Targeting cell metabolism to clear aging cells
Senescent cells accumulate in the body over time and fuel chronic inflammation. Researchers have now found a new way to destroy them by exploiting a quirk in their own energy metabolism.
Senescent cells are cells that have stopped dividing but refuse to die. They continuously secrete inflammatory proteins, a property known as the senescence-associated secretory phenotype, or SASP. These secretions damage surrounding tissue and are linked to age-related conditions. The researchers found that senescent cells burn more sugar than normal cells through a process called glycolysis, and that this elevated glycolysis supports their survival.
More specifically, they identified an interaction between two proteins, PGAM1 and CHK1, that boosts glycolytic activity and cell viability in senescent cells. Blocking this interaction disrupted the cells’ energy supply and caused them to die. At the same time, the output of inflammatory SASP factors was reduced.
Effects seen in animal models
In animal experiments, inhibiting the PGAM1-CHK1 interaction reduced organ damage and lessened pulmonary fibrosis, a condition in which scar tissue builds up in the lungs. These are encouraging results, but the gap between animal models and human application remains large. Whether a drug targeting this interaction would be safe and effective in people has yet to be established.
A new route to clearing aging cells
Several compounds already exist that can kill senescent cells, but the search for more precise approaches continues. This new target is of interest because it exploits a metabolic property that appears specific to senescent cells, which in principle offers selectivity. From a longevity perspective, this is a relevant addition to a growing research field, though it remains at an early stage.
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