The Gray Mouse Lemur: A Model for Studies of Primate Metabolic Rate Depression

The use of daily torpor and/or of multi-day torpor bouts during a hibernation season are energy-saving survival strategies that have been well-studied for many years, particularly for small mammals living in seasonally-cold environments. Both phenomena are characterized by a regulated suppression of metabolic rate, a slowing of many physiological processes (e.g., heart and breathing rates, organ perfusion, kidney filtration, and neurological activity), and heterothermy that allows core body temperature (Tb) to fall to near-ambient, often to values close to 0 C for small hibernators [1–4]. All of these concepts are largely alien to our experience as humans. For example, hypothermia in humans is clinically diagnosed if core Tb drops to 34–35 C and the risk of cardiac arrest and death is very high if core Tb is less than about 28 C [5]. The natural capacity for metabolic suppression in humans is quite limited with only small reductions in metabolic rate and Tb, when recorded in deep meditative states [6], during starvation [7], or in newborns exposed to hypoxia [8]. However, biomedical researchers envision a range of applications that can be derived from a thorough understanding of the natural mechanisms that regulate daily torpor and multi-day hibernation. Chief among these is the development of methods to expand the use of organ transplantation as a medical therapy by using preservation strategies derived from the natural mechanisms of torpor and/or hypothermia tolerance displayed by various mammalian species. Mechanisms to induce whole body torpor are also envisioned as a beneficial treatment when injured persons need to be transported long distances to medical care, when patient recovery could be aided by a prolonged torpid state, or even as an aid to long-term space flight. The best model animal for such studies has long been sought. Long-standing models of torpor and hibernation are mainly rodents (e.g., ground squirrels, marmots, hamsters, and mice), although considerable work has also been done on bats, some small marsupials and a few others [4]. Although much information about the molecular, biochemical and physiological mechanisms of natural hibernation has been derived from these studies [1–4], there are some questions about the applicability of this work to development of inducible torpor in humans. For example: (1) would the genes, proteins, and molecular mechanisms involved in torpor/ hibernation in rodents also apply to humans? and (2) is endurance of very low Tb values, such as typically occurring during rodent hibernation, actually necessary for the preservation applications envisioned for humans or their isolated organs? The latter question is actually relevant in that some recent studies are showing that warm perfusion of excised human organs during transfer from donor to recipient is an effective and potentially less injurious option than the cold ischemia (packing in ice) that has been the standard for many years [9,10]. We believe that the ultimate model of relevance to human biomedical concerns would be a primate species that exhibits natural torpor/hibernation. Such species exist; studies in recent years have documented both daily torpor and seasonal hibernation among several Afrotropical mammals [11] including seven small lemur species from Madagascar, all belonging to