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Geoffrey B West

Publications and source records attributed to Geoffrey B West.

9 recordsLinked to original sources
PubMed2007

A quantitative, theoretical framework for understanding mammalian sleep.

Sleep is one of the most noticeable and widespread phenomena occurring in multicellular animals. Nevertheless, no consensus for a theory of its origins has emerged. In particular, no explicit, quantitative theory exists that elucidates or distinguishes between the myriad hypotheses proposed for sleep. Here, we develop a general, quantitative theory for mammalian sleep that relates many of its fundamental parameters to metabolic rate and body size. Several mechanisms suggested for the function of sleep can be placed in this framework, e.g., cellular repair of damage caused by metabolic processes as well as cortical reorganization to process sensory input. Our theory leads to predictions for sleep time, sleep cycle time, and rapid eye movement time as functions of body and brain mass, and it explains, for example, why mice sleep approximately 14 hours per day relative to the 3.5 hours per day that elephants sleep. Data for 96 species of mammals, spanning six orders of magnitude in body size, are consistent with these predictions and provide strong evidence that time scales for sleep are set by the brain's, not the whole-body, metabolic rate.

Animals↗
PubMed2006

Systems approaches to the networks of aging.

The aging of an organism is the result of complex changes in structure and function of molecules, cells, tissues, and whole body systems. To increase our understanding of how aging works, we have to analyze and integrate quantitative evidence from multiple levels of biological organization. Here, we define a broader conceptual framework for a quantitative, computational systems biology approach to aging. Initially, we consider fractal supply networks that give rise to scaling laws relating body mass, metabolism and lifespan. This approach provides a top-down view of constrained cellular processes. Concomitantly, multi-omics data generation build such a framework from the bottom-up, using modeling strategies to identify key pathways and their physiological capacity. Multiscale spatio-temporal representations finally connect molecular processes with structural organization. As aging manifests on a systems level, it emerges as a highly networked process regulated through feedback loops between levels of biological organization.

Aging↗
PubMed2005

The metabolic basis of whole-organism RNA and phosphorus content.

Understanding the storage, flux, and turnover of nutrients in organisms is important for quantifying contributions of biota to biogeochemical cycles. Here we present a model that predicts the storage of phosphorus-rich RNA and whole-body phosphorus content in eukaryotes based on the mass- and temperature-dependence of ATP production in mitochondria. Data from a broad assortment of eukaryotes support the model's two main predictions. First, whole-body RNA concentration is proportional to mitochondrial density and consequently scales with body mass to the -1/4 power. Second, whole-body phosphorus content declines with increasing body mass in eukaryotic unicells but approaches a relatively constant value in large multicellular animals because the fraction of phosphorus in RNA decreases relative to the fraction in other pools. Extension of the model shows that differences in the flux of RNA-associated phosphorus are due to the size dependencies of metabolic rate and RNA concentration. Thus, the model explicitly links two biological currencies at the individual level: energy in the form of ATP and materials in the form of phosphorus, both of which are critical to the functioning of ecosystems. The model provides a framework for linking attributes of individuals to the storage and flux of phosphorus in ecosystems.

Animals↗
PubMed2005

The origin of allometric scaling laws in biology from genomes to ecosystems: towards a quantitative unifying theory of biological structure and organization.

Life is the most complex physical phenomenon in the Universe, manifesting an extraordinary diversity of form and function over an enormous scale from the largest animals and plants to the smallest microbes and subcellular units. Despite this many of its most fundamental and complex phenomena scale with size in a surprisingly simple fashion. For example, metabolic rate scales as the 3/4-power of mass over 27 orders of magnitude, from molecular and intracellular levels up to the largest organisms. Similarly, time-scales (such as lifespans and growth rates) and sizes (such as bacterial genome lengths, tree heights and mitochondrial densities) scale with exponents that are typically simple powers of 1/4. The universality and simplicity of these relationships suggest that fundamental universal principles underly much of the coarse-grained generic structure and organisation of living systems. We have proposed a set of principles based on the observation that almost all life is sustained by hierarchical branching networks, which we assume have invariant terminal units, are space-filling and are optimised by the process of natural selection. We show how these general constraints explain quarter power scaling and lead to a quantitative, predictive theory that captures many of the essential features of diverse biological systems. Examples considered include animal circulatory systems, plant vascular systems, growth, mitochondrial densities, and the concept of a universal molecular clock. Temperature considerations, dimensionality and the role of invariants are discussed. Criticisms and controversies associated with this approach are also addressed.

