Impact of long-term caloric restriction on cardiac senescence

Caloric restriction ameliorates cardiac diastolic dysfunction associated with aging

Ken Shinmura, Kayoko Tamaki, Motoaki Sano, Mitsushige Murata, Hiroyuki Yamakawa, Hideyuki Ishida, Keiichi Fukuda

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Abstract

Approximately half of older patients with congestive heart failure have normal left ventricular (LV) systolic but abnormal LV diastolic function. In mammalian hearts, aging is associated with LV diastolic dysfunction. Caloric restriction (CR) is expected to retard cellular senescence and to attenuate the physiological decline in organ function. Therefore, the aim of the present study was to investigate the impact of long-term CR on cardiac senescence, in particular the effect of CR on LV diastolic dysfunction associated with aging. Male 8-month-old Fischer344 rats were divided into ad libitum fed and CR (40% energy reduction) groups. LV function was evaluated by echocardiography and cardiac senescence was compared between the two groups at the age of 30-month-old. (1) Echocardiography showed similar LV systolic function, but better LV diastolic function in the CR group. (2) Histological analysis revealed that CR attenuated the accumulation of senescence-associated β-galactosidase and lipofuscin and reduced myocyte apoptosis. (3) In measurements of [Ca2+]i transients, the time to 50% relaxation was significantly smaller in the CR group, whereas F/F0 was similar. (4) CR attenuated the decrease in sarcoplasmic reticulum calcium ATPase 2 protein with aging. (5) CR suppressed the mammalian target of rapamycin (mTOR) pathway and increased the ratio of conjugated to cytosolic light chain 3, suggesting that autophagy is enhanced in the CR hearts. In conclusion, CR improves diastolic function in the senescent myocardium by amelioration of the age-associated deterioration in intracellular Ca2+ handling. Enhanced autophagy via the suppression of mTOR during CR may retard cardiac senescence.

Original languageEnglish
Pages (from-to)117-127
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume50
Issue number1
DOIs
Publication statusPublished - 2011 Jan

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Caloric Restriction
Left Ventricular Function
Autophagy
Left Ventricular Dysfunction
Sirolimus
Echocardiography
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Galactosidases
Lipofuscin
Cell Aging
Muscle Cells
Myocardium
Heart Failure
Age Groups

Keywords

  • Aging
  • Autophagy
  • Calcium
  • Cardiac function
  • Nutrition
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Impact of long-term caloric restriction on cardiac senescence: Caloric restriction ameliorates cardiac diastolic dysfunction associated with aging",
abstract = "Approximately half of older patients with congestive heart failure have normal left ventricular (LV) systolic but abnormal LV diastolic function. In mammalian hearts, aging is associated with LV diastolic dysfunction. Caloric restriction (CR) is expected to retard cellular senescence and to attenuate the physiological decline in organ function. Therefore, the aim of the present study was to investigate the impact of long-term CR on cardiac senescence, in particular the effect of CR on LV diastolic dysfunction associated with aging. Male 8-month-old Fischer344 rats were divided into ad libitum fed and CR (40{\%} energy reduction) groups. LV function was evaluated by echocardiography and cardiac senescence was compared between the two groups at the age of 30-month-old. (1) Echocardiography showed similar LV systolic function, but better LV diastolic function in the CR group. (2) Histological analysis revealed that CR attenuated the accumulation of senescence-associated β-galactosidase and lipofuscin and reduced myocyte apoptosis. (3) In measurements of [Ca2+]i transients, the time to 50{\%} relaxation was significantly smaller in the CR group, whereas F/F0 was similar. (4) CR attenuated the decrease in sarcoplasmic reticulum calcium ATPase 2 protein with aging. (5) CR suppressed the mammalian target of rapamycin (mTOR) pathway and increased the ratio of conjugated to cytosolic light chain 3, suggesting that autophagy is enhanced in the CR hearts. In conclusion, CR improves diastolic function in the senescent myocardium by amelioration of the age-associated deterioration in intracellular Ca2+ handling. Enhanced autophagy via the suppression of mTOR during CR may retard cardiac senescence.",
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T2 - Caloric restriction ameliorates cardiac diastolic dysfunction associated with aging

AU - Shinmura, Ken

AU - Tamaki, Kayoko

AU - Sano, Motoaki

AU - Murata, Mitsushige

AU - Yamakawa, Hiroyuki

AU - Ishida, Hideyuki

AU - Fukuda, Keiichi

PY - 2011/1

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N2 - Approximately half of older patients with congestive heart failure have normal left ventricular (LV) systolic but abnormal LV diastolic function. In mammalian hearts, aging is associated with LV diastolic dysfunction. Caloric restriction (CR) is expected to retard cellular senescence and to attenuate the physiological decline in organ function. Therefore, the aim of the present study was to investigate the impact of long-term CR on cardiac senescence, in particular the effect of CR on LV diastolic dysfunction associated with aging. Male 8-month-old Fischer344 rats were divided into ad libitum fed and CR (40% energy reduction) groups. LV function was evaluated by echocardiography and cardiac senescence was compared between the two groups at the age of 30-month-old. (1) Echocardiography showed similar LV systolic function, but better LV diastolic function in the CR group. (2) Histological analysis revealed that CR attenuated the accumulation of senescence-associated β-galactosidase and lipofuscin and reduced myocyte apoptosis. (3) In measurements of [Ca2+]i transients, the time to 50% relaxation was significantly smaller in the CR group, whereas F/F0 was similar. (4) CR attenuated the decrease in sarcoplasmic reticulum calcium ATPase 2 protein with aging. (5) CR suppressed the mammalian target of rapamycin (mTOR) pathway and increased the ratio of conjugated to cytosolic light chain 3, suggesting that autophagy is enhanced in the CR hearts. In conclusion, CR improves diastolic function in the senescent myocardium by amelioration of the age-associated deterioration in intracellular Ca2+ handling. Enhanced autophagy via the suppression of mTOR during CR may retard cardiac senescence.

AB - Approximately half of older patients with congestive heart failure have normal left ventricular (LV) systolic but abnormal LV diastolic function. In mammalian hearts, aging is associated with LV diastolic dysfunction. Caloric restriction (CR) is expected to retard cellular senescence and to attenuate the physiological decline in organ function. Therefore, the aim of the present study was to investigate the impact of long-term CR on cardiac senescence, in particular the effect of CR on LV diastolic dysfunction associated with aging. Male 8-month-old Fischer344 rats were divided into ad libitum fed and CR (40% energy reduction) groups. LV function was evaluated by echocardiography and cardiac senescence was compared between the two groups at the age of 30-month-old. (1) Echocardiography showed similar LV systolic function, but better LV diastolic function in the CR group. (2) Histological analysis revealed that CR attenuated the accumulation of senescence-associated β-galactosidase and lipofuscin and reduced myocyte apoptosis. (3) In measurements of [Ca2+]i transients, the time to 50% relaxation was significantly smaller in the CR group, whereas F/F0 was similar. (4) CR attenuated the decrease in sarcoplasmic reticulum calcium ATPase 2 protein with aging. (5) CR suppressed the mammalian target of rapamycin (mTOR) pathway and increased the ratio of conjugated to cytosolic light chain 3, suggesting that autophagy is enhanced in the CR hearts. In conclusion, CR improves diastolic function in the senescent myocardium by amelioration of the age-associated deterioration in intracellular Ca2+ handling. Enhanced autophagy via the suppression of mTOR during CR may retard cardiac senescence.

KW - Aging

KW - Autophagy

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KW - Nutrition

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