Age-related increases in DNA repair and antioxidant protection

A comparison of the Boyd Orr Cohort of elderly subjects with a younger population sample

Vikki Humphreys, Richard M. Martin, Brian Ratcliffe, Susan Duthie, Sharon Wood, David Gunnell, Andrew R. Collins

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Background One commonly held theory of ageing is that it is caused by oxidative damage to critical molecules in the body, including proteins, lipids and nucleic acids. Accumulation of oxidative DNA damage with age will occur if there is an increase in reactive oxygen species in the body, or a decline in antioxidant defences, or a reduced efficiency of DNA repair.

Subjects and Methods Using the comet assay, we have measured DNA breaks and oxidised purines in lymphocytes from subjects of different age groups: 2035 (n=40), 6370 (n=35), and 7582 (n=22). We also measured the resistance of lymphocyte DNA to H2O2-induced oxidative damage, and the repair activity of cell-free lymphocyte extracts on a substrate containing 8-oxoguanine.

Results We found an increase in oxidative base damage in old age, but this apparently does not result from deterioration of either antioxidant defence or DNA repair. In fact, both of these tend to increase with age. There were few age-related differences in plasma levels of dietary antioxidants: tocopherols and retinol were higher in the older subjects, while lycopene was highest in the youngest age group.

Conclusions It is possible, that in old age, antioxidant defences and DNA repair are induced, in response to a higher level of oxidative damage, as mitochondria become more leaky and release more reactive oxygen. It is equally possible that older people, as survivors, had relatively high levels of antioxidant defences and DNA repair earlier in their lives, compared with those who did not survive to such an age.

Original languageEnglish
Pages (from-to)521-526
Number of pages6
JournalAge and Ageing
Volume36
Issue number5
DOIs
Publication statusPublished - Sep 2007

Keywords

  • DNA damage
  • DNA repair
  • antioxidants
  • Boyd Orr cohort
  • comet assay
  • elderly
  • vitamin-E status
  • nutritional-status
  • damage
  • healthy
  • plasma
  • capacity
  • accumulation
  • glycosylase
  • lymphocytes
  • mutation

Cite this

Age-related increases in DNA repair and antioxidant protection : A comparison of the Boyd Orr Cohort of elderly subjects with a younger population sample. / Humphreys, Vikki; Martin, Richard M.; Ratcliffe, Brian; Duthie, Susan; Wood, Sharon; Gunnell, David; Collins, Andrew R.

In: Age and Ageing, Vol. 36, No. 5, 09.2007, p. 521-526.

Research output: Contribution to journalArticle

Humphreys, Vikki ; Martin, Richard M. ; Ratcliffe, Brian ; Duthie, Susan ; Wood, Sharon ; Gunnell, David ; Collins, Andrew R. / Age-related increases in DNA repair and antioxidant protection : A comparison of the Boyd Orr Cohort of elderly subjects with a younger population sample. In: Age and Ageing. 2007 ; Vol. 36, No. 5. pp. 521-526.
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abstract = "Background One commonly held theory of ageing is that it is caused by oxidative damage to critical molecules in the body, including proteins, lipids and nucleic acids. Accumulation of oxidative DNA damage with age will occur if there is an increase in reactive oxygen species in the body, or a decline in antioxidant defences, or a reduced efficiency of DNA repair. Subjects and Methods Using the comet assay, we have measured DNA breaks and oxidised purines in lymphocytes from subjects of different age groups: 2035 (n=40), 6370 (n=35), and 7582 (n=22). We also measured the resistance of lymphocyte DNA to H2O2-induced oxidative damage, and the repair activity of cell-free lymphocyte extracts on a substrate containing 8-oxoguanine. Results We found an increase in oxidative base damage in old age, but this apparently does not result from deterioration of either antioxidant defence or DNA repair. In fact, both of these tend to increase with age. There were few age-related differences in plasma levels of dietary antioxidants: tocopherols and retinol were higher in the older subjects, while lycopene was highest in the youngest age group. Conclusions It is possible, that in old age, antioxidant defences and DNA repair are induced, in response to a higher level of oxidative damage, as mitochondria become more leaky and release more reactive oxygen. It is equally possible that older people, as survivors, had relatively high levels of antioxidant defences and DNA repair earlier in their lives, compared with those who did not survive to such an age.",
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N2 - Background One commonly held theory of ageing is that it is caused by oxidative damage to critical molecules in the body, including proteins, lipids and nucleic acids. Accumulation of oxidative DNA damage with age will occur if there is an increase in reactive oxygen species in the body, or a decline in antioxidant defences, or a reduced efficiency of DNA repair. Subjects and Methods Using the comet assay, we have measured DNA breaks and oxidised purines in lymphocytes from subjects of different age groups: 2035 (n=40), 6370 (n=35), and 7582 (n=22). We also measured the resistance of lymphocyte DNA to H2O2-induced oxidative damage, and the repair activity of cell-free lymphocyte extracts on a substrate containing 8-oxoguanine. Results We found an increase in oxidative base damage in old age, but this apparently does not result from deterioration of either antioxidant defence or DNA repair. In fact, both of these tend to increase with age. There were few age-related differences in plasma levels of dietary antioxidants: tocopherols and retinol were higher in the older subjects, while lycopene was highest in the youngest age group. Conclusions It is possible, that in old age, antioxidant defences and DNA repair are induced, in response to a higher level of oxidative damage, as mitochondria become more leaky and release more reactive oxygen. It is equally possible that older people, as survivors, had relatively high levels of antioxidant defences and DNA repair earlier in their lives, compared with those who did not survive to such an age.

AB - Background One commonly held theory of ageing is that it is caused by oxidative damage to critical molecules in the body, including proteins, lipids and nucleic acids. Accumulation of oxidative DNA damage with age will occur if there is an increase in reactive oxygen species in the body, or a decline in antioxidant defences, or a reduced efficiency of DNA repair. Subjects and Methods Using the comet assay, we have measured DNA breaks and oxidised purines in lymphocytes from subjects of different age groups: 2035 (n=40), 6370 (n=35), and 7582 (n=22). We also measured the resistance of lymphocyte DNA to H2O2-induced oxidative damage, and the repair activity of cell-free lymphocyte extracts on a substrate containing 8-oxoguanine. Results We found an increase in oxidative base damage in old age, but this apparently does not result from deterioration of either antioxidant defence or DNA repair. In fact, both of these tend to increase with age. There were few age-related differences in plasma levels of dietary antioxidants: tocopherols and retinol were higher in the older subjects, while lycopene was highest in the youngest age group. Conclusions It is possible, that in old age, antioxidant defences and DNA repair are induced, in response to a higher level of oxidative damage, as mitochondria become more leaky and release more reactive oxygen. It is equally possible that older people, as survivors, had relatively high levels of antioxidant defences and DNA repair earlier in their lives, compared with those who did not survive to such an age.

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