Unified nutritional and molecular mechanisms

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Endogenous Hydrogen Sulfide Production Is Essential for Dietary Restriction Benefits

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Excerpt: “…unifying nutritional and molecular mechanisms remain elusive.”

Reported as

Molecular mechanism behind health benefits of dietary restriction identified

Excerpt 1) “Dietary restriction is a type of intervention that can include reduced overall food intake, decreased consumption of particular macronutrients such as protein, or intermittent bouts of fasting. It is known to have beneficial health effects, including protection from tissue injury and improved metabolism. It has also been shown to extend the lifespan of multiple model organisms, ranging from yeast to primates.”
Excerpt 2) “The investigators also found that genes involved in H2S production were also required for longevity benefits of dietary restriction in other organisms, including yeast, worms, and flies.”
My comment: Their journal article imagery links yeasts, worms, and flies to mice. The news report links “…multiple model organisms, ranging from yeast to primates.” The links to cell type differentiation can be viewed in the following context.
Biological energy comes from the sun. The sun’s energy links light-induced amino acid substitutions in plants and animals to nutrient-dependent amino acid substitutions. Nutrient-dependent amino acid substitutions differentiate all cell types of all individuals of all species in this series of RNA-mediated events:
1) Nutrient-dependent food energy links RNA-directed DNA methylation to feedback loops.
2) The feedback loops link food odors and pheromones to the RNA-mediated physiology of reproduction via conserved molecular mechanisms of energy-dependent protein folding.
3) The conserved molecular mechanisms of protein folding link the epigenetic landscape to the physical landscape of DNA in the organized genomes of all species.
In the context of anything known about the role of amino acids, the claim that “…unifying nutritional and molecular mechanisms remain elusive” is preposterous. That claim ignores everything known about nutrigenomics and pharmacogenomics, which link metabolic networks to genetic networks via conserved molecular mechanisms that are bio-physically constrained by the chemistry of protein folding in species from microbes to man.
For example, their slide imagery links ecological variation in yeasts to nematodes, flies, and the mouse model of nutrient-dependent pheromone-controlled ecological adaptations. We detailed the role of RNA-mediated cell type differentiation from yeasts to mammals in our 1996 Hormones and Behavior review, and I provided several more across-species examples of RNA-mediated ecological adaptations in my 2013 review, which extended the mouse model to humans via one base pair change and a single amino acid substitution.
Nothing known about the physics, chemistry, or molecular epigenetics of cell type differentiation has changed since 1996. Everything known unifies nutritional and molecular mechanisms from hydrogen atoms to ecosystems. However, nothing currently known about anything supports use of de Vries definition of ‘mutation’ or assumptions that mutations could somehow lead to increasing organismal complexity manifested in the morphological and behavioral phenotypes of species from microbes to man. For contrast, Schrodinger wrote: “…there are no intermediate forms between the unchanged and the few changed. De Vries called that a mutation. The significant fact is the discontinuity. It reminds a physicist of quantum theory -no intermediate energies occurring between two neighbouring energy levels. He would be inclined to call de Vries’s mutation theory, figuratively, the quantum theory of biology.  We shall see later that this is much more than figurative. The mutations are actually due to quantum jumps in the gene molecule.” — What is Life?: With Mind and Matter and Autobiographical Sketches (p. 33-34).
Do the authors of the review on dietary restriction think that “…unifying nutritional and molecular mechanisms remain elusive” because they are trying to unify them in the context of pseudoscientific nonsense? Do they think that claims about mutations and evolution have been supported by experimental evidence of biologically-based cause and effect at any time since the Modern Synthesis first became popular? I think the popularity of neo-Darwinism may be attributed to the fact that belief in theory reduces the amount of established experimental evidence from physics, chemistry, and molecular biology that must be understood and integrated.
Simply put, those who believe in Mutation-Driven Evolution can dismiss accurate representations of how ecological adaptations occur in the context of an atoms to ecosystems model: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems.
Instead of linking hydrogen atoms across all ecosystems via the conserved bio-physically constrained chemistry of protein folding in the context of Feedback loops [that] link odor and pheromone signaling with reproduction, and Signaling Crosstalk: Integrating Nutrient Availability and Sex, “The mechanism by which one signaling pathway regulates a second [that] provides insight into how cells integrate multiple stimuli to produce a coordinated response” is reduced to the claim that: “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world (Nei, 2013, p. 199).”
That claim is based on the definition of ‘mutation’ by Hugo de Vries. His definition led to the assumption that unexplained jumps in energy could be linked from changes in base pairs via mutations linked to amino acid substitutions. Claims that amino acid substitutions are mutations have since extended the pseudoscience associated with use of de Vries definition of ‘mutation’ and the use of assumptions in attempts to explain how biodiversity arose. In what may be an unending series of ridiculous claims based on definitions and assumptions, the most recent extension of unsupported assumptions was reported in Evolution of oligomeric state through allosteric pathways that mimic ligand binding.
Excerpt: “The most likely hypothesis is that these mutations act by changing either protein conformation or conformational dynamics, analogous to the ways in which allosteric ligands introduce conformational change. Thus, we referred to the indirect mutations as allosteric mutations.”
My comment: These authors use de Vries definition of ‘mutation.’ They ignore the need to link biological energy from the sun to ecological adaptations via bio-physical constraints on the chemistry of protein folding. Moving forward in the context of their ignorance, they introduce the term ‘allosteric mutation’ in an attempt to explain the evolutionary inferences they have already made.
No explanatory power ever was attributed to the term ‘mutation.’ Can any explanatory power be attributed to allosteric mutations? Others now seem to be suggesting that allosteric mutations may contribute to Epistatic Adaptive Evolution of Human Color Vision.
Excerpt 1) [Their] “…observations imply that the mechanisms of epistatic interactions must be understood by studying various orthologues in different species that have adapted to various ecological and physiological environments.”
