Caspase-2 deficiency enhances aging-related traits in mice.
Alteration of apoptotic activity has been observed in a number of tissues in aging mammals, but it remains unclear whether and/or how apoptosis may affect aging. Caspase-2 is a member of the cysteine protease family that plays a critical role in apoptosis. To understand the impact of compromised apoptosis function on mammalian aging, we conducted a comparative study on caspase-2 deficient mice and their wild-type littermates with a specific focus on the aging-related traits at advanced ages. We found that caspase-2 deficiency enhanced a number of traits commonly seen in premature aging animals. Loss of caspase-2 was associated with shortened maximum lifespan, impaired hair growth, increased bone loss, and reduced body fat content. In addition, we found that the livers of caspase-2 deficient mice had higher levels of oxidized proteins than those of age-matched wild-type mice, suggesting that caspase-2 deficiency compromised the animal's ability to clear oxidatively damaged cells. Collectively, these results suggest that caspase-2 deficiency affects aging in the mice. This study thus demonstrates for the first time that disruption of a key apoptotic gene has a significant impact on aging.
Zhang
Yingpei
Y
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States.
Padalecki
Susan S
SS
Chaudhuri
Asish R
AR
De Waal
Eric
E
Goins
Beth A
BA
Grubbs
Barry
B
Ikeno
Yuji
Y
Richardson
Arlan
A
Mundy
Gregory R
GR
Herman
Brian
B
D000273:Adipose Tissue / Q000502:physiology; D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D015519:Bone Density / Q000235:genetics; D001862:Bone Resorption; D053143:Caspase 2 / Q000235:genetics* / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D006197:Hair / Q000254:growth & development / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008136:Longevity / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism; D015996:Survival Rate
D011506:Proteins; D053143:Caspase 2; D003545:Cysteine