Page 29 - ITPS-7-2

INNOSC Theranostics and
Pharmacological Sciences Mitochondria and aging

tocopherols and tocotrienols, was previously demonstrated by reducing oxidative stress damage (Figure 1[i–ii]).
to extend the life span and decelerate aging in different Paradoxically, some animal models, such as C.elegans, with
species. 169,170 Vitamin E compounds seem to extend life CoQ biosynthetic deficiencies have shown an increase in
span in various ways, including ameliorating age-related life span. 188,189 This observed effect might be attributed to
decline in NO synthase and SOD2, suppressing ROS the maintenance of the efficiency of respiration together
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production, reducing ROS damage (Figure 1[i–ii]), with an observed reduction in the production of superoxide
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mitigating ethanol-induced accumulation of intracellular anion in the mitochondrial electron change, which would
oxidants and counteracting the suppression of glutathione cause lower damage to macromolecules in response to
peroxidase/glutathione reductase, providing protection CoQ silencing. However, these data cannot be extrapolated
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against age-related hepatocytes polyploidization, and to other biological systems, such as mammals.
neuroprotection by reducing the quantity of p53-positive
cells throughout the brain. Furthermore, antioxidant- 6. Mitochondrial dysfunction leads to stem
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based therapy involving the use of natural sources of cell exhaustion
antioxidants such as Vitamin E and Coenzyme Q (CoQ, One of the hallmarks of aging is the reduction in stem
ubiquinone) appears to be effective in animal models cell numbers due to their impaired self-renewal capacity
of neurodegenerative disease, including mouse models and function. Studies show that as hematopoietic stem
of both PD and AD. CoQ10 is naturally generated cells (HSC) age, they exhibit increased mitochondrial
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in the body and serves as an antioxidant agent, and its OXPHOS and enhanced ROS production, indicating a
level declines in the body during aging. CoQ10 is direct role for mitochondria in the degenerative process.
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mostly found in the inner mitochondrial membrane of Studies show that ROS at low levels plays a positive role in
eukaryotic cells. Furthermore, it acts as an electron stem cell biology, mainly by maintaining their stemness,
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shuttle between complexes I and II of the respiratory quiescence, and self-renewal. 190-192 However, elevated ROS
chain, as well as complex III in mitochondria. As a can activate stem cell differentiation, senescence, and
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result, it can exist in both oxidized (CoQ or ubiquinone) apoptosis, resulting in their exhaustion, which is linked
and reduced (CoQH2 or ubiquinol) forms. Furthermore, with the aging process and degenerative diseases. 190,193
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CoQ10 protects against oxidative stress-induced cell In addition, low amounts of ROS can act as a signaling
death. Studies show that CoQ10 protects the skin by molecule to promote cardiovascular differentiation
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combating free radicals, which were shown to damage in mouse embryonic stem cells (mESCs). Meanwhile,
collagen fibers through the activating MAPK pathway high amounts of ROS can lead to the inhibition of
that produces matrix metalloproteinases (MMPs) such cardiomyogenesis and vasculogenesis. Similarly, ROS at
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as collagenase. 181,182 Aberrations in CoQ10 biosynthesis low levels allows HSCs to keep up their normal functions,
genes cause primary CoQ10 deficiency, a mitochondrial including proliferation, differentiation, and mobilization.
syndrome associated with impaired OXPHOS and Interestingly, several studies on POLG mtDNA mutator
clinically heterogeneous diseases, including cerebellar mice showed impairment of stem cell functions and found
ataxia, encephalomyopathy, infantile multisystemic form, a wide range of defects, including impairment of neural
isolated myopathy, and nephropathy. 177,178 Reportedly, stem cell (NSC) populations, megaloblastic anemia,
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some patients also developed retinopathy or optic atrophy, B-cell abnormalities, and impaired reprogramming
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hypertrophic cardiomyopathy, and sensorineural hearing capacity into pluripotent stem cells due to increased ROS
loss as a result of CoQ10 deficiency. In addition, CoQ10 levels. In addition, transplantation of HSCs from POLG
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deficiency is connected with mtDNA point mutations, mtDNA mutator mice into a normal host led to the same
depletion, and deletions. Nonetheless, Coenzyme Q observed defect. Another study demonstrated that the
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supplementation was demonstrated to protect against age- ability of POLG knockin cells to be reprogrammed into
related DNA double-strand breaks and prolong longevity pluripotent stem cells is likewise significantly reduced;
in mice who consumed a polyunsaturated fatty acid this deficiency is once again linked to an increase in the
(PUFA)-rich diet by attenuating oxidative alterations. 197
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CoQ10 supplementation may improve human lymphocyte production of ROS by the mitochondria. Taken together,
recovery from oxidative DNA damage due to the ordering studies on the POLG mtDNA mutator mice clearly linked
and condensing impact of CoQ10 on cell membranes, mitochondria to stem cell functions, suggesting the POLG
resulting in a decrease in ROS formation and a protective mtDNA mutator mice influence a wide range of cell types,
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benefit to DNA integrity. Nonetheless, lifetime CoQ10 including stem cells, their offspring, and the niche.
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treatment had no effect on the lifespan of rats or mice, Mitochondria can also help to maintain stem cells by
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indicating that CoQ10 might aid in preventing life span regulating particular metabolites that act as secondary
shortening as a result of cumulative oxidative insults messengers for epigenetic regulation. Numerous crucial
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Volume 7 Issue 2 (2024) 7 doi: 10.36922/itps.1726