Age-Related Deterioration of Mitochondrial Function in the Intestine

Table 1

Most relevant studies regarding the role of mitochondria and their alterations in the aging intestine.

Reviewed study	Model	Organ	Cell	Observed findings/alterations
Anton-Erxleben et al. 1983	Drosophila melanogaster	Midgut	Epithelial cells	The midgut epithelium of aged Drosophila melanogaster was found to exhibit mitochondria with disarranged cristae and also crista-free areas. Additionally, mitochondria showed accumulation of dense bodies, virus-like particles, and fiber-shaped and reticular structures.
Taylor et al. 2003	Human	Colon	Crypt stem cells	COX deficiency or complete crypt loss throughout the colon specimens. Mitochondrial-encoded subunits I and II of complex IV showed absence of immunoreactivity in COX-deficient crypts in all patient samples. The nuclear-encoded subunit IV showed a similar pattern, but to a lesser extent.
Greaves et al. 2010	Human	Colon	Mucosal cells	11.2% of the crypts showed no or reduced expression of one or more complexes, and the frequency increased exponentially with age. A number of point mutations affecting mitochondrial-encoded RC subunits were observed.
Zhang 2010	Mice	na	na	In chronic alcohol consumption in mice, mtDNA damage was seen and IL-6 was shown to be important for the recovery of the liver from mtDNA oxidation. IL-6 knockout and wild-type mice were fed with ethanol for 4 weeks, which led to mtDNA injury in both groups. In contrast to IL-6 knockout mice, wild-type mice were able to activate repair mechanisms and avoid mtDNA mutations.
Fox et al. 2012	Mice	Small intestine	Intestinal stem cells, progenitor cells	mtDNA-polymerase γ (PolgD257A) mutated mice were examined for structural changes in the crypts of Lieberkühn.; Significant enlargement and 10-fold increase in apoptosis in the small intestine.; Significantly decreased migration along the crypt-villus axis and significant decline in lipid absorption, leading to increased fecal excretion of lipids, compared to wild-type mice.
Tuo et al. 2012	Mice	Duodenum	Mucosal cells	Reduced basal and stimulated duodenal bicarbonate secretory rates in late-generation (G3) telomerase-deficient (mTERC^-/-) mice in comparison to those of age-matched wild-type mice. Slimming and shortening of villi of the duodenal mucosa. Telomere shortening induces an imbalance between harmful and protective secretory products in the duodenum, leading to an increased risk of ulcer formation.
Lowes et al. 2013	Rats	na	na	Antioxidants which protect mitochondria (MitoQ, MitoE, or melatonin) also lower IL-6 levels and oxidative stress and thereby improving mitochondrial activity and reducing organ dysfunction in the case of acute sepsis.
Tran and Greenwood-Van Merced 2013	Baboons	Colon	Epithelial cells	Old baboons had greater expression of interferon gamma (IFN-γ), IL-6, and IL-1β, linked to a disruption of intestinal permeability.
Man et al. 2015	Human	Terminal ileum	Epithelial cells	Upregulation of IL-6 in terminal ileum biopsies, but no effects on IFN-γ, TNF-α, and IL-1β expression were noted in the elderly compared to young people, and ileal permeability to macromolecules was unchanged.
Özsoy et al. 2020	Human	Colon	Mucosal cells	The protein expression levels of OXPHOS complexes increased from childhood into adulthood and then decreased in elderly individuals, while the numbers of crypts with partial or complete loss of expression of complexes I and IV increased continuously with age.