RNA-DNA structures in aging cells drive body-wide inflammation
Aged cells cause inflammation throughout the body. Now researchers have identified a specific mechanism that drives this process. It involves structures found in the cell’s interior that are not normally supposed to be there.
When a cell ages and stops dividing, it enters a state called senescence. The cell does not die, but it also stops doing its normal work. What it does do is actively secrete inflammation-promoting substances. This collection of secreted factors is called the SASP (senescence-associated secretory phenotype). The SASP is one of the main reasons senescent cells are harmful to surrounding tissues.
Exactly how the SASP is regulated was not fully understood. The researchers have now found that so-called R-loops (three-stranded structures where RNA binds to DNA inside the cell nucleus) play a role. Normally, R-loops help repair DNA damage. But in senescent cells, they accumulate, escape into the cytoplasm outside the nucleus, and trigger an alarm response there that produces inflammatory signals.
RNA in the wrong place
The problem is not that R-loops exist, but that in senescent cells they are not properly resolved and leak out of the nucleus. Once in the cytoplasm, they are recognised as foreign signals, similar to how the immune system responds to invading viruses. This activates an inflammatory response. In senescent cells, this leads to secretion of inflammation-promoting substances that damage surrounding tissue.
This finding is relevant to longevity research because it offers a new target. If it becomes possible to reduce the accumulation or leakage of R-loops, the SASP might be partly suppressed. Whether that is technically and safely feasible is another question, the study provides mechanistic insight, not a therapy.
Systemic inflammation as a driver of aging
Aging is accompanied by a gradually rising level of chronic inflammation throughout the body. Senescent cells contribute to this via their SASP. This research provides a more concrete explanation for how that contribution arises, namely through RNA-DNA structures accumulating in the cytoplasm, keeping the immune system in a state of low-grade activation.