Caspase-2 deficiency enhances aging-related traits in mice

Yingpei Zhang, Susan S. Padalecki, Asish R. Chaudhuri, Eric De Waal, Beth A. Goins, Barry Grubbs, Yuji Ikeno, Arlan Richardson, Gregory R. Mundy, Brian Herman

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60 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)213-221
Number of pages9
JournalMechanisms of Ageing and Development
Volume128
Issue number2
DOIs
StatePublished - Feb 1 2007

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Keywords

  • Bone
  • Caspase-2
  • Fat
  • Hair growth
  • Maximum lifespan

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

Cite this

Zhang, Y., Padalecki, S. S., Chaudhuri, A. R., De Waal, E., Goins, B. A., Grubbs, B., Ikeno, Y., Richardson, A., Mundy, G. R., & Herman, B. (2007). Caspase-2 deficiency enhances aging-related traits in mice. Mechanisms of Ageing and Development, 128(2), 213-221. https://doi.org/10.1016/j.mad.2006.11.030