Table 1.

Common, Age-related Diseases That Involve Mitochondrial Abnormalities

Age-related Diseases	Prevalence	Mitochondrial Abnormalities
Aging	Aging is critical in several diseases that involve mitochondrial dysfunction.	DNA defects in the mitochondrial genome are responsible for aging and senescence. Accumulation of DNA defects is responsible for increased ROS production and oxidative damage in aged tissues.
Cancer	Most common in the aged (over 60 years of age).	Tumor cells excessively accumulate mitochondrial DNA defects and decrease mitochondrial respiration and ATP synthesis. Cancer cells up-regulate enzymes of glycolysis and adapt to decreased oxygen tension, a characteristic of most solid tumors.
Diabetes	Worldwide, 8% of the population suffers from diabetes.	Hyperglycemia causes pathological features of type 1 and 2 diabetes. Increased free radical production is found in hyperglycemia and has been found to disrupt glucose-stimulated insulin secretion by pancreatic beta cells.
AD	Worldwide, 5% of persons 65 years of age, and 50% of persons 85 years of age and older suffer from AD. 2% of the total number of AD patients have genetic mutations in APP, PS1, and PS2 genes.	Amyloid precursor proteins and amyloid beta are found in mitochondrial membranes and in the matrix of neurons affected by AD. Mitochondria APP and amyloid beta induce free radicals, decrease cytochrome oxidase activity, and inhibit ATP production. N-terminal ApoE4 is associated with mitochondria and causes mitochondrial oxidative damage.
PD	Worldwide, 0.5 to 1% of persons 65 to 69 years of age suffer from AD.	Both wild-type and mutant α-synuclein are found in the mitochondrial membranes and are determined to cause mitochondrial dysfunction. DJ1 is a redox sensor protein, localized to mitochondrial inter-membrane space and matrix. PINK 1 is a nuclear-encoded, mitochondrial kinase protein. Overexpression of PINK1 causes reduced mitochondrial membrane potential. Parkin is a gene product of Ubiquitin E3 ligase and is associated with the outer mitochondrial membrane. Parkin induces free radical production. LRRK2 is associated with the outer mitochondrial membrane and may induce free radicals. OMI/HTRA2 are pro-apoptotic serine proteases is a pro-apoptotic serine proteases found in the mitochondrial inter-membrane space.
HD	4–10 persons per 100,000 (mainly Caucasians) suffer from HD.	Mutant huntingtin binds to the outer mitochondrial membrane and induces free radical production. This induction is interrupted with calcium uptake. Mitochondrial movement is interrupted in mitochondria from HD neurons.
ALS	1–2 persons per 100,000 (variety of ethnic groups) suffer from ALS. 10% of the total number of ALS patients have genetic defects.	SOD1 is a cytosolic ROS scavenging enzyme. Mutant SOD1 aggregates have been found in the outer mitochondrial membrane, the inner mitochondrial membrane space, and the matrix. Mutant SOD1 induces free radicals and mitochondrial dysfunction in ALS patients.
Friedreich Ataxia	Worldwide, 1–2 persons per 100,000 (variety of ethnic groups).	Frataxin, the gene product of Friedreich ataxia, is a mitochondrial protein that is responsible for heme biosynthesis and the formation of iron-sulfur clusters. Mutations in frataxin facilitate the accumulation of iron in mitochondria, induce free radicals, and cause mitochondrial dysfunction.