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

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


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
Issue number2
StatePublished - Feb 2007


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

ASJC Scopus subject areas

  • Aging
  • Developmental Biology


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