Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes

Pedersen, Maria; Bruunsgaard, Helle; Weis, Nina; Hendel, Helle Westergren; Andreassen, Bente Utoft; Eldrup, Ebbe; Dela, Flemming; Pedersen, Bente Klarlund

doi:10.1016/s0047-6374(03)00027-7

Cited by 286 publications

(185 citation statements)

References 25 publications

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“…Several studies have also drawn associations between the increases in circulating cytokines and the sarcopenic process [11,13]. Specifically, elevated circulating levels of TNF-α are associated with lower appendicular skeletal muscle mass [11] and reduced knee extensor and grip strength [13]. Because we have found activation of the extrinsic apoptotic signaling pathway in muscles of old rats, we speculate that circulating TNF-α may be the initiator of this pathway in skeletal muscle.…”

Section: Effects Of Tnf-α In Skeletal Musclementioning

confidence: 55%

“…Based on the well-documented increase in circulating TNF-α levels with aging [6][7][8][9][10][11][12][13] and increases in apoptosis of myonuclei in aged skeletal muscles, [18,19,22], we examined whether apoptotic signaling via the extrinsic pathway contributed to sarcopenia. Our data show that pro-and anti-apoptotic proteins in the extrinsic apoptotic pathway are affected by aging in fast (plantaris) and slow (soleus) skeletal muscles of rats.…”

Section: Discussionmentioning

confidence: 99%

“…The circulating concentrations of specific cytokines have been shown to be elevated in the serum as a result of aging. In humans, serum levels of catabolic cytokines, such as TNF-α [7,9,12] and IL-6 [6,11,32], are increased in healthy elderly compared to young adults. Serum concentrations of TNF-α have been proposed as a prognostic marker of all cause-mortality in centenarians [7] and with age-associated pathology and mortality in 80-year old adults [9].…”

Section: Effects Of Tnf-α In Skeletal Musclementioning

confidence: 99%

“…Serum concentrations of TNF-α have been proposed as a prognostic marker of all cause-mortality in centenarians [7] and with age-associated pathology and mortality in 80-year old adults [9]. Several studies have also drawn associations between the increases in circulating cytokines and the sarcopenic process [11,13]. Specifically, elevated circulating levels of TNF-α are associated with lower appendicular skeletal muscle mass [11] and reduced knee extensor and grip strength [13].…”

Section: Effects Of Tnf-α In Skeletal Musclementioning

confidence: 99%

“…Although this phenomenon is well documented in animal and human studies, the underlying mechanisms leading to sarcopenia remain to be fully elucidated. The contributing mechanism(s) leading to sarcopenia are multi-factorial and may include: denervation and reinnervation of motor units, especially within skeletal muscles composed of a high degree of type II muscle fibers [1][2][3]; an alteration in the hormonal milieu in which anabolic hormone concentrations progressively decline [4,5]; elevated concentrations of inflammatory mediators that are not only associated with disease states, but also occur in healthy older adults [6][7][8][9][10][11][12][13]; and myonuclear loss through apoptotic mechanisms [14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Death receptor-associated pro-apoptotic signaling in aged skeletal muscle

2006

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Tumor necrosis factor-alpha (TNF-α) is elevated in the serum as a result of aging and it promotes pro-apoptotic signaling upon binding to the type I TNF receptor. It is not known if activation of this apoptotic pathway contributes to the well-documented age-associated decline in muscle mass (i.e. sarcopenia). We tested the hypothesis that skeletal muscles from aged rodents would exhibit elevations in markers involved in the extrinsic apoptotic pathway when compared to muscles from young adult rodents, thereby contributing to an increased incidence of nuclear apoptosis in these muscles. The plantaris (fast) and soleus (slow) muscles were studied in young adult (5-7 mo, n = 8) and aged (33 mo, n = 8) Fischer 344 × Brown Norway rats. Muscles from aged rats were significantly smaller while exhibiting a greater incidence of apoptosis. Furthermore, muscles from aged rats had higher type I TNF receptor and Fas associated death domain protein (FADD) mRNA, protein contents for FADD, BCL-2 Interacting Domain (Bid), FLICE-inhibitory protein (FLIP), and enzymatic activities of caspase-8 and caspase-3 than muscles from young adult rats. Significant correlations were observed in the plantaris muscle between caspase activity and muscle weight and the apoptotic index, while similar relationships were not found in the soleus. These data demonstrate that pro-apoptotic signaling downstream of the TNF receptor is active in aged muscles. Furthermore, our data extend the previous demonstration that type II fibers are preferentially affected by aging and support the hypothesis that type II fiber containing skeletal muscles may be more susceptible to muscle mass loses via the extrinsic apoptotic pathway.

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