Should younger and older people receive different treatments for the same infection?

Dealing with an infection isn’t as straightforward as simply killing the pathogen. The body also needs to carefully steer and monitor its immune response to prevent collateral damage. This regulation, called disease tolerance, is crucial to protecting our tissues while the immune system tackles the infection head-on. To survive an infection, your body must activate a tolerance mechanism that is compatible with the specific progression of your disease. So, if your body is changing over the course of your lifetime, does that mean the specific mechanisms it uses to survive an immune onslaught change, too? Salk scientist Janelle Ayres , PhD, has spent the past two decades studying disease tolerance, and this question is the latest to cross her lab bench. The answer, published in Nature on January 14, 2026, is that younger and older mice with sepsis-a life-threatening exaggerated response to infection-have distinct disease courses and tolerance mechanisms. What’s more, the genes and proteins that protected young survivors from sepsis-induced multi-organ damage and death had the opposite effect in older survivors. The mechanisms young mice used to survive sepsis were the very same mechanisms that caused older mice to die, suggesting that future therapies may be more effective if tailored to the patient’s age. New sepsis treatments are especially needed as the antibiotic resistance crisis continues to threaten current care strategies. “There are many cases where a patient’s body successfully kills the infectious pathogen, but the patient still dies-I want to understand why, ” says Ayres, senior author of the study, Howard Hughes Medical Institute Investigator, and professor and holder of the Salk Institute Legacy Chair at Salk. “It’s not just the pathogen that can hurt us; it’s our own responses to those pathogens. The focus of my lab has been to elucidate the disease tolerance strategies our bodies use to manage that self-inflicted damage. Dissecting those strategies may lead us to more effective therapies and a way around the antimicrobial resistance crisis.” What is sepsis? The immune system is a powerful ally. Many organs, cells, and molecules combine to form a united front against invaders like the flu or dysfunctions like cancer. Sometimes, however, the immune system focuses too tightly on eliminating the threat and forgets that its attacks have repercussions on the rest of the body as well. Sepsis is an extreme example of the damage the immune system can do when it overreacts. In this condition, the immune system sets out to attack a bacterial, fungal, viral, or parasitic infection, but that protective response quickly spirals out of control. So out of control, in fact, that sepsis can cause multi-organ failure and death. The threat of sepsis is enormous-anyone can get it, and sepsis-related deaths make up 20 percent of all global deaths. So, how do we treat it? Antibiotics are the first medication deployed. However, the patient’s immune response is doing so much more damage than the pathogen those antibiotics are targeting, and the growing threat of antibiotic resistance also adds concern about the overuse...

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