Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle

James N. Cobley, George K. Sakellariou, Scott Murray, Sarah Waldron, Warren Gregson, Jatin G. Burniston, James P. Morton, Lesley A. Iwanejko, Graeme L. Close

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Abstract

Background
The aim of the present study was to determine the influence of age and habitual activity level, at rest and following a single bout of high-intensity exercise, on the levels of three proteins poly(ADP-ribose) polymerase-1 (PARP-1), cleaved-PARP-1 and poly(ADP-ribose) glycohydrolase (PARG), involved in the DNA repair and cell death responses to stress and genotoxic insults. Muscle biopsies were obtained from the vastus lateralis of young trained (22 ± 3 years, n = 6), young untrained (24 ± 4 years, n = 6), old trained (64 ± 3 years, n = 6) and old untrained (65 ± 6 years, n = 6) healthy males before, immediately after and three days following a high-intensity interval exercise bout.

Results
PARP-1, which catalyzes poly(ADP-ribosyl)ation of proteins and DNA in response to a range of intrinsic and extrinsic stresses, was increased at baseline in old trained and old untrained compared with young trained and young untrained participants (P ≤ 0.05). Following exercise, PARP-1 levels remained unchanged in young trained participants, in contrast to old trained and old untrained where levels decreased and young untrained where levels increased (P ≤ 0.05). Interestingly, baseline levels of the cleaved PARP-1, a marker of apoptosis, and PARG, responsible for polymer degradation, were both significantly elevated in old untrained compared with old trained, young trained and young untrained (P ≤ 0.05). Despite this baseline difference in PARG, there was no change in any group following exercise. There was a non-significant statistical trend (P = 0.072) towards increased cleaved-PARP-1 expression post-exercise in younger but not old persons, regardless of training status.

Conclusions
Collectively, these results show that exercise slows the progression towards a chronically stressed state but has no impact on the age-related attenuated response to acute exercise. Our findings provide valuable insight into how habitual exercise training could protect skeletal muscle from chronic damage to macromolecules and may reduce sarcopenia in older people.
Original languageEnglish
Article number11
Number of pages8
JournalLongevity & Healthspan
Volume2
DOIs
Publication statusPublished - 12 Jul 2013

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DNA Damage
Skeletal Muscle
Exercise
Sarcopenia
Quadriceps Muscle
DNA Repair
Polymers
Cell Death
Poly (ADP-Ribose) Polymerase-1
Apoptosis
Biopsy
Muscles
DNA
poly ADP-ribose glycohydrolase
Proteins

Cite this

Cobley, J. N., Sakellariou, G. K., Murray, S., Waldron, S., Gregson, W., Burniston, J. G., ... Close, G. L. (2013). Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle. Longevity & Healthspan, 2, [11]. https://doi.org/10.1186/2046-2395-2-11
Cobley, James N. ; Sakellariou, George K. ; Murray, Scott ; Waldron, Sarah ; Gregson, Warren ; Burniston, Jatin G. ; Morton, James P. ; Iwanejko, Lesley A. ; Close, Graeme L. / Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle. In: Longevity & Healthspan. 2013 ; Vol. 2.
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abstract = "BackgroundThe aim of the present study was to determine the influence of age and habitual activity level, at rest and following a single bout of high-intensity exercise, on the levels of three proteins poly(ADP-ribose) polymerase-1 (PARP-1), cleaved-PARP-1 and poly(ADP-ribose) glycohydrolase (PARG), involved in the DNA repair and cell death responses to stress and genotoxic insults. Muscle biopsies were obtained from the vastus lateralis of young trained (22 ± 3 years, n = 6), young untrained (24 ± 4 years, n = 6), old trained (64 ± 3 years, n = 6) and old untrained (65 ± 6 years, n = 6) healthy males before, immediately after and three days following a high-intensity interval exercise bout.ResultsPARP-1, which catalyzes poly(ADP-ribosyl)ation of proteins and DNA in response to a range of intrinsic and extrinsic stresses, was increased at baseline in old trained and old untrained compared with young trained and young untrained participants (P ≤ 0.05). Following exercise, PARP-1 levels remained unchanged in young trained participants, in contrast to old trained and old untrained where levels decreased and young untrained where levels increased (P ≤ 0.05). Interestingly, baseline levels of the cleaved PARP-1, a marker of apoptosis, and PARG, responsible for polymer degradation, were both significantly elevated in old untrained compared with old trained, young trained and young untrained (P ≤ 0.05). Despite this baseline difference in PARG, there was no change in any group following exercise. There was a non-significant statistical trend (P = 0.072) towards increased cleaved-PARP-1 expression post-exercise in younger but not old persons, regardless of training status.ConclusionsCollectively, these results show that exercise slows the progression towards a chronically stressed state but has no impact on the age-related attenuated response to acute exercise. Our findings provide valuable insight into how habitual exercise training could protect skeletal muscle from chronic damage to macromolecules and may reduce sarcopenia in older people.",
author = "Cobley, {James N.} and Sakellariou, {George K.} and Scott Murray and Sarah Waldron and Warren Gregson and Burniston, {Jatin G.} and Morton, {James P.} and Iwanejko, {Lesley A.} and Close, {Graeme L.}",
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Cobley, JN, Sakellariou, GK, Murray, S, Waldron, S, Gregson, W, Burniston, JG, Morton, JP, Iwanejko, LA & Close, GL 2013, 'Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle', Longevity & Healthspan, vol. 2, 11. https://doi.org/10.1186/2046-2395-2-11

Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle. / Cobley, James N.; Sakellariou, George K.; Murray, Scott; Waldron, Sarah; Gregson, Warren; Burniston, Jatin G.; Morton, James P.; Iwanejko, Lesley A.; Close, Graeme L.

