DNA status in brain and heart as prominent co-determinant for life span? Assessing the different degrees of DNA damage, damage susceptibility, and repair capability in different organs of young and old mice

Ζahn, Rudolf K.; Jaud, Susanne; Schröder, Heinz C.; Zahn-Daimler, Gertrud

doi:10.1016/0047-6374(96)01738-1

Cited by 16 publications

(5 citation statements)

References 33 publications

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“…À and H 2 O 2 ) and DNA damage (measured in the form of nmol MDA equivalents/mg DNA) in the older over the younger participants (Table 2) (5) in the present study indicates that the old people were more susceptible to oxidative stress (41), and our results are consistent with the general definition of aging as the progressive accumulation of changes responsible for the decreased ability of the organism to maintain the homeostatic balance (1,7,31,(42)(43)(44)(45).…”

Section: Discussionsupporting

confidence: 89%

Age-Related Correlation Between Antioxidant Enzymes and DNA Damage With Smoking and Body Mass Index

Thavanati

Kanala²,

Dios³

et al. 2008

The Journals of Gerontology Series A: Biological Sciences and M

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To understand whether oxidants contribute to the initiation and/or promulgation toward aging, the present study has been undertaken on 220 healthy male volunteers aged 20-80 years selected from the defined electoral area (suburbs of Tirupati, Andhra Pradesh, India) to evaluate the concentrations of free radicals (superoxide anion, hydrogen peroxide), lymphocyte antioxidant enzymes (glutathione S-transferase, superoxide dismutase, catalase), and DNA damage in relation to obesity and smoking (lifestyles). A two fold increase of lymphocyte free radical generation (DNA damage) was observed in older age groups with a reduced antioxidant potential, forming a link between cigarette smoking and oxidative stress represented by an antioxidant imbalance. Body mass index had a positive relationship with oxidative stress, but antioxidant levels did not vary with body mass index. The findings conclude that free radical-mediated oxidative stress and DNA damage accelerate with lifestyle variations under reduced antioxidant potential.

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Section: Discussionsupporting

confidence: 89%

Age-Related Correlation Between Antioxidant Enzymes and DNA Damage With Smoking and Body Mass Index

Thavanati

Kanala²,

Dios³

et al. 2008

The Journals of Gerontology Series A: Biological Sciences and M

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“…The mitochondrial OGG1 activity, however, was relatively lower in heart and muscle as well as in brain. Because heart and brain are postmitotic tissues, it has been postulated that accumulation of DNA damage in these tissues is a critical determinant for life span (33). Higher levels of 8‐oxodG were detected in rat brains than other tissues such as kidney and lung (34), and these have been shown to increase significantly with age in heart and brain (18).…”

Section: Discussionmentioning

confidence: 99%

Base excision repair capacity in mitochondria and nuclei: tissue‐specific variations

et al. 2002

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Base excision repair is the main pathway for repair of oxidative base lesions in DNA. Mammalian cells must maintain genomic stability in their nuclear and mitochondrial genomes, which have different degrees of vulnerability to DNA damage. This study quantifies DNA glycosylase activity in mitochondria and nucleus from C57/BL 6 mouse tissues including brain, liver, heart, muscle, kidney, and testis. The activities of oxoguanine DNA glycosylase (OGG1), uracil DNA glycosylase, and endonuclease III homologue 1 (NTH1) were measured using oligonucleotide substrates with DNA lesions specific for each glycosylase. Mitochondrial content was normalized to citrate synthase activity and mitochondrial function was assessed by measuring cytochrome c oxidase (COX) activity. In nuclear and mitochondrial extracts, the highest DNA glycosylase activities were in testis. Brain and heart, tissues with the highest oxidative load, did not have higher levels of OGG1 or NTH1 activity than muscle or kidney, which are more glycolytic tissues. In general, mitochondrial extracts have lower DNA glycosylase activity than nuclear extracts. There was no correlation between glycosylase activities in the mitochondrial extracts and COX activity, suggesting that DNA repair enzymes may be regulated by a mechanism different from this mitochondrial enzyme.

