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Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction.
FASEB J. 2005 Apr; 19(6):668-70.FJ

Abstract

Increased tumor necrosis factor-alpha (TNF-alpha) levels have been found with age and are connected to muscle atrophy and cell loss, yet the signaling events that occur in vivo are unknown. Calorie restriction (CR), a robust intervention shown to repeatedly evade the physiological declines associated with aging, has been reported to reduce TNF-alpha and may assist in understanding the mechanisms of muscle sarcopenia. The effects of age and CR on muscle mass, myocyte area, fiber number, myocyte TNF-alpha expression, plasma TNF-alpha levels, and specific elements linked with the TNF-alpha signaling cascade (TNF-R1, IKKgamma, IkappaBalpha, p65, NF-kappaB binding activity, FADD, caspase-8, and DNA fragmentation) were investigated in soleus (predominately Type I fiber), and superficial vastus lateralis (SVL, predominately Type II fiber), of 6-month-old ad libitum fed (6AL), 26-month-old ad libitum fed (26AL), and 26-month-old calorie-restricted (26CR) male Fischer 344 rats (CR = 40% restriction compared with ad libitum). Plasma TNF-alpha was increased with age, and the age-associated rise was attenuated with life-long CR. In soleus muscle, we reported a greater capacity to cultivate inflammatory signaling through the transcription factor NF-kappaB compared with that detected in SVL with age. In contrast, in the SVL TNF-alpha stimulated apoptotic signaling with age to a much higher extent than was observed in the soleus. Moreover, a reduction in muscle mass, cross-sectional area, and fiber number in the SVL coincided with this age-linked elevation in apoptosis. In agreement with CR's ability, TNF-alpha stimulation of both inflammatory and apoptotic pathways were abrogated. Our results suggest that TNF-alpha signals transmitted to specific fiber types determine the decision of selecting life or death signaling pathways and are linked to the extent of fiber loss experienced in the aging muscle. Such a specific potential may constitute a major proponent in the pathogenesis of sarcopenia.

Authors+Show Affiliations

University of Florida, Department of Aging and Geriatric Research, College of Medicine, Biochemistry of Aging Laboratory, Gainesville, Florida 32611, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15665035

Citation

Phillips, Tracey, and Christiaan Leeuwenburgh. "Muscle Fiber Specific Apoptosis and TNF-alpha Signaling in Sarcopenia Are Attenuated By Life-long Calorie Restriction." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 19, no. 6, 2005, pp. 668-70.
Phillips T, Leeuwenburgh C. Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction. FASEB J. 2005;19(6):668-70.
Phillips, T., & Leeuwenburgh, C. (2005). Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 19(6), 668-70.
Phillips T, Leeuwenburgh C. Muscle Fiber Specific Apoptosis and TNF-alpha Signaling in Sarcopenia Are Attenuated By Life-long Calorie Restriction. FASEB J. 2005;19(6):668-70. PubMed PMID: 15665035.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Muscle fiber specific apoptosis and TNF-alpha signaling in sarcopenia are attenuated by life-long calorie restriction. AU - Phillips,Tracey, AU - Leeuwenburgh,Christiaan, Y1 - 2005/01/21/ PY - 2005/1/25/pubmed PY - 2005/12/15/medline PY - 2005/1/25/entrez SP - 668 EP - 70 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J VL - 19 IS - 6 N2 - Increased tumor necrosis factor-alpha (TNF-alpha) levels have been found with age and are connected to muscle atrophy and cell loss, yet the signaling events that occur in vivo are unknown. Calorie restriction (CR), a robust intervention shown to repeatedly evade the physiological declines associated with aging, has been reported to reduce TNF-alpha and may assist in understanding the mechanisms of muscle sarcopenia. The effects of age and CR on muscle mass, myocyte area, fiber number, myocyte TNF-alpha expression, plasma TNF-alpha levels, and specific elements linked with the TNF-alpha signaling cascade (TNF-R1, IKKgamma, IkappaBalpha, p65, NF-kappaB binding activity, FADD, caspase-8, and DNA fragmentation) were investigated in soleus (predominately Type I fiber), and superficial vastus lateralis (SVL, predominately Type II fiber), of 6-month-old ad libitum fed (6AL), 26-month-old ad libitum fed (26AL), and 26-month-old calorie-restricted (26CR) male Fischer 344 rats (CR = 40% restriction compared with ad libitum). Plasma TNF-alpha was increased with age, and the age-associated rise was attenuated with life-long CR. In soleus muscle, we reported a greater capacity to cultivate inflammatory signaling through the transcription factor NF-kappaB compared with that detected in SVL with age. In contrast, in the SVL TNF-alpha stimulated apoptotic signaling with age to a much higher extent than was observed in the soleus. Moreover, a reduction in muscle mass, cross-sectional area, and fiber number in the SVL coincided with this age-linked elevation in apoptosis. In agreement with CR's ability, TNF-alpha stimulation of both inflammatory and apoptotic pathways were abrogated. Our results suggest that TNF-alpha signals transmitted to specific fiber types determine the decision of selecting life or death signaling pathways and are linked to the extent of fiber loss experienced in the aging muscle. Such a specific potential may constitute a major proponent in the pathogenesis of sarcopenia. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/15665035/Muscle_fiber_specific_apoptosis_and_TNF_alpha_signaling_in_sarcopenia_are_attenuated_by_life_long_calorie_restriction_ L2 - https://doi.org/10.1096/fj.04-2870fje DB - PRIME DP - Unbound Medicine ER -