TY - JOUR
T1 - Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle
AU - Marzetti, Emanuele
AU - Wohlgemuth, Stephanie Eva
AU - Lees, Hazel Anne
AU - Chung, Hae-Young
AU - Giovannini, Silvia
AU - Leeuwenburgh, Christiaan
PY - 2008
Y1 - 2008
N2 - Mitochondria-mediated apoptosis represents a central process driving age-related muscle loss. However, the temporal relation between mitochondrial apoptotic signaling and sarcopenia as well as the regulation of release of pro-apoptotic factors from the mitochondria has not been elucidated. In this study, we investigated mitochondrial apoptotic signaling in skeletal muscle of rats across a wide age range. We also investigated whether mitochondrial-driven apoptosis was accompanied by changes in the expression of Bcl-2 proteins and components of the mitochondrial permeability transition pore (mPTP). Analyses were performed on gastrocnemius muscle of 8-, 18-, 29- and 37-month-old male Fischer344 × Brown Norway rats (9 per group). Muscle weight declined progressively with advancing age, concomitant with increased apoptotic DNA fragmentation. Cytosolic and nuclear levels of apoptosis inducing factor (AIF) and endonuclease G (EndoG) increased in old and senescent animals. In contrast, cytosolic levels of cytochrome c were unchanged with age. Mitochondrial Bcl-2, Bax and Bid increased dramatically in 37-month-old rats, with no changes in the Bax/Bcl-2 ratio in any of the age groups. Finally, expression of cyclophilin D (CyPD) was enhanced at very old age. Our findings indicate that the mitochondrial caspase-independent apoptotic pathway may play a more prominent role in skeletal muscle loss than caspase-mediated apoptosis. © 2008 Elsevier Ireland Ltd. All rights reserved.
AB - Mitochondria-mediated apoptosis represents a central process driving age-related muscle loss. However, the temporal relation between mitochondrial apoptotic signaling and sarcopenia as well as the regulation of release of pro-apoptotic factors from the mitochondria has not been elucidated. In this study, we investigated mitochondrial apoptotic signaling in skeletal muscle of rats across a wide age range. We also investigated whether mitochondrial-driven apoptosis was accompanied by changes in the expression of Bcl-2 proteins and components of the mitochondrial permeability transition pore (mPTP). Analyses were performed on gastrocnemius muscle of 8-, 18-, 29- and 37-month-old male Fischer344 × Brown Norway rats (9 per group). Muscle weight declined progressively with advancing age, concomitant with increased apoptotic DNA fragmentation. Cytosolic and nuclear levels of apoptosis inducing factor (AIF) and endonuclease G (EndoG) increased in old and senescent animals. In contrast, cytosolic levels of cytochrome c were unchanged with age. Mitochondrial Bcl-2, Bax and Bid increased dramatically in 37-month-old rats, with no changes in the Bax/Bcl-2 ratio in any of the age groups. Finally, expression of cyclophilin D (CyPD) was enhanced at very old age. Our findings indicate that the mitochondrial caspase-independent apoptotic pathway may play a more prominent role in skeletal muscle loss than caspase-mediated apoptosis. © 2008 Elsevier Ireland Ltd. All rights reserved.
KW - AIF
KW - Apoptosis
KW - Endonuclease G
KW - Permeability transition pore
KW - Sarcopenia
KW - AIF
KW - Apoptosis
KW - Endonuclease G
KW - Permeability transition pore
KW - Sarcopenia
UR - http://hdl.handle.net/10807/164845
U2 - 10.1016/j.mad.2008.05.005
DO - 10.1016/j.mad.2008.05.005
M3 - Article
SN - 0047-6374
VL - 129
SP - 542
EP - 549
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
ER -