Mitochondria are indispensable for cellular energy, and their decline is associated with ageing and disease, which is firmly supported. The most concrete and well-supported handle for influencing that decline is endurance exercise, through activation of PGC-1alpha and AMPK. Other routes, such as RNA structures or cellular mitochondrial transport, are still at an early stage of research and have not been translated into practical advice for healthy people.
Mitochondria are tiny structures found in virtually every cell of your body that act as power plants. They convert nutrients into ATP, the energy currency cells use for almost everything: muscle contraction, brain activity, cell repair. But they do more than produce energy: they are also involved in making molecular building blocks, removing waste products, and maintaining the balance between harmful and harmless molecules inside the cell. When mitochondria do not function properly, this can contribute to a wide range of conditions, from diabetes and heart failure to neurodegenerative diseases and cancer. Mitochondrial function also gradually declines with normal ageing.
Cells maintain their mitochondria through their own quality-control system. Damaged or worn-out ones are cleared away through a process called mitophagy, while mitochondria can also be split or merged (fission and fusion) to keep the population in optimal shape. Disruptions in this system are associated with ageing and disease. This is not the finding of a single study but a mechanism described across multiple lines of research and considered likely to be causal.
The question of whether you can make mitochondria 'younger or more energetic' has the most concrete support for physical exercise, particularly endurance exercise. Endurance exercise activates a protein called PGC-1alpha, which acts as a master switch for the production of new mitochondria in muscle cells. The same protein also directs quality control, including mitophagy and fusion/fission. In addition, PGC-1alpha activation improves insulin sensitivity in muscles. This is the best-studied and biologically best-understood mechanism for influencing mitochondrial decline, though the bulk of the evidence comes from animal and laboratory studies plus mechanistic human research, not from large randomised trials.
A second route runs through the protein AMPK, an energy sensor that springs into action when the cell has little ATP, such as during exercise, caloric restriction, or the use of the diabetes drug metformin. AMPK promotes mitophagy, among other things, and helps clear out damaged mitochondria. This is an evolutionarily ancient mechanism that is well documented, but the translation into concrete lifestyle advice beyond exercise is still largely based on animal and mechanistic research.
There are also more experimental directions. Laboratory studies, mainly in cancer cells, show that certain RNA structures called G-quadruplexes can influence the production of mitochondrial proteins. And cells appear to be able to physically exchange mitochondria through thin connecting tubes. These are interesting discoveries, but they are still at an early stage of research and have been studied primarily in cancer cells. Whether they are relevant for healthy people or for ageing cannot be determined on the basis of the available evidence.
Finally, a practical note on measurement. Many products or treatments claim to bring about mitochondrial improvement, but the gold standard for measuring mitochondrial function, the so-called respiratory control ratio plus membrane potential, is rarely used in such claims. Many popular measurement methods are less reliable. This makes it difficult to assess the value of commercial claims about 'mitochondrial supplements'.
Claims are based on mechanistic reviews, animal studies, and laboratory research, supplemented by observational and mechanistic human research. No large randomised trials are available that specifically measure mitochondrial rejuvenation as an endpoint. The causal link between mitochondrial dysfunction and disease/ageing is strongly supported; the interventional side (what concretely helps) is less mature.