Ageing cells fuel inflammation through their mitochondria
Senescent cells stop dividing but do not go quiet. They continuously send inflammatory signals to surrounding tissue. New research reveals a second way the cell’s energy factories power that process.
Senescent cells, which have permanently halted division due to damage or replication limits, produce a broad cocktail of inflammatory molecules known as the SASP (the senescence-associated secretory phenotype). It was already known that mitochondria contribute by releasing DNA fragments that trigger an internal alarm signal. The study now describes a second layer: mitochondrial metabolism also directly supplies the raw material for inflammation.
The pyruvate-citrate axis as an inflammatory engine
In senescent cells, the pyruvate-citrate-acetyl-CoA axis within mitochondria is upregulated. This metabolic pathway normally generates energy. In senescent cells it also produces elevated levels of acetyl-CoA, a molecule used to chemically modify histones, the proteins around which DNA is coiled. These histone modifications determine which genes are switched on. Here, the extra acetyl-CoA activates inflammatory gene programmes.
The protein SLC25A1 is a transport molecule in the mitochondrial membrane that exports citrate, a necessary step in the chain. When the researchers inhibited SLC25A1, inflammatory signalling from senescent cells was reduced, identifying it as a potential therapeutic target.
Dampening rather than destroying
Two strategies exist for dealing with senescent cells: destroy them selectively or suppress their harmful behaviour. This research falls in the second camp. The findings are currently cell-biology work; whether SLC25A1 inhibition is safe and effective in humans remains to be tested. Nevertheless, identifying this metabolic node offers a new angle for addressing the chronic low-grade inflammation that characterises aging tissue, without eliminating the cells themselves.
Search terms to explore further: SASP mitochondrial metabolism, histone acetylation inflammation aging, cellular senescence inhibition