Antibody therapy makes the immune systems of old mice young again
An experimental therapy has been found to rejuvenate the immune systems of older mice, enhancing their capacity to combat infections. Should this treatment prove effective in humans, it could potentially reverse the age-related deterioration in immunity that renders older individuals more vulnerable to diseases.
This decline in immunity might stem from alterations in our blood stem cells, which have the potential to evolve into any blood cell type, including vital elements of the immune system. With age, an increasing number of these stem cells are inclined to generate certain immune cells rather than others, according to Jason Ross from Stanford University in California. Such an imbalance compromises the immune system's infection-fighting abilities and contributes to chronic inflammation, which hastens aging and heightens the risk of age-associated diseases like heart disease, cancer, and type 2 diabetes.
Ross and his colleagues developed a treatment using antibodies, or proteins that recognise and attack certain cells, to target these biased stem cells. They then tested the treatment in six mice between 18 and 24 months old, which is roughly equal to an age of 56 to 70 years in humans.
A week after receiving an antibody injection, the mice had about 38 per cent fewer of these aberrant stem cells, compared with six rodents of the same age that didn’t receive the treatment. They also had significantly greater amounts of two types of white blood cells crucial for recognising and combatting pathogens, as well as lower levels of inflammation.
“You can think of it as kind of turning back the clock,” says Ross. “We’re making the proportion of these [immune] cells more similar to [those of] a younger adult mouse.”
To test if these changes resulted in a stronger immune system, the researchers vaccinated 17 older mice against a mouse virus. Nine of these mice had received the antibody treatment eight weeks earlier. The researchers then infected the 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 only one of the eight untreated mice.
Together, these findings indicate the antibody treatment rejuvenates the immune system of old mice. Since humans, like rodents, also see aberrant blood stem cells increase with age, a similar antibody treatment may reinvigorate our immune systems too, says Ross.
Such a possibility is still a long way off, says Robert Signer at the University of California, San Diego. For one, we need to better understand potential side effects of the treatment. In an accompanying article, Signer and his colleague Yasar Arfat Kasu, also at the University of California, San Diego, suggest that depleting stem cells, even aberrant ones, could heighten the risk of cancer. On the other hand, “a better immune system is going to be better at surveying for cancers. So we just don’t know exactly what will happen yet”, says Signer.
Still, these findings are a promising breakthrough in our understanding of age-related immune decline and how to mitigate it, says Ross.
Ageing is the number one risk factor for a broad range of diseases. “By rejuvenating or improving immune function in older people, that could really help with fighting off infections,” says Signer. “You might also have an impact on different types of chronic inflammatory diseases. That’s what’s so exciting here.”
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