Epigenetic regulation of aging by glycine and GnRH

By: James V. Kohl | Published on: May 26, 2015

Summary:  “…the regulation of two genes involved with the production of glycine, the smallest and simplest amino acid, is partly responsible for some of the characteristics of aging. This indicates that the aging process in the mitochondrion is controlled by epigenetic regulation, not by mutations.”
My comment: The broad-based extension of the fact that aging is epigenetically controlled, extends everything known about RNA-mediated cell type differentiation across the life history transitions of all genera. The focus here is on vertebrates, but the conserved molecular mechanisms extend across all species.
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Thanks to Teresa Binstock for alerting me to this. Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects
Excerpt:

Given that human aging can be seen as a consequence of a programmed phenomenon, it is possible that epigenetic regulation also controls human aging.

My comment:  See: Search Results for ‘glycine’ here at RNA-mediated.com and also Search Results for: glycine  in the “Science” section at Pheromones.com for additional information. It should become apparent why I started with the domain Pheromones.com in 1995 and linked nutrient-dependent RNA-mediated amino acid substitutions to cell type differentiation after addressing the control of nutrient-dependent reproduction. Others now realize that the physiology of reproduction biophysically constraints transgenerational epigenetic inheritance of morphological and behavioral phenotypes. The new information about the control of RNA-mediated cell type differentiation by pheromones and anti-aging medicine has been delayed for more than two decades by human pheromone-deniers and other pseudoscientists.
In 1994, for example: I presented “Olfactory-hormonal relationships in learning, memory, aging, and behavior” during the “2nd Annual Conference on Anti-aging Medicine & Biomedical Technology for the year 2010” and in 1995, I presented “Olfactory-genetic-neuronal-hormonal reciprocity in learning, memory, behavior and in immune function” at the “3rd Annual Conference on Anti-aging Medicine & Biomedical Technology for the year 2010.”
Teresa Binstock’s prescient contributions on RNA-mediated cell type differentiation in our 1996 Hormones and Behavior review article led me to examine the role of achiral glycine in vertebrates. See: From Fertilization to Adult Sexual Behavior
Excerpt:

Evolutionary conservation, both of pheromonal communication and its importance to behavior, is indicated by the involvement of a key mammalian reproductive hormone. For instance, a yeast pheromone, the alpha-mating factor, is very similar in structure to mammalian gonadotropic releasing hormone (GnRH). When injected into rats, this chemical binds to pituitary GnRH receptors and brings about the release of LH. Loumaye, Thorner, and Catt (1982) note: “GnRH and the yeast alpha-mating factor appear to represent a highly conserved effector system which includes the peptide ligand, the cell-surface receptor, and the physiological regulation of reproductive function” (p. 1325).

My comment: Substitution of the only achiral amino acid in the GnRH decapeptide of vertebrates links the light-induced de novo creation of glycine and other amino acids to the nutrient-dependent pheromone-controlled behaviors of species from microbes to humans. One need only consider that fact in the context of what is currently known about the biophysically constrained chemistry of RNA-mediated amino acid substitutions and protein folding in all genera.
1994 Abstract

The early prenatal migration of gonadotropin releasing hormone (GnRH) neurosecretory neurons appears to enable a neuroendocrine sequence of events that allows human pheromones to influence postnatal GnRH secretion, maturation of the hypothalamic-pituitary-gonadal axis; and, in part, the hypothalamic-pituitary-adrenal axis; hormone-dependent synaptogenesis and synaptolysis; neurotransmission; learning; memory; and behavior. That GnRH regulates the collective neural output manifest in reproductive behavior seems consistent with effects of drug therapies that influence the GnRH pulse, and which are used to treat disorders of neuroendocrine and reproductive maturation as well as dysfunctional behaviors. Is the hypothalamic GnRH pulse generator both the biologic and the psychologic core of mammalian reproduction? What is the contribution of extrahypothalamic GnRH? Is there a lack of “hard” scientific evidence for relationships between biologically relevant odors, olfaction, aging, and human behavior?

