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 apo...

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Bibliographic Details
Published in:Mechanisms of ageing and development 2007-02, Vol.128 (2), p.213-221
Main Authors: Zhang, Yingpei, Padalecki, Susan S., Chaudhuri, Asish R., De Waal, Eric, Goins, Beth A., Grubbs, Barry, Ikeno, Yuji, Richardson, Arlan, Mundy, Gregory R., Herman, Brian
Format: Article
Language:English
Subjects:
Adipose Tissue - physiology
Aging - genetics
Aging - physiology
Animals
Apoptosis - genetics
Apoptosis - physiology
Biological and medical sciences
Bone
Bone Density - genetics
Bone Resorption
Caspase 2 - genetics
Caspase 2 - metabolism
Caspase-2
Cysteine - metabolism
Development. Metamorphosis. Moult. Ageing
Fat
Fundamental and applied biological sciences. Psychology
Hair - growth & development
Hair - physiology
Hair growth
Liver - metabolism
Longevity - physiology
Maximum lifespan
Mice
Mice, Knockout
Neoplasms - epidemiology
Neoplasms - genetics
Oxidative Stress
Proteins - metabolism
Survival Rate
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary: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.
ISSN:0047-6374
1872-6216
DOI:10.1016/j.mad.2006.11.030