Mutations in mitochondrial DNA may play a role in the progressive symptoms of late-onset diseases, such as Parkinson's and Alzheimer's diseases. In Parkinson's disease, brain cells that use dopamine as a neurotransmitter are selectively killed. Defects in the mitochondria of those neurons have been observed in patients with the disease. And some have proposed that the presence of increased oxygen free radicals and their accumulated effects during aging may contribute to the disease. Oxidative damage to mitochondrial function might explain why the risk of Parkinson's increases with age and why there has rarely been evidence that the disease has a familial pattern of inheritance.

As in Parkinson's disease, Alzheimer's patients suffer the loss of neurons, but the losses are more diffuse, taking place in large areas of the brain, and are concentrated in the lobes of the brain that control some of the higher intellectual functions. One characteristic of Alzheimer's disease is the accumulation of beta amyloid aggregates, or plaques. Beta amyloid is produced from a larger protein involved in cell membrane function. The pathology seen in Alzheimer patients may involve oxidative stress, leading to neuronal degeneration in the brain.

Dilated cardiomyopathy is a serious heart condition that is age-related. Often referred to as "enlarged heart," its telltale sign is a thickening of the muscular walls of the heart, particularly the walls of the left ventricle, the chamber that carries the burden of pumping blood into the general circulation. In cardiomyopathy, the ventricle becomes stiff and loses its ability to pump blood effectively, a serious condition known as heart failure. Heart muscle is metabolically very active, making it especially sensitive to mitochondrial abnormalities. A study of patients with cardiomyopathy found that older patients were more likely to have multiple defects in mitochondrial enzymes, and they were also more likely to have defects in their mitochondrial DNA.

The risk of type 2 (late-onset) diabetes increases with age and with obesity. One feature of type 2 diabetes is insulin-resistance - the inability of tissues to respond to normal levels of insulin. In some individuals, insulin secretion can be affected as well. Certain mutations in mitochondrial DNA are associated with decreased production of insulin by the pancreas. Further, skeletal muscle uses a great deal of oxygen, and insulin keeps its metabolism under tight control. Abnormalities resulting from mutations in mitochondrial DNA associated with aging are thought to contribute to some instances of insulin resistance in muscle. In fact, it has been proposed that the progressive increase in the incidence of type 2 diabetes with age parallels the "normal" aging pattern, which is associated with increased injury to mitochondrial DNA and decreased energy production.