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Chronic rapamycin administration maintains mitochondrial protein synthesis in heart and skeletal muscle
Author(s) -
Drake Joshua,
Peelor Frederick F.,
Biela Laurie M.,
Miller Richard A.,
Hamilton Karyn L.,
Miller Benjamin F.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1075.4
Subject(s) - skeletal muscle , longevity , pi3k/akt/mtor pathway , mitochondrion , in vivo , medicine , cytoplasm , biology , endocrinology , microbiology and biotechnology , chemistry , signal transduction , genetics
Suppression of mammalian target of rapamycin (mTOR) signaling with rapamycin increases lifespan. Rapamycin could increase longevity by decreasing global protein synthesis (PS) but this remains to be demonstrated in vivo . A reduction of PS results in energy savings that could be diverted towards somatic maintenance of proteins (e.g. mitochondrial proteins) that promote longevity. Mice fed rapamycin (14 ppm; Rap) for 13.5 weeks were compared to controls (Con). During the last 4 weeks drinking water was supplemented with 8% deuterium oxide (D 2 O). The fraction of new protein was determined by the increase in D 2 O labeled alanine bound to proteins during the labeling period. Skeletal muscle from Rap mice had lower protein synthesis over 4 weeks in mixed (Rap=0.48±0.05, Con=0.55±0.05) and cytoplasmic (cyto) (Rap=0.57±0.03, Con=0.62±0.02) fractions, but not in the mitochondrial (mito) fraction (Rap=0.38±0.04, Con=0.41±0.05). Conversely, no change in synthesis was seen in any fraction of heart muscle (Mixed: Rap=0.65±0.08, Con=0.66±0.05; Cyto: Rap=0.74±0.04, Con=0.76±0.04; Mito: Rap=0.59±0.04, Con=0.63±0.03). The results suggest that Rap diminishes synthesis of cytoplasmic and mixed fraction proteins and maintains mitochondrial proteins in skeletal muscle, but not in heart muscle. Further analysis of tissue specific protein dynamics is likely to give new insights into how rapamycin extends lifespan.