Caspase-2 deficiency enhances aging-related traits in mice.

Authors: Zhang Y; Padalecki SS; Chaudhuri AR; De Waal E; Goins BA; Grubbs B; Ikeno Y; Richardson A; Mundy GR; Herman B

Abstract: 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.

Keywords: Adipose Tissue/physiology; Aging/*genetics/physiology; Animals; Apoptosis/*genetics/physiology; Bone Density/genetics; Bone Resorption; Caspase 2/*genetics/metabolism; Cysteine/metabolism; Hair/growth & development/physiology; Liver/metabolism; Longevity/physiology; Mice; Mice, Knockout; Neoplasms/epidemiology/genetics; Oxidative Stress; Proteins/metabolism; Survival Rate
Journal: Mechanisms of ageing and development
Volume: 128
Issue: 2
Pages: 213-21
Date: Dec. 26, 2006
PMID: 17188333
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Citation:

Zhang Y, Padalecki SS, Chaudhuri AR, De Waal E, Goins BA, Grubbs B, Ikeno Y, Richardson A, Mundy GR, Herman B (2007) Caspase-2 deficiency enhances aging-related traits in mice. Mechanisms of ageing and development 128: 213-21.


Study Lifespan Factors:
  • Casp2 caspase 2


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