How mitochondrial failure triggers cellular senescence and chronic inflammation

This review synthesizes current understanding of how failing mitochondria—the cell's power plants—create a vicious cycle leading to cellular senescence and chronic inflammation ("inflammaging"). When mitochondria lose efficiency, they produce less energy and more reactive oxygen species, triggering stress responses. Critically, dysfunctional mitochondria release their DNA and other damage signals into the cell's interior, activating inflammatory pathways. This creates senescent cells that secrete pro-inflammatory factors, further damaging neighboring cells' mitochondria. The paper maps these mechanistic bridges in detail, showing how bioenergetic failure isn't just a consequence of aging but an active driver. For longevity science, this matters enormously: if mitochondrial dysfunction is upstream of senescence and inflammaging—two central aging mechanisms—then interventions targeting mitochondrial health (NAD+ precursors, mitophagy enhancers, mitochondrial-targeted antioxidants) might address multiple aging pathways simultaneously. The review provides a framework for understanding why diverse longevity interventions often improve mitochondrial function, and why mitochondrial quality control remains a prime therapeutic target.