In: Longevity & Healthspan, Vol. 2, 11, 12.07.2013.

Research output: Contribution to journalArticle

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T1 - Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle

AU - Cobley, James N.

AU - Sakellariou, George K.

AU - Murray, Scott

AU - Waldron, Sarah

AU - Gregson, Warren

AU - Burniston, Jatin G.

AU - Morton, James P.

AU - Iwanejko, Lesley A.

AU - Close, Graeme L.

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N2 - BackgroundThe aim of the present study was to determine the influence of age and habitual activity level, at rest and following a single bout of high-intensity exercise, on the levels of three proteins poly(ADP-ribose) polymerase-1 (PARP-1), cleaved-PARP-1 and poly(ADP-ribose) glycohydrolase (PARG), involved in the DNA repair and cell death responses to stress and genotoxic insults. Muscle biopsies were obtained from the vastus lateralis of young trained (22 ± 3 years, n = 6), young untrained (24 ± 4 years, n = 6), old trained (64 ± 3 years, n = 6) and old untrained (65 ± 6 years, n = 6) healthy males before, immediately after and three days following a high-intensity interval exercise bout.ResultsPARP-1, which catalyzes poly(ADP-ribosyl)ation of proteins and DNA in response to a range of intrinsic and extrinsic stresses, was increased at baseline in old trained and old untrained compared with young trained and young untrained participants (P ≤ 0.05). Following exercise, PARP-1 levels remained unchanged in young trained participants, in contrast to old trained and old untrained where levels decreased and young untrained where levels increased (P ≤ 0.05). Interestingly, baseline levels of the cleaved PARP-1, a marker of apoptosis, and PARG, responsible for polymer degradation, were both significantly elevated in old untrained compared with old trained, young trained and young untrained (P ≤ 0.05). Despite this baseline difference in PARG, there was no change in any group following exercise. There was a non-significant statistical trend (P = 0.072) towards increased cleaved-PARP-1 expression post-exercise in younger but not old persons, regardless of training status.ConclusionsCollectively, these results show that exercise slows the progression towards a chronically stressed state but has no impact on the age-related attenuated response to acute exercise. Our findings provide valuable insight into how habitual exercise training could protect skeletal muscle from chronic damage to macromolecules and may reduce sarcopenia in older people.

AB - BackgroundThe aim of the present study was to determine the influence of age and habitual activity level, at rest and following a single bout of high-intensity exercise, on the levels of three proteins poly(ADP-ribose) polymerase-1 (PARP-1), cleaved-PARP-1 and poly(ADP-ribose) glycohydrolase (PARG), involved in the DNA repair and cell death responses to stress and genotoxic insults. Muscle biopsies were obtained from the vastus lateralis of young trained (22 ± 3 years, n = 6), young untrained (24 ± 4 years, n = 6), old trained (64 ± 3 years, n = 6) and old untrained (65 ± 6 years, n = 6) healthy males before, immediately after and three days following a high-intensity interval exercise bout.ResultsPARP-1, which catalyzes poly(ADP-ribosyl)ation of proteins and DNA in response to a range of intrinsic and extrinsic stresses, was increased at baseline in old trained and old untrained compared with young trained and young untrained participants (P ≤ 0.05). Following exercise, PARP-1 levels remained unchanged in young trained participants, in contrast to old trained and old untrained where levels decreased and young untrained where levels increased (P ≤ 0.05). Interestingly, baseline levels of the cleaved PARP-1, a marker of apoptosis, and PARG, responsible for polymer degradation, were both significantly elevated in old untrained compared with old trained, young trained and young untrained (P ≤ 0.05). Despite this baseline difference in PARG, there was no change in any group following exercise. There was a non-significant statistical trend (P = 0.072) towards increased cleaved-PARP-1 expression post-exercise in younger but not old persons, regardless of training status.ConclusionsCollectively, these results show that exercise slows the progression towards a chronically stressed state but has no impact on the age-related attenuated response to acute exercise. Our findings provide valuable insight into how habitual exercise training could protect skeletal muscle from chronic damage to macromolecules and may reduce sarcopenia in older people.

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DO - 10.1186/2046-2395-2-11

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Cobley JN, Sakellariou GK, Murray S, Waldron S, Gregson W, Burniston JG et al. Lifelong endurance training attenuates age-related genotoxic stress in human skeletal muscle. Longevity & Healthspan. 2013 Jul 12;2. 11. https://doi.org/10.1186/2046-2395-2-11