Role of Reactive Oxygen Species in Aging and Age-Related Diseases: A Review

Anik, Muzahidul I.; Mahmud, Niaz; Masud, Abdullah Al; Khan, Ishak; Islam, Nurul; Uddin, Shihab; Hossain, M. Khalid

doi:10.1021/acsabm.2c00411

Cited by 61 publications

(41 citation statements)

References 350 publications

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“…Genes that compose Complex I and Complex III of the electron transport chain (ETC) were significantly enriched for positive selection. These complexes are hypothesized to be the primary source of reactive oxygen species production in the ETC, where a severe abundance of reactive oxygen species has been linked to several age-related diseases 51,52 . In contrast to the germline, the mt-genome is predominantly shaped by positive selection in somatic tissues; yet, the effects that these mutations have at the mitochondrial and cellular level along with the advantages these mutations confer remains to be explored.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection throughout aging

Serrano

Hirose

Valentine³

et al. 2023

Preprint

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Mitochondrial genomes co-evolve with the nuclear genome over evolutionary timescales and are shaped by selection in the female germline. Here, we investigate how mismatching between nuclear and mitochondrial ancestry impacts the somatic evolution of the mt-genome in different tissues through aging. We used ultra-sensitive Duplex Sequencing to profile ~2.5 million mt-genomes across five mitochondrial haplotypes and three tissues in young and aged mice, cataloging ~1.2 million mitochondrial somatic mutations. We identify haplotype-specific mutational patterns and several mutational hotspots, including at the Light Strand Origin of Replication, which consistently exhibits the highest mutation frequency. We show that rodents exhibit a distinct mitochondrial somatic mutational spectrum compared to primates with a surfeit of reactive oxygen species-associated G>T/C>A mutations and that somatic mutations in protein coding genes exhibit strong signatures of positive selection. Lastly, we identify an extensive enrichment in somatic reversion mutations that "re-align" mito-nuclear ancestry within an organism's lifespan. Together, our findings demonstrate that mitochondrial genomes are a dynamically evolving subcellular population shaped by somatic mutation and selection throughout organismal lifetimes.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection throughout aging

Serrano

Hirose

Valentine³

et al. 2023

Preprint

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“…Hydrophilic OVA was disseminated and stabilized in a hydrophobic IPM solution in ILNDFs utilizing LBIL-([EDMPC][Lin]) and cationic/anionic/non-ionic conventional surfactants at a 1:1 w/w ratio ( Figure 1 A). DLS was used to measure the particle size (n/z) and PDI of the ILNDFs (summarized in Table 1 ), and the particle size was approximately or below 500 nm in all formulations ( Figure S2i ), which is suitable for TDDSs [ 4 , 29 , 30 ]. The CLSM observation confirmed that the FITC-OVA nanoparticles moved freely in the IPM, and the particle size agreed well with the DLS observation ( Figure S2i,ii ).…”

Section: Resultsmentioning

confidence: 99%

Modification with Conventional Surfactants to Improve a Lipid-Based Ionic-Liquid-Associated Transcutaneous Anticancer Vaccine

et al. 2023

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Transcutaneous vaccination is one of the successful, affordable, and patient-friendly advanced immunization approaches because of the presence of multiple immune-responsive cell types in the skin. However, in the absence of a preferable facilitator, the skin’s outer layer is a strong impediment to delivering biologically active foreign particles. Lipid-based biocompatible ionic-liquid-mediated nanodrug carriers represent an expedient and distinct strategy to permit transdermal drug delivery; with acceptable surfactants, the performance of drug formulations might be further enhanced. For this purpose, we formulated a lipid-based nanovaccine using a conventional (cationic/anionic/nonionic) surfactant loaded with an antigenic protein and immunomodulator in its core to promote drug delivery by penetrating the skin and boosting drug delivery and immunogenic cell activity. In a follow-up investigation, a freeze–dry emulsification process was used to prepare the nanovaccine, and its transdermal delivery, pharmacokinetic parameters, and ability to activate autoimmune cells in the tumor microenvironment were studied in a tumor-budding C57BL/6N mouse model. These analyses were performed using ELISA, nuclei and HE staining, flow cytometry, and other biological techniques. The immunomodulator-containing nanovaccine significantly (p < 0.001) increased transdermal drug delivery and anticancer immune responses (IgG, IgG1, IgG2, CD8+, CD207+, and CD103+ expression) without causing cellular or biological toxicity. Using a nanovaccination approach, it is possible to create a more targeted and efficient delivery system for cancer antigens, thereby stimulating a stronger immune response compared with conventional aqueous formulations. This might lead to more effective therapeutic and preventative outcomes for patients with cancer.