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“…Other investigators have also observed that cells or tissues from old animals are more sensitive to oxidative stress in vitro than cells or tissues from young animals. For example, Zahn et al (37) reported that DNA damage (strand breaks) induced after incubating tissues (liver, heart, brain, kidney, lung, skeletal muscle, and intestine) with nitroquinolin-N-oxide in vitro was 2-fold greater for tissues from old mice compared with tissues from young mice. Guo et al (36) found that more DNA damage (cyclobutane pyrimidine dimers) was induced by UV-irradiation in the nDNA of primary cultures of hepatocytes isolated from old rats compared with hepatocytes isolated from young rats.…”

Section: Discussionmentioning

confidence: 99%

Does oxidative damage to DNA increase with age?

Hamilton

Remmen

Drake

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

700

426

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The levels of 8-oxo-2-deoxyguanosine (oxo8dG) in DNA isolated from tissues of rodents (male F344 rats, male B6D2F1 mice, male C57BL͞6 mice, and female C57BL͞6 mice) of various ages were measured using sodium iodide to prevent oxidative damage to DNA during DNA isolation. Oxo8dG was measured in nuclear DNA (nDNA) isolated from liver, heart, brain, kidney, skeletal muscle, and spleen and in mitochondrial DNA (mtDNA) isolated from liver. We observed a significant increase in oxo8dG levels in nDNA with age in all tissues and strains of rodents studied. The age-related increase in oxo8dG in nDNA from old mice was shown not to the result of the tissue's reduced ability to remove the oxo8dG lesion. Rather, the increase in oxo8dG levels appears to arise from an age-related increase in the sensitivity of these tissues to oxidative stress. We also observed an age-related increase in oxo8dG in mtDNA isolated from the livers of the rats and mice. Dietary restriction, which is known to retard aging and increase the lifespan of rodents, was shown to significantly reduce the agerelated accumulation of oxo8dG levels in nDNA in all tissues of male B6D23F1 mice and in most tissues of male F344 rats. Our study also showed that dietary restriction prevented the age-related increase in oxo8dG levels in mtDNA isolated from the livers of both rats and mice. T he oxidative stress hypothesis of aging (or the free radical hypothesis as it was first proposed) is currently one of the most popular explanations for how aging occurs at the biochemical level. The basic tenet of the oxidative stress hypothesis is that the age-related loss of physiological function and aging are because of the progressive and irreversible accumulation of oxidative damage (1). Over the past decade, the oxidative stress hypothesis of aging has gained wide acceptance because numerous studies have shown a strong correlation between increasing age and the accumulation of oxidative damage to cellular macromolecules (2, 3) and because the increased survival observed with dietary restriction has been correlated to reduced oxidative damage (3,4). It also appears that certain types of pathological lesions that arise with age are associated with increased levels of oxidative damage to cellular macromolecules (5, 6).In 1990, Ames' laboratory reported the first data on the effect of aging on DNA oxidation (7). They observed a significant (Ϸ2-fold) increase in 8-oxo-2-deoxyguanosine (oxo8dG) levels in nuclear DNA (nDNA) isolated from liver, kidney, and intestine of male rats between 2 and 24 months of age. Later, Ames et al. (5) reported that the levels of oxo8dG in mitochondrial DNA (mtDNA) isolated from male rat liver increased 2-to 3-fold with age. Since 1990, a number of research groups have observed an age-related increase in the level of oxo8dG in both nDNA and mtDNA in a variety of tissues of rats and mice (8).On the other hand, many investigators have been unable to detect a significant increase in DNA oxidation in rodent tissues with increasing age (9). The most lik...

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DNA status in brain and heart as prominent co-determinant for life span? Assessing the different degrees of DNA damage, damage susceptibility, and repair capability in different organs of young and old mice

Cited by 16 publications

References 33 publications

Age-Related Correlation Between Antioxidant Enzymes and DNA Damage With Smoking and Body Mass Index

Age-Related Correlation Between Antioxidant Enzymes and DNA Damage With Smoking and Body Mass Index

Base excision repair capacity in mitochondria and nuclei: tissue‐specific variations

Does oxidative damage to DNA increase with age?

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