Body Size↗
PubMed2004

The rate of DNA evolution: effects of body size and temperature on the molecular clock.

Observations that rates of molecular evolution vary widely within and among lineages have cast doubts on the existence of a single "molecular clock." Differences in the timing of evolutionary events estimated from genetic and fossil evidence have raised further questions about the accuracy of molecular clocks. Here, we present a model of nucleotide substitution that combines theory on metabolic rate with the now-classic neutral theory of molecular evolution. The model quantitatively predicts rate heterogeneity and may reconcile differences in molecular- and fossil-estimated dates of evolutionary events. Model predictions are supported by extensive data from mitochondrial and nuclear genomes. By accounting for the effects of body size and temperature on metabolic rate, this model explains heterogeneity in rates of nucleotide substitution in different genes, taxa, and thermal environments. This model also suggests that there is indeed a single molecular clock, as originally proposed by Zuckerkandl and Pauling [Zuckerkandl, E. & Pauling, L. (1965) in Evolving Genes and Proteins, eds. Bryson, V. & Vogel, H. J. (Academic, New York), pp. 97-166], but that it "ticks" at a constant substitution rate per unit of mass-specific metabolic energy rather than per unit of time. This model therefore links energy flux and genetic change. More generally, the model suggests that body size and temperature combine to control the overall rate of evolution through their effects on metabolism.

Animals↗
PubMed2002

The fractal nature of nature: power laws, ecological complexity and biodiversity.

Underlying the diversity of life and the complexity of ecology is order that reflects the operation of fundamental physical and biological processes. Power laws describe empirical scaling relationships that are emergent quantitative features of biodiversity. These features are patterns of structure or dynamics that are self-similar or fractal-like over many orders of magnitude. Power laws allow extrapolation and prediction over a wide range of scales. Some appear to be universal, occurring in virtually all taxa of organisms and types of environments. They offer clues to underlying mechanisms that powerfully constrain biodiversity. We describe recent progress and future prospects for understanding the mechanisms that generate these power laws, and for explaining the diversity of species and complexity of ecosystems in terms of fundamental principles of physical and biological science.

Ecosystem↗
PubMed2002

Effects of size and temperature on developmental time.

Body size and temperature are the two most important variables affecting nearly all biological rates and times. The relationship of size and temperature to development is of particular interest, because during ontogeny size changes and temperature often varies. Here we derive a general model, based on first principles of allometry and biochemical kinetics, that predicts the time of ontogenetic development as a function of body mass and temperature. The model fits embryonic development times spanning a wide range of egg sizes and incubation temperatures for birds and aquatic ectotherms (fish, amphibians, aquatic insects and zooplankton). The model also describes nearly 75% of the variation in post-embryonic development among a diverse sample of zooplankton. The remaining variation is partially explained by stoichiometry, specifically the whole-body carbon to phosphorus ratio. Development in other animals at other life stages is also described by this model. These results suggest a general definition of biological time that is approximately invariant and common to all organisms.

Amphibians↗
PubMed2002

Allometric scaling of metabolic rate from molecules and mitochondria to cells and mammals.

The fact that metabolic rate scales as the three-quarter power of body mass (M) in unicellular, as well as multicellular, organisms suggests that the same principles of biological design operate at multiple levels of organization. We use the framework of a general model of fractal-like distribution networks together with data on energy transformation in mammals to analyze and predict allometric scaling of aerobic metabolism over a remarkable 27 orders of magnitude in mass encompassing four levels of organization: individual organisms, single cells, intact mitochondria, and enzyme molecules. We show that, whereas rates of cellular metabolism in vivo scale as M(-1/4), rates for cells in culture converge to a single predicted value for all mammals regardless of size. Furthermore, a single three-quarter power allometric scaling law characterizes the basal metabolic rates of isolated mammalian cells, mitochondria, and molecules of the respiratory complex; this overlaps with and is indistinguishable from the scaling relationship for unicellular organisms. This observation suggests that aerobic energy transformation at all levels of biological organization is limited by the transport of materials through hierarchical fractal-like networks with the properties specified by the model. We show how the mass of the smallest mammal can be calculated (approximately 1 g), and the observed numbers and densities of mitochondria and respiratory complexes in mammalian cells can be understood. Extending theoretical and empirical analyses of scaling to suborganismal levels potentially has important implications for cellular structure and function as well as for the metabolic basis of aging.

Animals↗