Calorie Restriction Facilitates Aging‐Related Muscle Loss in the Aged Mice

• Published in: The FASEB journal 2017-04, Vol.31 (S1)
• Main Authors: Park, Sung Eun, Chung, Hae Young, Park, Yoon Jung
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.31.1_supplement.lb306

Abstract only Aging‐related muscle loss is one of the common health problems in the elderly people and is associated with various aging‐related diseases. One of major factors for the muscle loss is dietary intake. Multiple studies have reported positive effects of calorie restriction (CR) on expansion of longevity and prevention of aging‐related diseases since the McCay report (1935). However, CR in the elderly may not have the positive effects due to their different physiological condition. In this study, we investigated whether CR in the old mice had an impact on the aging‐related muscle loss. Skeletal muscle tissues were obtained from male SD rats aged 6 and 25 months (n=10) with or without a short‐term (4 weeks) CR just before the sacrifice. Total mRNAs were isolated and were used for a genome‐wide expression analysis using microarray to examine molecular patterns of muscle structuring and degradation as well as glucose metabolic pathway, which were identified as aging‐related molecular signature of sarcopenia in a publically available human data set (Giresi PG, 2005) by the secondary analysis. As results, a marker for muscle structuring MyH4 was downregulated in the aged group under short‐term CR but MuRF1, a muscle degradation marker, showed dramatic increase under same circumstance. Hk2 and Prkaa1 were decreased in the young group under CR, however the effect of diet showed no significant difference in the aged group. Il6st, a gene which is known to be hypomethylated and upregulated with aging, was increased at 25 months in the CR group but showed no significant difference in normal diet group, and Mthfr, was downregulated under same condition. Based on the results above, the short‐term CR in the aged mice accelerates muscle degradation with decreased MyH4 and increased MuRF1 mRNA level, and cellular nutrition sensor is desensitized compared to young group. Furthermore, upregulated Il6st and downregulated Mthfr in aged group with CR compared to young group with CR implies methylation pattern change may be affected not only by aging but also nutritional stress. In summary, distinct transcriptional patterns towards muscle degradation, metabolic pathways, and methylation revealed that CR facilitates aging‐related muscle loss, rather than lowing the risk of metabolic stress, when applied to the aged group.