Article

Autophagy in the heart and liver during normal aging and calorie restriction.

Biochemistry of Aging Laboratory, Department of Aging and Geriatric Research, College of Medicine, Institute on Aging, University of Florida, Gainesville, Florida 32610-0107, USA.
Rejuvenation Research (impact factor: 3.83). 10/2007; 10(3):281-92. DOI:10.1089/rej.2006.0535 pp.281-92
Source: PubMed

ABSTRACT Autophagy is a highly regulated intracellular process for the degradation of cellular constituents and essential for the maintenance of a healthy cell. We evaluated the effects of age and life-long calorie restriction on autophagy in heart and liver of young (6 months) and old (26 months) Fisher 344 rats. We observed that the occurrence of autophagic vacuoles was higher in heart than liver. The occurrence of autophagic vacuoles was not affected by age in either tissue, but was increased with calorie restriction in heart but not in liver. Next, we examined the expression of proteins involved in the formation and maturation of autophagosomes (beclin-1, LC3, Atg7, Atg9) or associated with autolysosomes and lysosomes (LAMP-1; cathepsin D). In hearts of both ad libitum-fed and calorie-restricted rats, we observed an increase in expression of beclin-1 and procathepsin D, but not mature cathepsin D, and a decrease in expression of LAMP-1 because of aging. In hearts, calorie restriction stimulated the expression of Atg7 and Atg9 and the lipidation of Atg8 (elevated LC3-II/I ratios) in aged rats. In hearts of ad libitum-fed rats, expression of Atg7 and lipidation of Atg8 were unaffected by age, while the cellular levels of Atg9 were lower in aged animals. Furthermore, we observed that the age- and diet-dependent expression levels of those proteins differed between heart and liver. In conclusion, autophagy in heart and liver did not decrease with age in ad libitum-fed rats, but was enhanced by calorie restriction in the heart. Thus, calorie restriction may mediate some of its beneficial effects by stimulating autophagy in the heart, indicating the potential for cardioprotective therapies.

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Keywords

26 months
 
6 months
 
ad libitum-fed
 
ad libitum-fed rats
 
age-
 
autophagic vacuoles
 
calorie restriction
 
calorie-restricted rats
 
cardioprotective therapies
 
cellular constituents
 
cellular levels
 
degradation
 
diet-dependent expression levels
 
healthy cell
 
hearts
 
life-long calorie restriction
 
mature cathepsin D
 
procathepsin D
 
regulated intracellular process
 
stimulating autophagy