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“…On the other hand, ROS production derives from a series of ways, and each is influenced by many factors, although the oxidative stress pathway is the main one. 48 In addition, it is reported that unchanged excretion of urinary 8-OH-dG at increased oxidative burden does not rule out the possibilities of a decreased repair capacity and accumulation of 8-OH-dG in DNA. 49,50 To clarify this issue, more research studies should be conducted to obtain more comprehensive and accurate data to improve the understanding.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Urinary Profile of Alkylated DNA Adducts and DNA Oxidative Damage in Sulfur Mustard-Exposed Rats Revealed by Mass Spectrometry Quantification

Wu,

Zhang,

et al. 2023

Chem. Res. Toxicol.

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Alkylation reagents, represented by sulfur mustard (SM), can damage DNA molecules directly as well as lead to oxidative stress, causing DNA lesions indirectly. Correspondingly, two types of biomarkers including alkylated DNA adducts and oxidative DNA adducts are commonly involved in the research of DNA damage evaluation caused by these agents. However, the correlations and differences of the occurrence, duration, severity, and traceability between alkylation and oxidation lesions on the DNA molecular level reflected by these two types of biomarkers have not been systematically studied. A simultaneous determination method for four alkylated DNA adducts, i.e., N7-(2-hydroxyethylthioethyl)2′-guanine (N7-HETEG), O6-(2-hydroxyethylthioethyl)-2′-guanine (O6-HETEG), N3-(2-hydroxyethylthioethyl)-2′-adenine (N3-HETEA), and bis(2-ethyl-N7-guanine)thioether (Bis-G), and the oxidative adduct 8-hydroxy-2′-deoxyguanosine (8-OH-dG) in urine samples by isotope-dilution high-performance liquid chromatography-tandem mass spectrometry (ID-HPLC-MS/MS) was built with a lower limit of detection of 0.02 ng/mL (except Bis-G, 0.05 ng/mL) and a recovery of 79–111%. The profile of these adducts was simultaneously monitored in urine samples after SD rats’ dermal exposure to SM in three dose levels (1, 3, and 10 mg/kg). The time–effect and dose–effect experiments revealed that when exposed to SM, DNA alkylation lesions would happen earlier than those of oxidation. For the two types of biomarkers, alkylated DNA adducts showed an obvious dose–effect relationship and could be used as internal exposure dose and effect biomarkers, while 8-OH-dG did not show a correlation with exposure dose, demonstrating that it was more suitable as a biomarker for DNA oxidative lesions but not an indicator for the extent of cytotoxicity and internal exposure.

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Role of Reactive Oxygen Species in Aging and Age-Related Diseases: A Review

Cited by 61 publications

References 350 publications

Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection throughout aging

Mitochondrial haplotype and mito-nuclear matching drive somatic mutation and selection throughout aging

Modification with Conventional Surfactants to Improve a Lipid-Based Ionic-Liquid-Associated Transcutaneous Anticancer Vaccine

Urinary Profile of Alkylated DNA Adducts and DNA Oxidative Damage in Sulfur Mustard-Exposed Rats Revealed by Mass Spectrometry Quantification

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