In short
Mitochondrial dysfunction refers to the age-related decline in mitochondrial number, efficiency, and quality control that reduces a cell's capacity to produce ATP and manage oxidative stress.
Mitochondria generate most of a cell's ATP through oxidative phosphorylation, a process that also produces reactive oxygen species (ROS) as a byproduct. With age, several things tend to go wrong together: mitochondrial DNA (which lacks the same repair machinery as nuclear DNA) accumulates mutations, mitochondrial number and membrane potential decline, and mitophagy — the selective autophagic clearance of damaged mitochondria — becomes less efficient, allowing dysfunctional mitochondria to accumulate.
This decline is tissue-specific and shows up most visibly in high-energy-demand tissues: skeletal muscle (contributing to sarcopenia), the heart, and neurons. Studies measuring mitochondrial respiratory capacity in human muscle biopsies show a clear age-related decline, and this decline correlates with reduced VO2 max and physical function in older adults.
Exercise, particularly high-intensity and resistance training, is the most robustly evidenced intervention for improving mitochondrial function in humans — it stimulates mitochondrial biogenesis via pathways including AMPK and PGC-1α. Compounds like NAD+ precursors, PQQ, and urolithin A are marketed on the premise of supporting mitochondrial function or mitophagy, and some have early human biomarker data (urolithin A, for instance, has published human trials showing improved muscle mitochondrial biomarkers), but none has been shown to reverse age-related mitochondrial decline at the level exercise does.