Dietary restriction increases protein acetylation in the livers of aged rats

Akihiro Nakamura, Kyojiro Kawakami, Fuyuki Kametani, Sataro Goto

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Dietary restriction (DR) is a well-established biological method for lifespan extension in various organisms by delaying the progression of age-related disorders. With regard to its molecular mechanisms, a family of NAD-dependent protein deacetylases, such as sirtuins, is considered to mediate DR-induced lifespan extension in some lower organisms. Furthermore, the effects of DR on sirtuins (e.g. SIRT1, SIRT2, SIRT3, and SIRT5) have also been reported in mammals. However, the relationship between sirtuins and DR-associated longevity in mammals is still not clear. In addition, ageing and DR-associated changes in cellular protein acetylation have not been fully elucidated, especially in DR-aged animals. Objective: We aimed to elucidate the effect of ageing and DR on cellular protein acetylation in young and aged rats. Methods: Fischer 344 rats were subjected to DR for 7.5 or 25.5 months from 1.5 months of age. Protein acetylation status in tissues was analyzed by Western blotting, subcellular fractionation, and immuno-pull-down assay. We also analyzed the quantitative changes in some related deacetylases and an acetyltransferase. Results: Acetylation of multiple proteins in the liver of young and aged rats decreased slightly with ageing and increased markedly under DR. The results of subcellular fractionation revealed that the DR-induced increase in protein acetylation was more prominent in extranuclear proteins than in nuclear proteins, indicating that acetylation is global, but protein-specific. This was further confirmed in the results of immune-pull-down assays for mitochondrial acetylated proteins. Cellular protein acetylation is regulated by multiple factors, including various deacetylases and acetyltransferases. With regard to the possible mechanisms of DR-induced increases in protein acetylation, we observed that DR increased SIRT3 expression in the liver of young and aged rats. Expression of the mitochondrial protein acetyltransferase GCN5L1 significantly increased with ageing but did not respond to DR. Conclusions: The increased acetylation of extranuclear proteins may be involved in DR-induced anti-ageing effects including longevity. However, the mechanisms underlying the changes in protein acetylation might not result from quantitative changes in mitochondrial sirtuins and the mitochondrial protein acetyltransferase.

Original languageEnglish
Pages (from-to)542-548
Number of pages7
JournalGerontology
Volume59
Issue number6
DOIs
Publication statusPublished - Oct 2013

Fingerprint

Acetylation
Liver
Sirtuins
Proteins
Acetyltransferases
Mitochondrial Proteins
Mammals
Inbred F344 Rats
Nuclear Proteins
NAD
Western Blotting

Keywords

  • Acetylation
  • Ageing
  • Dietary restriction
  • Fischer 344 rats

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

Cite this

Dietary restriction increases protein acetylation in the livers of aged rats. / Nakamura, Akihiro; Kawakami, Kyojiro; Kametani, Fuyuki; Goto, Sataro.

In: Gerontology, Vol. 59, No. 6, 10.2013, p. 542-548.

Research output: Contribution to journalArticle

Nakamura, Akihiro ; Kawakami, Kyojiro ; Kametani, Fuyuki ; Goto, Sataro. / Dietary restriction increases protein acetylation in the livers of aged rats. In: Gerontology. 2013 ; Vol. 59, No. 6. pp. 542-548.
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N2 - Background: Dietary restriction (DR) is a well-established biological method for lifespan extension in various organisms by delaying the progression of age-related disorders. With regard to its molecular mechanisms, a family of NAD-dependent protein deacetylases, such as sirtuins, is considered to mediate DR-induced lifespan extension in some lower organisms. Furthermore, the effects of DR on sirtuins (e.g. SIRT1, SIRT2, SIRT3, and SIRT5) have also been reported in mammals. However, the relationship between sirtuins and DR-associated longevity in mammals is still not clear. In addition, ageing and DR-associated changes in cellular protein acetylation have not been fully elucidated, especially in DR-aged animals. Objective: We aimed to elucidate the effect of ageing and DR on cellular protein acetylation in young and aged rats. Methods: Fischer 344 rats were subjected to DR for 7.5 or 25.5 months from 1.5 months of age. Protein acetylation status in tissues was analyzed by Western blotting, subcellular fractionation, and immuno-pull-down assay. We also analyzed the quantitative changes in some related deacetylases and an acetyltransferase. Results: Acetylation of multiple proteins in the liver of young and aged rats decreased slightly with ageing and increased markedly under DR. The results of subcellular fractionation revealed that the DR-induced increase in protein acetylation was more prominent in extranuclear proteins than in nuclear proteins, indicating that acetylation is global, but protein-specific. This was further confirmed in the results of immune-pull-down assays for mitochondrial acetylated proteins. Cellular protein acetylation is regulated by multiple factors, including various deacetylases and acetyltransferases. With regard to the possible mechanisms of DR-induced increases in protein acetylation, we observed that DR increased SIRT3 expression in the liver of young and aged rats. Expression of the mitochondrial protein acetyltransferase GCN5L1 significantly increased with ageing but did not respond to DR. Conclusions: The increased acetylation of extranuclear proteins may be involved in DR-induced anti-ageing effects including longevity. However, the mechanisms underlying the changes in protein acetylation might not result from quantitative changes in mitochondrial sirtuins and the mitochondrial protein acetyltransferase.

AB - Background: Dietary restriction (DR) is a well-established biological method for lifespan extension in various organisms by delaying the progression of age-related disorders. With regard to its molecular mechanisms, a family of NAD-dependent protein deacetylases, such as sirtuins, is considered to mediate DR-induced lifespan extension in some lower organisms. Furthermore, the effects of DR on sirtuins (e.g. SIRT1, SIRT2, SIRT3, and SIRT5) have also been reported in mammals. However, the relationship between sirtuins and DR-associated longevity in mammals is still not clear. In addition, ageing and DR-associated changes in cellular protein acetylation have not been fully elucidated, especially in DR-aged animals. Objective: We aimed to elucidate the effect of ageing and DR on cellular protein acetylation in young and aged rats. Methods: Fischer 344 rats were subjected to DR for 7.5 or 25.5 months from 1.5 months of age. Protein acetylation status in tissues was analyzed by Western blotting, subcellular fractionation, and immuno-pull-down assay. We also analyzed the quantitative changes in some related deacetylases and an acetyltransferase. Results: Acetylation of multiple proteins in the liver of young and aged rats decreased slightly with ageing and increased markedly under DR. The results of subcellular fractionation revealed that the DR-induced increase in protein acetylation was more prominent in extranuclear proteins than in nuclear proteins, indicating that acetylation is global, but protein-specific. This was further confirmed in the results of immune-pull-down assays for mitochondrial acetylated proteins. Cellular protein acetylation is regulated by multiple factors, including various deacetylases and acetyltransferases. With regard to the possible mechanisms of DR-induced increases in protein acetylation, we observed that DR increased SIRT3 expression in the liver of young and aged rats. Expression of the mitochondrial protein acetyltransferase GCN5L1 significantly increased with ageing but did not respond to DR. Conclusions: The increased acetylation of extranuclear proteins may be involved in DR-induced anti-ageing effects including longevity. However, the mechanisms underlying the changes in protein acetylation might not result from quantitative changes in mitochondrial sirtuins and the mitochondrial protein acetyltransferase.

KW - Acetylation

KW - Ageing

KW - Dietary restriction

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