TY - JOUR
T1 - Mitochondrial death effectors
T2 - Relevance to sarcopenia and disuse muscle atrophy
AU - Marzetti, Emanuele
AU - Hwang, Judy C.Y.
AU - Lees, Hazel A.
AU - Wohlgemuth, Stephanie E.
AU - Dupont-Versteegden, Esther E.
AU - Carter, Christy S.
AU - Bernabei, Roberto
AU - Leeuwenburgh, Christiaan
PY - 2010/3
Y1 - 2010/3
N2 - Accelerated apoptosis in skeletal muscle is increasingly recognized as a potential mechanism contributing to the development of sarcopenia of aging and disuse muscle atrophy. Given their central role in the regulation of apoptosis, mitochondria are regarded as key players in the pathogenesis of myocyte loss during aging and other atrophying conditions. Oxidative damage to mitochondrial constituents, impaired respiration and altered mitochondrial turnover have been proposed as potential triggering events for mitochondrial apoptotic signaling. In addition, iron accumulation within mitochondria may enhance the susceptibility to apoptosis during the development of sarcopenia and possibly acute muscle atrophy, likely through exacerbation of oxidative stress. Mitochondria can induce myocyte apoptosis via both caspase-dependent and independent pathways, although the apoptogenic mediators involved may be different depending on age, muscle type and specific atrophying conditions. Despite the considerable advances made, additional research is necessary to establish a definite causal link between apoptotic signaling and the development of sarcopenia and acute atrophy. Furthermore, a translational effort is required to determine the role played by apoptosis in the pathogenesis of sarcopenia and disuse-induced muscle loss in human subjects.
AB - Accelerated apoptosis in skeletal muscle is increasingly recognized as a potential mechanism contributing to the development of sarcopenia of aging and disuse muscle atrophy. Given their central role in the regulation of apoptosis, mitochondria are regarded as key players in the pathogenesis of myocyte loss during aging and other atrophying conditions. Oxidative damage to mitochondrial constituents, impaired respiration and altered mitochondrial turnover have been proposed as potential triggering events for mitochondrial apoptotic signaling. In addition, iron accumulation within mitochondria may enhance the susceptibility to apoptosis during the development of sarcopenia and possibly acute muscle atrophy, likely through exacerbation of oxidative stress. Mitochondria can induce myocyte apoptosis via both caspase-dependent and independent pathways, although the apoptogenic mediators involved may be different depending on age, muscle type and specific atrophying conditions. Despite the considerable advances made, additional research is necessary to establish a definite causal link between apoptotic signaling and the development of sarcopenia and acute atrophy. Furthermore, a translational effort is required to determine the role played by apoptosis in the pathogenesis of sarcopenia and disuse-induced muscle loss in human subjects.
KW - Apoptosis
KW - Apoptosis-inducing factor
KW - Caspases
KW - Endonuclease G
KW - Iron
KW - Mitochondria
KW - Muscle atrophy
KW - Sarcopenia
UR - http://www.scopus.com/inward/record.url?scp=76749136290&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76749136290&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2009.05.007
DO - 10.1016/j.bbagen.2009.05.007
M3 - Review article
C2 - 19450666
AN - SCOPUS:76749136290
SN - 0304-4165
VL - 1800
SP - 235
EP - 244
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 3
ER -