Forever Young: Mechanisms of Natural Anoxia Tolerance and Potential Links to Longevity

Abstract

While mammals cannot survive oxygen deprivation for more than a few minutes without sustaining severe organ damage, some animals have mastered anaerobic life. Freshwater turtles belonging to the Trachemys and Chrysemys genera are the champion facultative anaerobes of the vertebrate world, often surviving without oxygen for many weeks at a time. The physiological and biochemical mechanisms that underlie anoxia tolerance in turtles include profound metabolic rate depression, post-translational modification of proteins, strong antioxidant defenses, activation of specific stress-responsive transcription factors, and enhanced expression of cyto-protective proteins. Turtles are also known for their incredible longevity and display characteristics of “negligible senescence.” We propose that the robust stress-tolerance mechanisms that permit long term anaerobiosis by turtles may also support the longevity of these animals. Many of the mechanisms involved in natural anoxia tolerance, such as hypometabolism or the induction of various protective proteins/pathways, have been shown to play important roles in mammalian oxygen-related diseases and improved understanding of how cells survive without oxygen could aid in the understanding and treatment of various pathological conditions that involve hypoxia or oxidative stress. In the present review we discuss the recent advances made in understanding the molecular nature of anoxia tolerance in turtles and the potential links between this tolerance and longevity.

Each to their own: skeletal muscles of different function use different biochemical strategies during aestivation at high temperature

“…Additionally, the significant increase in Hsp70 in aestivating gastrocnemius relative to controls may be associated with constraining protein carbonylation at control levels (Fredriksson et al, 2005). Alternatively, Hsp70's role may be in protecting the cellular proteome because of the fact that protein carbonylation continues at control levels in aestivation (Krivoruchko and Storey, 2010).…”

“…In addition to antioxidants, heat shock proteins (HSPs) also function during oxidative stress (Kalmar and Greensmith, 2009;Krivoruchko and Storey, 2010;Wallen et al, 1997), facilitating stress sensing, signalling and protein protection (Liu and Steinacker, 2001;Liu et al, 2006;Sørensen et al, 2003). HSPs are regulated in models of muscle disuse (Desplanches et al, 2004;Seo et al, 2006) as well as during dormancy (Lee et al, 2008), and their expression can be tissue and muscle specific (Flanagan et al, 1995;Locke et al, 1991).…”

Heat shock proteins and hypometabolism: adaptive strategy for proteome preservation

“…22 More recently, it is becoming clear that HSPs (and other elements of the stress response) also play roles in longevity and life extension. 27,28 What has not been fully appreciated previously is the concept that HSPs also contribute to preparatory programs that set up organisms for long-term survival in hypometabolic states. This latter concept is the focus of the present review.…”

Regulation of hypometabolism: insights into epigenetic controls

“…Epigenetic mechanisms also appear to be involved in suppressing gene transcription during anoxic submergence of turtles (Trachemys scripta elegans), a well-studied model of vertebrate anoxia tolerance (Storey, 2007;Krivoruchko and Storey, 2010a). This species (and some other freshwater turtles) undergoes frequent hypoxia/anoxia excursions as a consequence of diving, but most impressively can endure prolonged submergence in cold water without breathing for many weeks during the winter (Jackson and Ultsch, 2010).…”