My comment: In my model, ecological adaptations are nutrient-dependent and controlled by the physiology of reproduction, which links the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man. Amino acid substitutions are linked from theromodynamic cycles of protein biosynthesis and degradation to the stability of protein folding and organism-level thermoregulation.
Excerpt 2) For comparison, they claim that “The blue-sensitive visual pigment in human (human S1) evolved from the UV-sensitive pigment in the Boreoeutherian (or Boreotherian) ancestor (AncBoreotheria S1) by seven mutations.”
Excerpt 3) As if any of their claims was based on biological facts, they add that “Trichromatic color vision in the human lineage was fully developed by 30 My ago by interprotein epistasis among the three visual pigments.”
No experimental evidence of biologically-based cause and effect supports that claim. Nothing known about interprotein epistasis suggests it occurs in the context of mutations during any evolutionary event that might otherwise link amino acid substitutions to interprotein epistasis in any organism in 30 million years or in 3.5 billion years. Instead, we read in A universal trend of amino acid gain and loss in protein evolution that “We cannot conceive of a global external factor that could cause, during this time, parallel evolution of amino acid compositions of proteins in 15 diverse taxa that represent all three domains of life and span a wide range of lifestyles and environments. Thus, currently, the most plausible hypothesis is that we are observing a universal, intrinsic trend that emerged before the last universal common ancestor of all extant organisms.” Interpretation: If no global external factor links the parallel evolution of amino acid compositions across all three domains of life, the only thing left is an internal link from metabolic networks to genetic networks. The link begins with biological energy and light-induced amino acid substitutions that differentiation cell types in plants and animals.
No experimental evidence of biologically-based cause and effect links any claims about mutations from the epigenetic landscape to the physical landscape of DNA via what is believed about the biological energy that comes from the sun. That energy, links light-induced amino acid substitutions to nutrient-dependent pheromone-controlled ecological adaptations in species from microbes to man in the context of what is known about nutrient-dependent amino acid substitutions and the experience-dependent de novo creation of olfactory receptor genes.
The de novo creation of olfactory receptor genes is beneficial. Dots represent amino acid differences with respect to the genome reference, not an inferred ancestor.
Mutations that lead to the loss of olfactory receptor genes are detrimental. “orco mutant olfactory sensory neurons have greatly reduced spontaneous activity and lack odour-evoked responses.”
Invertebrates exemplify the role that the nutrient-dependent pheromone-controlled physiology of reproduction plays during the development of their morphological and behavioral phenotypes. “Structural and cladistic analyses resolve an ancestral ground pattern common to all investigated taxa: chemosensory afferents supplying thousands of intrinsic neurons, the parallel processes of which establish orthogonal networks with feedback loops, modulatory inputs, and efferents.”
Vosshall’s group has “…established a clear genetic association between such changes and behaviour. This work begins to unravel the molecular genetic basis of an important evolutionary shift in insect host preference. More generally, such host shifts not only impact the efficiency of mosquitoes as vectors of infectious disease, but contribute to the economic damage caused by agricultural pests49 and play a key role in the formation of new species50.”
Simply put, Vosshall’s works link odor-induced nutrient-dependent de novo creation of olfactory receptor genes to the formation of new species via the bio-physically constrained chemistry of protein folding that enables the de novo creation ot the olfactory receptor genes. See: The activity-dependent histone variant H2BE modulates the life span of olfactory neurons.
Excerpt: “How do the five amino acid differences between H2BE and H2B convey such distinct functional attributes? Studies of H3.3, a histone variant that differs with canonical H3 by merely four amino acids and that plays a critical role in embryonic development and gene expression in adulthood, illustrate how small sequence variations in histones can generate distinct functions (Elsaesser et al., 2010).”
The unanswered question arises: “How much nutrient energy is required to link a base pair change to an amino acid substitution?” It may be less energy than can be measured. Nevertheless, fixation of amino acid substitutions occurs. My point is fixation of the amino acid substitutions in new genes occurs in the context of nutrient-dependent pheromone-controlled ecological adaptations. That is how the stability of the genome in generation after generation is virtually ensured. Nutrient-energy can best be used to add to existing organismal complexity manifested in the morphological and behavioral phenotypes of species from microbes to man. None of that extant diversity appears to have evolved via mutations in any species from yeasts to primates. There may be no such thing as a beneficial mutation unless benefit is defined and mutation is defined to make people think the term beneficial mutation can be used in the context of protein structure and function.
Loss of Olfactory Receptor Genes Coincides with the Acquisition of Full Trichromatic Vision in Primates.
Loss of genes due to mutations is expected in the context of everything known about how ecological variation leads to ecological adaptations via nutrient-dependent cell type differentiation in all genera. Mutations perturb protein folding, which is manifested in pathology when mutations accumulate. The accumulation of mutations does not lead to the creation of new genes.
Nutrient-dependent amino acid substitutions are associated with the de novo creation of olfactory receptor genes. Mutations are associated with the loss of genes from organized genomes after the organized genome is stabilized by amino acid substitutions in DNA via the epigenetic effects of food odors and pheromones. Each species has the number of genes it requires to survive, which include some genes or pseudogenes that enable ecological adaptations to unsuspected ecological variation. This is exemplified in the context of eye regression in cave fish. Even the complexity of the eye is adapted when the nutrient poor ecology of a dark cave forces the fish to adapt. It becomes blind because only the sense of smell is required to find food and to reproduce.
I’ve addressed the problems with evolutionary theory repeatedly in the context of epigenetic pharmacology, which is also called pharmacogenomics, and in the context of human senescence. In the mid-1990’s I presented twice at anti-aging medicine conferences held in Las Vegas, Nevada. I still see the same nonsense being touted and refuted two decades later.

