Caloric restriction and longevity: Effects of reduced body temperature

Abstract

Caloric restriction (CR) causes a reduction in body temperature (T_b) which is suggested to contribute to changes that increase lifespan. Moreover, low T_b has been shown to improve health and longevity independent of CR. In this review we examine the connections between CR, T_b and mechanisms that influence longevity and ageing. Recent findings regarding the overlapping mechanisms of CR and T_b that benefit longevity are discussed, including changes in body composition, hormone regulation, and gene expression, as well as reductions in low-level inflammation and reactive oxygen species-induced molecular damage. This information is summarized in a model describing how CR and low T_b, both synergistically and independently, increase lifespan. Moreover, the nascent notion that the rate of ageing may be pre-programmed in response to environmental influences at critical periods of early development is also considered. Based on current evidence, it is concluded that low T_b plays an integral role in mediating the effects of CR on health and longevity, and that low T_b may exert independent biological changes that increase lifespan. Our understanding of the overlap between CR- and T_b-mediated longevity remains incomplete and should be explored in future research.

Introduction

Organismal senescence, or deterioration, is characterized by progressive entropy, a gradual increase in molecular disorder that ultimately increases an organism's risk for mortality (Waters, 2007). Somatic deterioration, however, does not follow an orchestrated age-associated progression. It has been suggested that only 25–30% of lifespan variation can be attributed to genetic factors (Ljungquist et al., 1998, McGue et al., 1993). Thus, the accumulation of molecular disorder that contributes to somatic deterioration is subject to considerable plasticity. This phenomenon has been targeted by scientists with the expectation that advancements could compress morbidity, as well as lower disease and mortality risk. Attempts to understand the rate of human deteriorative processes, along with the exploration of longevity determinants substantially contributes to current biogerontology research (Braeckman et al., 2002, Conti et al., 2006, Houthoofd et al., 2002).

Reports highlighting the biological advantages of caloric restriction (CR) have been circulating since 1935 (McCay et al., 1935). However, the mechanisms responsible for the benefits observed during CR have been difficult to isolate because CR exerts pleiotropic effects that influence several biological systems [reviewed in Walford et al., 1987]. For example, biogerontologists continue to consider the importance of thermal biology and its influence on longevity that stems from the observation that CR reduces body temperature (T_b) (Duffy et al., 1990b, Lane et al., 1996). Indeed, it has been suggested that part of the longevity conferred by CR depends on a reduction in T_b (Tabarean et al., 2010). Ageing thermobiology research has crept away from CR since the suggestion that a low T_b may independently benefit lifespan (Conti et al., 2006, Kent, 1978). Yet, our understanding regarding the mechanisms responsible for this phenomenon remains limited. Relevant findings suggest that the influence of low T_b on longevity in homeotherms may act through mechanisms similar to those that mediate CR (Conti et al., 2006). Conversely, high ambient temperatures, such as that experienced during the August 2003 heat wave in Western Europe, have significant adverse health implications (Klenk et al., 2010). Given the global concerns of increasing ambient temperatures and its important relationship with population ageing (Costello et al., 2009), knowledge of potential mechanisms that expose the inner workings of the connections between T_b with health and longevity is becoming increasingly important. With a focus on mammalian models, we review the relationship between T_b and CR and their influence on ageing and longevity.