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Med Hypotheses. 2007;69(5):1147-53. Epub 2007 Apr 18.

How dietary restriction catalyzed the evolution of the human brain: An exposition of the nutritional neurotrophic neoteny theory.

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Amenta Press Inc., P.O. Box 236, Damascus, MD 20872, USA.


The purpose of this theoretical treatise is to explain the evolution of human encephalization. The evolutionary expansion of the human brain is herein regarded as a single component of an interrelated complex encompassing depressed somatic and sexual development and increased longevity. These cardinal phenotypic features, termed the Quadripartite Complex, were selected for their adaptiveness amidst the environmental deterioration extant during the formative phase of human evolution--the Plio-Pleistocene period. This interval of environmental transformation inevitably eventuated in ecological alteration and dietary diminution. Suggestively, experimentally imposed dietary restriction routinely results in lengthened lifespan, delayed sexual maturation, depressed growth and increased encephalization as a concomitant consequence of body mass reduction and brain mass maintenance. Thus, dietary restriction ostensibly induces discernible metabolic adaptations whether incurred ontologically or evolutionarily. Several experiments indicate that dietary restriction promotes the preservation and generation of neurons via induction of neurotrophic factors. To the extent that neurogenesis is a molecular mediator of mental acuity, it is evident that nutrition and cognition are intimately linked. Extrapolating to an evolutionary context, increased intelligence ought to confer advantages to organisms enduring dietary deprivation insofar as increased intelligence ensures more facile food acquisition. This reasoning underlies the nutritional neurotrophic neoteny (N(3)) theory, which holds that humans exhibit an altered pattern of neurotrophin expression resulting from positive selection for heightened intelligence amidst environmental deterioration and consequent dietary deficiency. The altered pattern of neurotrophin expression exhibited by humans, it is deduced, results in a protracted phase of developmental neurogenesis and a resultant retention of neurons that would otherwise be extirpated due to programmed cell death. Importantly, during neonatal neurogenesis mammals produce an excess number of neurons whose eventual destruction is dictated by neurotrophic factors. An altered pattern of neurotrophin expression during neurogenesis, as N(3) proposes, could therefore furnish a larger adult brain. As to how humans could afford to accrete exuberant neural tissue under conditions of chronic food scarcity the homo hypothalamic hypometabolism (H(3)) theory offers a plausible answer: reduced growth and delayed sexual maturation, mediated by the hypothalamus and its endocrine effectors, offset the energetic costs of increased encephalization in humans. H(3) is herein presented as a general theory of human evolution while N(3) may be regarded as a special theory of human encephalization.

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