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Advancing age is a major risk factor for malignant transformation and the development of cancer. As such, over 50% of neoplasms occur in individuals over the age of 70. The pathologies of both ageing and cancer have been characterized by respective groups of molecular hallmarks, and while some features are divergent between the two pathologies, several are shared. Perturbed mitochondrial function is one such common hallmark, and this observation therefore suggests that mitochondrial alterations may be of significance in age‐related cancer development. There is now considerable evidence documenting the accumulation of somatic mitochondrial DNA (mtDNA) mutations in ageing human postmitotic and replicative tissues. Similarly, mutations of the mitochondrial genome have been reported in human cancers for decades. The plethora of functions in which mitochondria partake, such as oxidative phosphorylation, redox balance, apoptosis and numerous biosynthetic pathways, manifests a variety of ways in which alterations in mtDNA may contribute to tumour growth. However, the specific mechanisms by which mtDNA mutations contribute to tumour progression remain elusive and often contradictory. This review aims to consolidate current knowledge and describe future direction within the field. [ABSTRACT FROM AUTHOR]

There is strong evidence that mitochondrial DNA mutations and mitochondrial dysfunction play a role in diabetes pathogenesis. The homozygous knock-in mtDNA mutator mouse is a model of premature aging due to the accumulation of mitochondrial DNA mutations. We used this mouse model to investigate the relationship between mitochondrial subunit expression and pancreatic islet cell composition. Quadruple immunofluorescence was used to quantify mitochondrial subunit expression (complex I and IV) and cell composition in pancreatic islets from mitochondrial DNA mutator mice (PolgA mut/mut ) and control C57BL/6 mice at 12 and 44 weeks of age. Mitochondrial complex I subunit expression was decreased in islets from 12 week PolgA mut/mut mice. This complex I deficiency persisted with age and was associated with decreased insulin staining intensity at 44 weeks. Complex I deficiency was greater in α-cells compared with β-cells in islets from 44 week PolgA mut/mut mice. Islet cell composition was normal in 12 week PolgA mut/mut mice, but the β: α cell ratio was decreased in islets from 44 week PolgA mut/mut mice. This was due to an increase in α-cell number linked to an increase in α-cell proliferation. Complex I deficiency promotes α-cell proliferation and alters islet cell composition. • Decreased islet complex I expression was established in PolgA mut/mut mice at 12 weeks. • Decreased islet complex I expression was associated with increased pancreatic α-cell number in PolgA mut/mut mice at 44 weeks. • Increased α-cell proliferation contributes to the increased α-cell number. [ABSTRACT FROM AUTHOR]