Beta-Amyloid: The Emperor Really Does Have No Clothes

Excerpt 1) : “By 2012 we had several huge Phase 3 trials with a couple of different anti-amyloid antibodies from different companies – and a slew of negative data.
What happened next was very interesting.
Instead of drawing the obvious conclusion (that the amyloid hypothesis was false), the assembled masses began casting around for a different explanation for the surprising failure.”
My comment: The conclusion from my 2012 review was: “Socioaffective neuroscience and psychology may progress more quickly by keeping these apparent facts in mind: Olfaction and odor receptors provide a clear evolutionary trail that can be followed from unicellular organisms to insects to humans (Keller et al., 2007; Kohl, 2007; Villarreal, 2009; Vosshall, Wong, & Axel, 2000).”
Excerpt 2)  “Biology is complex enough that there is always wiggle room – you can never prove that a hypothesis is wrong, only that it is increasingly unlikely to be true.”
In an earlier work, Mitchell’s group linked what is known about amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR to the human ability to detect species-specific differences and fat acid content via the sense of smell. See: Detecting Fat Content of Food from a Distance: Olfactory-Based Fat Discrimination in Humans.
I’ve probably posted several times to this blog site about the olfactory prowess of humans at the same time others have continued to claim that we are microsmatic. My thoughts are scattered and I’ve been spending more time attempting to discuss current works on cell type differentiation, but appear to be wasting time on biologically uninformed science idiots. They are everywhere. See for example:

Origin of the Eukaryotic cell: Part II – Cytoskeleton, membranes, and beyond

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