Immune Aging As A Failure Of Programmed Cell Death Coordination
As we get older, our bodies undergo many changes, and our immune system is no exception. It becomes less effective at fighting off infections and can even contribute to chronic inflammation, a state known as “inflammaging.” For a long time, scientists thought this decline was mainly due to issues with how immune cells developed or signaled.
However, new insights suggest a different, central mechanism: a disruption in how our cells naturally die. Our bodies have sophisticated ways of getting rid of old, damaged, or unnecessary cells through a process called programmed cell death. Think of it as a controlled demolition, essential for keeping our tissues healthy. One key type, called apoptosis, is a “silent” form of cell death that tidily disposes of cells without causing a fuss.
But as we age, this delicate balance goes awry. The coordinated effort among different cell death pathways breaks down. Instead of the clean, non-inflammatory apoptosis, aged immune cells tend to favor other forms of programmed cell death, such as necroptosis, pyroptosis, and ferroptosis. These are more “noisy” types of cell death, releasing signals that trigger inflammation.
This shift from silent to inflammatory cell death creates a vicious cycle. It leads to the accumulation of dysfunctional cells and cellular debris, which further fuels chronic inflammation. This persistent inflammation, in turn, contributes to the weakened immune responses and increased susceptibility to age-related diseases that we often see in older individuals. Understanding this fundamental change in how our cells die could open new avenues for therapies aimed at promoting healthier aging.
Source: link to paper