SUMMARY: Bigger animals live longer. The scaling exponent for the relationship between lifespan and body mass is between 0.15 and 0.3. Bigger animals also expend more energy, and the scaling exponent for the relationship of resting metabolic rate (RMR) to body mass lies somewhere between 0.66 and 0.8. Mass-specific RMR therefore scales with a corresponding exponent between -0.2 and -0.33. Because the exponents for mass-specific RMR are close to the exponents for lifespan, but have opposite signs, their product (the mass-specific expenditure of energy per lifespan) is independent of body mass(exponent between -0.08 and 0.08). This means that across species a gram of tissue on average expends about the same amount of energy before it dies regardless of whether that tissue is located in a shrew, a cow, an elephant or a whale. This fact led to the notion that ageing and lifespan are processes regulated by energy metabolism rates and that elevating metabolism will be associated with premature mortality - the rate of living theory.The free-radical theory of ageing provides a potential mechanism that links metabolism to ageing phenomena, since oxygen free radicals are formed as a by-product of oxidative phosphorylation. Despite this potential synergy in these theoretical approaches, the free-radical theory has grown in stature while the rate of living theory has fallen into disrepute. This is primarily because comparisons made across classes (for example, between birds and mammals) do not conform to the expectations, and even within classes there is substantial interspecific variability in the mass-specific expenditure of energy per lifespan. Using interspecific data to test the rate of living hypothesis is, however, confused by several major problems. For example,appeals that the resultant lifetime expenditure of energy per gram of tissue is `too variable' depend on the biological significance rather than the statistical significance of the variation observed. Moreover, maximum lifespan is not a good marker of ageing and RMR is not a good measure of total energy metabolism. Analysis of residual lifespan against residual RMR reveals no significant relationship. However, this is still based on RMR.A novel comparison using daily energy expenditure (DEE), rather than BMR,suggests that lifetime expenditure of energy per gram of tissue is NOT independent of body mass, and that tissue in smaller animals expends more energy before expiring than tissue in larger animals. Some of the residual variation in this relationship in mammals is explained by ambient temperature. In addition there is a significant negative relationship between residual lifespan and residual daily energy expenditure in mammals. A potentially much better model to explore the links of body size, metabolism and ageing is to examine the intraspecific links. These studies have generated some data that support the original rate of living theory and other data that conflict. In particular several studies have shown that manipulating animals to expend more or less energy generate the expected effects on lifespan (particularly when the subjects are ectotherms). However, smaller individuals with higher rates of metabolism live longer than their slower, larger conspecifics.An addition to these confused observations has been the recent suggestion that under some circumstances we might expect mitochondria to produce fewer free radicals when metabolism is higher - particularly when they are uncoupled. These new ideas concerning the manner in which mitochondria generate free radicals as a function of metabolism shed some light on the complexity of observations linking body size, metabolism and lifespan.

Life-history trade-offs between components of fitness arise because reproduction entails both gains and costs. Costs of reproduction can be divided into ecological and physiological costs. The latter have been rarely studied yet are probably a dominant component of the effect. A deeper understanding of life-history evolution will only come about once these physiological costs are better understood. Physiological costs may be direct or indirect. Direct costs include the energy and nutrient demands of the reproductive event, and the morphological changes that are necessary to facilitate achieving these demands. Indirect costs may be optional ‘compensatory costs’ whereby the animal chooses to reduce investment in some other aspect of its physiology to maximize the input of resource to reproduction. Such costs may be distinguished from consequential costs that are an inescapable consequence of the reproductive event. In small mammals, the direct costs of reproduction involve increased energy, protein and calcium demands during pregnancy, but most particularly during lactation. Organ remodelling is necessary to achieve the high demands of lactation and involves growth of the alimentary tract and associated organs such as the liver and pancreas. Compensatory indirect costs include reductions in thermogenesis, immune function and physical activity. Obligatory consequential costs include hyperthermia, bone loss, disruption of sleep patterns and oxidative stress. This is unlikely to be a complete list. Our knowledge of these physiological costs is currently at best described as rudimentary. For some, we do not even know whether they are compensatory or obligatory. For almost all of them, we have no idea of exact mechanisms or how these costs translate into fitness trade-offs.

Summary: Two theories of how energy metabolism should be associated with longevity, both mediated via free‐radical production, make completely contrary predictions. The ‘rate of living‐free‐radical theory’ (Pearl, 1928;Harman, 1956;Sohal, 2002) suggests a negative association, the ‘uncoupling to survive’ hypothesis (Brand, 2000) suggests the correlation should be positive. Existing empirical data on this issue is contradictory and extremely confused (Rubner, 1908;Yan & Sohal, 2000;Ragland & Sohal, 1975;Daanet al., 1996;Wolf & Schmid‐Hempel, 1989]. We sought associations between longevity and individual variations in energy metabolism in a cohort of outbred mice. We found a positive association between metabolic intensity (kJ daily food assimilation expressed as g/body mass) and lifespan, but no relationships of lifespan to body mass, fat mass or lean body mass. Mice in the upper quartile of metabolic intensities had greater resting oxygen consumption by 17% and lived 36% longer than mice in the lowest intensity quartile. Mitochondria isolated from the skeletal muscle of mice in the upper quartile had higher proton conductance than mitochondria from mice from the lowest quartile. The higher conductance was caused by higher levels of endogenous activators of proton leak through the adenine nucleotide translocase and uncoupling protein‐3. Individuals with high metabolism were therefore more uncoupled, had greater resting and total daily energy expenditures and survived longest – supporting the ‘uncoupling to survive’ hypothesis.

A fundamental principle of nutrition and metabolism is that body weight change is associated with an imbalance between the energy content of food eaten and ener

A lifetime of change: Measurements of total and basal energy in a large cohort of subjects at ages spanning from before birth to old age document distinct changes that occur during a human lifetime. Pontzer et al . report that energy expenditure (adjusted for weight) in neonates was like that of adults but increased substantially in the first year of life (see the Perspective by Rhoads and Anderson). It then gradually declined until young individuals reached adult characteristics, which were maintained from age 20 to 60 years. Older individuals showed reduced energy expenditure. Tissue metabolism thus appears not to be constant but rather to undergo transitions at critical junctures. —LBR