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Caloric restriction prevents age-related decline in skeletal muscle dihydropyridine receptor and ryanodine receptor
1Sticht Center on Aging, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Abstract:
The dihydropyridine receptor (DHPR), a voltage-gated L-type Ca2+ channel, and the Ca2+ release channel/ryanodine receptor isoform-1 (RyR1) are key molecules involved in skeletal muscle excitation-contraction coupling. We have reported age-related decreases in the level of DHPR expression in fast- and slow-twitch muscles from Fisher 344 cross Brown Norway (F344BNX) rats (Renganathan, Messi and Delbono, J. Membr. Biol. 157 (1997) 247-253). Based on these studies we postulate that excitation-contraction uncoupling is a basic mechanism for the decline in muscle force with aging (Delbono, Renganathan and Messi, Muscle Nerve Suppl. 5 (1997) S88-92). In the present study, we extended our studies to older ages and we intended to prevent or retard excitation-contraction uncoupling by restricting the caloric intake of the F344BNX rats from 16 weeks of age. Three age groups, 8-, 18-, and 33-month old caloric restricted rats, were compared with ad libitum fed animals. The number of DHPR and RyR1 and DHPR/RyR1 ratio (an index of the level of receptors uncoupling) in skeletal muscles of 8-month and 18-month rats was not significantly different in either ad libitum fed or caloric restricted rats. However, the age-related decrease in the number of DHPR, RyR1 and DHPR/RyR1 ratio observed in 33-month old ad libitum fed rats was absent in 33-month old caloric restricted rats. These results suggest that caloric restriction prevents age-related decreases in the number of DHPR, RyR1 and DHPR/RyR1 ratio observed in fast- and slow-twitch rat skeletal muscles.
Insights
Caloric restriction in rats prevented age-related declines in key muscle proteins, dihydropyridine receptor (DHPR) and ryanodine receptor 1 (RyR1). This suggests caloric restriction may prevent excitation-contraction uncoupling and muscle weakness in aging skeletal muscle.
Area of Science:
- Physiology
- Aging Research
- Muscle Biology
Background:
- Skeletal muscle excitation-contraction coupling relies on dihydropyridine receptors (DHPR) and ryanodine receptors (RyR1).
- Previous studies showed age-related decreases in DHPR expression, suggesting excitation-contraction uncoupling contributes to age-related muscle force decline.
Purpose of the Study:
- To investigate if caloric restriction can prevent or delay age-related excitation-contraction uncoupling in rat skeletal muscle.
- To examine the effects of caloric restriction on DHPR and RyR1 levels in aging F344BNX rats.
Main Methods:
- Caloric restriction was implemented in F344BNX rats from 16 weeks of age.
- Three age groups (8, 18, and 33 months) of caloric-restricted rats were compared to ad libitum-fed controls.
- The expression levels of DHPR and RyR1, and the DHPR/RyR1 ratio, were quantified in skeletal muscles.
Main Results:
- No significant differences in DHPR, RyR1, or DHPR/RyR1 ratio were observed in 8- and 18-month-old rats between caloric-restricted and ad libitum-fed groups.
- In 33-month-old rats, the age-related decrease in DHPR, RyR1, and the DHPR/RyR1 ratio was absent in the caloric-restricted group.
- Caloric restriction prevented the age-associated decline in these key muscle receptor proteins.
Conclusions:
- Caloric restriction effectively prevents age-related decreases in DHPR and RyR1 levels in rat skeletal muscle.
- These findings support the hypothesis that caloric restriction can mitigate excitation-contraction uncoupling associated with aging.