restores the immune systems of older mice, improving the animals’ ability to fight off infections. If the therapy works in humans, it could reverse the age-related decline in immunity that makes older adults susceptible to disease.

These declines may be due to changes in our blood stem cells, which can develop into any type of blood cell, including some key components of the immune system.As we age, a greater proportion of these stem cells become more likely to produce some immune cells and not others, says Jason Ross at Stanford University in California. This imbalance impairs the immune system’s ability to fight infection. It also exacerbates chronic inflammation, which accelerates aging and increases the risk of age-related diseases such as heart disease, cancer, and type 2 diabetes.

Ross and his colleagues developed a treatment that targets these biased stem cells using antibodies or proteins that recognize and attack certain cells. They then tested the treatment on six mice aged 18 to 24 months, which is roughly equivalent to 56 to 70 years in humans.

One week after receiving the antibody injections, the mice had about 38% fewer abnormal stem cells compared with six rodents of the same age who did not receive treatment. They also had significantly increased numbers of two types of white blood cells that are critical for identifying and fighting pathogens, and lower levels of inflammation.

“You can think of it like stepping back in time,” Ross said. “We are making the proportions of these (immune) cells more similar to those in young adult mice.”

To test whether these changes would strengthen the immune system, the researchers vaccinated 17 older mice with a mouse virus vaccine. Nine of the mice had been treated with the antibody eight weeks earlier. The researchers then infected rodents with the virus. Two weeks later, they measured the number of infected cells in the animals and found that nearly half of the treated mice (four out of nine) had completely cleared the infection, compared with just one of eight untreated mice. The infection cleared.

Taken together, these findings suggest that antibody treatment can restore immune system vitality in aged mice. Because humans, like rodents, are also found to have an increase in abnormal blood stem cells with age, similar antibody treatments may also revive our immune systems, Ross said.

There is still a long way to go to say that this possibility Robert Signer at UC San Diego. On the one hand, we need to better understand the potential side effects of treatments.In the accompanying article, Signer and colleagues Yasar Alfat KasuResearch, also from UC San Diego, suggests that depleting stem cells, even abnormal ones, may increase the risk of cancer. On the other hand, “a better immune system will be better at detecting cancer. So we don’t know exactly what’s going to happen yet,” Signer said.

Still, the findings are a promising breakthrough in our understanding of age-related immune decline and how to mitigate it, Ross said.

Aging is the number one risk factor for many diseases. “By restoring or improving immune function in older adults, this really helps fight infection,” Signer said. “You may also have an impact on different types of chronic inflammatory diseases. That’s what’s exciting here.”