Is metabolic rate a universal ‘pacemaker’ for biological processes?

Abstract

A common, long-held belief is that metabolic rate drives the rates of various biological, ecological and evolutionary processes. Although this metabolic pacemaker view (as assumed by the recent, influential 'metabolic theory of ecology') may be true in at least some situations (e.g. those involving moderate temperature effects or physiological processes closely linked to metabolism, such as heartbeat and breathing rate), it suffers from several major limitations, including: (i) it is supported chiefly by indirect, correlational evidence (e.g. similarities between the body-size and temperature scaling of metabolic rate and that of other biological processes, which are not always observed) - direct, mechanistic or experimental support is scarce and much needed; (ii) it is contradicted by abundant evidence showing that various intrinsic and extrinsic factors (e.g. hormonal action and temperature changes) can dissociate the rates of metabolism, growth, development and other biological processes; (iii) there are many examples where metabolic rate appears to respond to, rather than drive the rates of various other biological processes (e.g. ontogenetic growth, food intake and locomotor activity); (iv) there are additional examples where metabolic rate appears to be unrelated to the rate of a biological process (e.g. ageing, circadian rhythms, and molecular evolution); and (v) the theoretical foundation for the metabolic pacemaker view focuses only on the energetic control of biological processes, while ignoring the importance of informational control, as mediated by various genetic, cellular, and neuroendocrine regulatory systems. I argue that a comprehensive understanding of the pace of life must include how biological activities depend on both energy and information and their environmentally sensitive interaction. This conclusion is supported by extensive evidence showing that hormones and other regulatory factors and signalling systems coordinate the processes of growth, metabolism and food intake in adaptive ways that are responsive to an organism's internal and external conditions. Metabolic rate does not merely dictate growth rate, but is coadjusted with it. Energy and information use are intimately intertwined in living systems: biological signalling pathways both control and respond to the energetic state of an organism. This review also reveals that we have much to learn about the temporal structure of the pace of life. Are its component processes highly integrated and synchronized, or are they loosely connected and often discordant? And what causes the level of coordination that we see? These questions are of great theoretical and practical importance.

Effects of Contingency versus Constraints on the Body-Mass Scaling of Metabolic Rate

“…It invokes effects of T a on growth rate, which cannot explain negative associations between T a and the metabolic scaling exponent commonly observed in ectothermic organisms. Decreasing T a inhibits growth rate, and decreased growth rates are associated with lower, not higher metabolic scaling exponents (see [10,32,44,96]). …”

“…Although the importance of regulation in metabolic scaling was discussed over 50 years ago (e.g., [20,106,122]), it has been a neglected focus of research in recent years (but see [10,27,96,123,124]). The effects of regulation can be dramatic, as seen when mammals engage in regulated depression of their T b and metabolic rate during torpor and hibernation [125]: as a result, their metabolic scaling slope shifts markedly from~0.67-0.75 to~1, as predicted by the MLBH [10,23,26,93].…”

“…Therefore, I recommend that increased attention should be given to how various regulatory systems at various levels of biological organization (from biochemical signaling pathways to neuroendocrine systems) affect metabolic scaling. Metabolic scaling is not merely the result of physical constraints, but is also mediated by various regulated processes involving resource supply and demand, metabolic waste removal, and heat dissipation [10,27,96].…”

Rediscovering and Reviving Old Observations and Explanations of Metabolic Scaling in Living Systems

“…These include models or hypotheses invoking the effects of four-dimensional geometry, sometimes including biological time as the fourth dimension [17,[77][78][79][80][81][82][83][84], the relative effects of resource supply versus demand (e.g., [19,20,46,70,[85][86][87][88][89][90]), the biological regulation of metabolic rate (e.g., [20,87,[90][91][92][93][94][95][96][97][98]), and various adaptive effects resulting from interactions with ecological factors (e.g., [19,20,46,[99][100][101][102][103][104][105][106][107]). Here I focus on four major, much-discussed theoretical approaches encompassed by the 'contextual multimodal theory' (CMT) of metabolic scaling ( Figure 1) recently proposed in this journal [20].…”

“…For example, Harrison [106] recently assembled extensive evidence (some of it new) contradicting oxygen limitation as a general mechanism, including that oxygen availability to cells is not lower in large versus small animals, contrary to that predicted. Other workers have also discussed additional lines of evidence contradicting the predictions of RTN models (e.g., [19,20,46,97,98,[132][133][134]). For instance, cells extracted from homogeneous tissues and cultured in vitro in oxygen-and nutrient-rich media often exhibit lower, rather than higher metabolic rates than those in vivo [reviewed in [97]), contrary to that predicted by RTN models [171,172].…”