Life long calorie restriction increases heat shock proteins and proteasome activity in soleus muscles of Fisher 344 rats.
Heat shock proteins (HSP's) closely interact with 20S proteasome and have been shown to maintain catalytic activity, responsible for the prevention of protein aggregation. A decrease in both proteasome activity and heat shock proteins (HSP's) has been observed with age. We investigated whether life-long calorie restriction (CR), a natural intervention, which prolongs life span, could prevent the age-associated decline in HSP's and restore the proteolytic activity of the 20S proteasome in skeletal muscle. Hence, we investigated HSP's and proteasome activity in the soleus muscle from 12-mo-old (Adult) and 26-28 mo old ad libitum fed (Old), and 26-28 mo old CR (Old-CR; fed 40% of ad libitum for their lifespan) male Fisher 344 rats. Trypsin-like proteasome activity in Old rats was significantly less than both Adult and Old-CR rats. Furthermore, no significant changes where found in chymotrypsin-like proteasome activity due to age or diet. Levels of HSP 72 and 25 were significantly less in Old animals when compared to both Adult and Old-CR rats. In contrast, HSP 90 was elevated in Old rats by 220% compared to adult animals and life-long calorie restriction caused a significant induction (150%) compared to age-matched ad libitum fed animals. Protein carbonyls were significantly elevated in Old when compared to Adult rats, but showed no significant decline due to life long CR. This study shows that HSP's may be largely responsible for the restoration of the trypsin-like activity of the 20S proteasome with age. The large increase in HSP 90 is intriguing and further studies are required to elucidate its role in maintaining 20S proteasome function.
Selsby
Joshua T
JT
Muscle Physiology Laboratory, Department of Applied Physiology and Kinesiology, University of Florida, P.O. Box 118205, Gainesville, FL 32611, USA.
Judge
Andrew R
AR
Yimlamai
Tossaporn
T
Leeuwenburgh
Christiaan
C
Dodd
Stephen L
SL
D000818:Animals; D031204:Caloric Restriction; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D046988:Proteasome Endopeptidase Complex