Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis

Richard M. Reznick; Haihong Zong; Ji Li; Katsutaro Morino; Irene K. Moore; Hannah J. Yu; Zhen Xiang Liu; Jianying Dong; Kirsty J. Mustard; Simon A. Hawley; Douglas Befroy; Marc Pypaert; D. Grahame Hardie; Lawrence H. Young; Gerald I. Shulman

doi:10.1016/j.cmet.2007.01.008

Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis

Richard M. Reznick, Haihong Zong, Ji Li, Katsutaro Morino, Irene K. Moore, Hannah J. Yu, Zhen Xiang Liu, Jianying Dong, Kirsty J. Mustard, Simon A. Hawley, Douglas Befroy, Marc Pypaert, D. Grahame Hardie, Lawrence H. Young, Gerald I. Shulman

Research output: Contribution to journal › Article › peer-review

431 Scopus citations

Abstract

Recent studies have demonstrated a strong relationship between aging-associated reductions in mitochondrial function, dysregulated intracellular lipid metabolism, and insulin resistance. Given the important role of the AMP-activated protein kinase (AMPK) in the regulation of fat oxidation and mitochondrial biogenesis, we examined AMPK activity in young and old rats and found that acute stimulation of AMPK-α₂ activity by 5′-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and exercise was blunted in skeletal muscle of old rats. Furthermore, mitochondrial biogenesis in response to chronic activation of AMPK with β-guanidinopropionic acid (β-GPA) feeding was also diminished in old rats. These results suggest that aging-associated reductions in AMPK activity may be an important contributing factor in the reduced mitochondrial function and dysregulated intracellular lipid metabolism associated with aging.

Original language	English (US)
Pages (from-to)	151-156
Number of pages	6
Journal	Cell metabolism
Volume	5
Issue number	2
DOIs	https://doi.org/10.1016/j.cmet.2007.01.008
State	Published - Feb 7 2007
Externally published	Yes

Keywords

HUMDISEASE

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2007.01.008

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Reznick, R. M., Zong, H., Li, J., Morino, K., Moore, I. K., Yu, H. J., Liu, Z. X., Dong, J., Mustard, K. J., Hawley, S. A., Befroy, D., Pypaert, M., Hardie, D. G., Young, L. H., & Shulman, G. I. (2007). Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis. Cell metabolism, 5(2), 151-156. https://doi.org/10.1016/j.cmet.2007.01.008

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title = "Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis",

abstract = "Recent studies have demonstrated a strong relationship between aging-associated reductions in mitochondrial function, dysregulated intracellular lipid metabolism, and insulin resistance. Given the important role of the AMP-activated protein kinase (AMPK) in the regulation of fat oxidation and mitochondrial biogenesis, we examined AMPK activity in young and old rats and found that acute stimulation of AMPK-α2 activity by 5′-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and exercise was blunted in skeletal muscle of old rats. Furthermore, mitochondrial biogenesis in response to chronic activation of AMPK with β-guanidinopropionic acid (β-GPA) feeding was also diminished in old rats. These results suggest that aging-associated reductions in AMPK activity may be an important contributing factor in the reduced mitochondrial function and dysregulated intracellular lipid metabolism associated with aging.",

keywords = "HUMDISEASE",

author = "Reznick, {Richard M.} and Haihong Zong and Ji Li and Katsutaro Morino and Moore, {Irene K.} and Yu, {Hannah J.} and Liu, {Zhen Xiang} and Jianying Dong and Mustard, {Kirsty J.} and Hawley, {Simon A.} and Douglas Befroy and Marc Pypaert and Hardie, {D. Grahame} and Young, {Lawrence H.} and Shulman, {Gerald I.}",

note = "Funding Information: We thank Christina Horensavitz for her expertise with electron microscopy. This work was supported by grants P30 DK-45735, R01 DK-40936, U24 DK-59635, R01 HL-63811, and T32 GM-07499 from the US Public Health Service. G.I.S. is the recipient of a Distinguished Clinical Scientist Award from the American Diabetes Association. K.J.M., S.A.H., and D.G.H. are supported by a Programme Grant from the Wellcome Trust (UK) and the EXGENESIS integrated project (LSHM-CT-2004-005272) of the European Commission. ",

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doi = "10.1016/j.cmet.2007.01.008",

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AU - Reznick, Richard M.

AU - Zong, Haihong

AU - Li, Ji

AU - Morino, Katsutaro

AU - Moore, Irene K.

AU - Yu, Hannah J.

AU - Liu, Zhen Xiang

AU - Dong, Jianying

AU - Mustard, Kirsty J.

AU - Hawley, Simon A.

AU - Befroy, Douglas

AU - Pypaert, Marc

AU - Hardie, D. Grahame

AU - Young, Lawrence H.

AU - Shulman, Gerald I.

N1 - Funding Information: We thank Christina Horensavitz for her expertise with electron microscopy. This work was supported by grants P30 DK-45735, R01 DK-40936, U24 DK-59635, R01 HL-63811, and T32 GM-07499 from the US Public Health Service. G.I.S. is the recipient of a Distinguished Clinical Scientist Award from the American Diabetes Association. K.J.M., S.A.H., and D.G.H. are supported by a Programme Grant from the Wellcome Trust (UK) and the EXGENESIS integrated project (LSHM-CT-2004-005272) of the European Commission.

PY - 2007/2/7

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N2 - Recent studies have demonstrated a strong relationship between aging-associated reductions in mitochondrial function, dysregulated intracellular lipid metabolism, and insulin resistance. Given the important role of the AMP-activated protein kinase (AMPK) in the regulation of fat oxidation and mitochondrial biogenesis, we examined AMPK activity in young and old rats and found that acute stimulation of AMPK-α2 activity by 5′-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and exercise was blunted in skeletal muscle of old rats. Furthermore, mitochondrial biogenesis in response to chronic activation of AMPK with β-guanidinopropionic acid (β-GPA) feeding was also diminished in old rats. These results suggest that aging-associated reductions in AMPK activity may be an important contributing factor in the reduced mitochondrial function and dysregulated intracellular lipid metabolism associated with aging.

AB - Recent studies have demonstrated a strong relationship between aging-associated reductions in mitochondrial function, dysregulated intracellular lipid metabolism, and insulin resistance. Given the important role of the AMP-activated protein kinase (AMPK) in the regulation of fat oxidation and mitochondrial biogenesis, we examined AMPK activity in young and old rats and found that acute stimulation of AMPK-α2 activity by 5′-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and exercise was blunted in skeletal muscle of old rats. Furthermore, mitochondrial biogenesis in response to chronic activation of AMPK with β-guanidinopropionic acid (β-GPA) feeding was also diminished in old rats. These results suggest that aging-associated reductions in AMPK activity may be an important contributing factor in the reduced mitochondrial function and dysregulated intracellular lipid metabolism associated with aging.

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Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis

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Keywords

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