1995 Abstract

A five-step pathway allowing the social environment (“nurture”) to influence the genetic substrates (“nature”) of mammalian behavior is: gene->cell->tissue->organ->organ system. Though there are many environmental influences on the first step of this pathway, odors are the only known social-environmental stimuli that appear to activate gene expression in neurosecretory cells of tissue in the brain an organ that is essential to any organ system involved in learning, memory, and behavior. Olfaction appears to influence learning, memory, and behavior. Thus, the production and distribution of human odors may link two aspects of our social environment (e.g., olfaction and odors) to the genetic substrates of our behavior through a five-step pathway common to many other vertebrates. Olfactory input influences the gonadotropin-releasing hormone (GnRH)-directed regulation of gonadal and adrenal steroidogenesis. Thus, olfactory deficits associated with aging may be linked to a need for hormone replacement therapy, including dehydroepiandrosterone (DHEA). Similarly, olfactory deficits may be linked to immune system function. Many other hormones/neurotransmitters (e.g., melatonin and dopamine) feed back on the GnRH neuronal pathway. This pathway appears to be both the biological and the psychological core of mammalian, including human, behavior. Thus, the influence of odors and olfaction on levels of hormones, including neurotransmitters, may be linked to age-related changes in learning, memory, behavior, and immune system function.

2015

Scientists reverse aging in human cell lines and give theory of aging a new lease of life

Excerpts:

…the regulation of two genes involved with the production of glycine, the smallest and simplest amino acid, is partly responsible for some of the characteristics of aging.This indicates that the aging process in the mitochondrion is controlled by epigenetic regulation, not by mutations.

See for comparison: Mutation-Driven Evolution
Concluding sentences:

“In other words, genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world. In this view of evolution there is no need of considering teleological elements” (p. 199).

See for comparison: Nutrient-dependent/pheromone-controlled adaptive evolution: a model

Concluding paragraph:

Unconscious affects that are manifested during the development of diversified life and human behavior are, by their very nature, part of life that few people think about (Kohl et al., 2001). Therefore, the largest contributor to the development of our personal preferences may be the unconscious epigenetic effects of food odors and pheromones on hormones that organize and activate behavior. If so, the model represented here is consistent with what is known about the epigenetic effects of ecologically important nutrients and pheromones on the adaptively evolved behavior of species from microbes to man. Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.

My comment: All accurate representations of biologically-based cause and effect have consistently shown that there are no other factual representations of epigenesis and epistasis that can be compared to my model.  The most recent report on glycine and cell type differentiation during the life history transitions of vertebrates also suggests that the honeybee model organism links nutrient-dependent base pair substitutions in yeasts to the RNA-mediated amino acid substitutions in vertebrates that differentiate nutrient-dependent pheromone-controlled cell types via the conserved molecular mechanism that Teresa Binstock detailed in the “molecular epigenetics” section of From Fertilization to Adult Sexual Behavior.

See also for comparison to published works by JW Locasale: Nutrient-dependent/pheromone-controlled adaptive evolution: a model
Excerpt:
Disease is associated with mutations exemplified in cancer where perturbations of the glucose-dependent thermodynamic/thermoregulatory equilibrium are equally clear (Locasale, 2012).

Excerpt:

Reprogramming of gene expression in elderly fibroblasts occurred in GCAT (Fig. 3b), which regulates glycine production in mitochondria17, 18. It was therefore likely that reduced glycine production in mitochondria by epigenetic downregulation of GCAT (Fig. 3a) resulted in the age-associated respiration defects (Fig. 1a).

My comment: Reference 17, is Locasale, J. W. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat. Rev. Cancer 13, 572583; doi:10.1038/nrc3557 (2013).
The barrage of pseudoscientific nonsense touted by evolutionary theorists and their idiot minions continues to test the patience of anyone who challenges ideas about cell type differentiation that link mutations to pathology and to aging, and RNA-mediated amino acid substitutions to health and longevity in all genera.
See for examples of nonsense touted by the biologically uninformed:
In evolution, ‘house of cards’ model wins
Tiny spheres of human cells mimic the brain, researchers say
Our bond with dogs may go back more than 27,000 years
John Glenn: Evolution should be taught in schools


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