BiTherapca Health

Type 2 diabetes is recognized as a complication of  metabolic syndrome, which is a cluster that includes hyperlipidemia, hypertension, increased body fat around the waist, and an increased blood sugar, believed to be a result of oxidative stress. A ketogenic diet decreases glucose tolerance, at least temporarily. Fats do not need insulin to get into tissues nor do they particularly stimulate the mTOR pathway. Hence, like fasting, they stimulate the AMP kinase that promotes autophagy, and so produce a better mitochondrial function.It has been postulated that the inhibition of histone deacetylase is the underlying mechanism for this effect.  A decreased ATP:AMP ratio is a sign of energy exhaustion or low supplies, and stress, that activate AMPK, comparable to the activation of sirtuins by a decreased NADH:NAD ratio which deacetylates macromolecules post-transcriptionally, thus activating these molecules.These effects activate repairs of worn out cells, including stem cells....

It is clear that infections, and especially chronic ones that are intracellular, lead to cellular senescence and eventually to biological aging of the individual. Senescence in one cell begets senescence in the other and the domino effect spreads around the body just like prions spread, if phagocytsis does not clear the defective cells. In fact, this is easily mediated by amyloids, if not by inflammatory mediators produced by senescent cells themselves. Dealing with senescence has been most challenging from the medical point of view. However, advances in research are yielding fruits. It has been found that senescent cells are produced due to mild stress that allows the cells to mount a chronic damage response, involving P53, HSP with protein misfolding response that includes protein folding, autophagy and some repair. It is only when autophagy is overwhelmed, that senescence sets in, in full gear. The cell stops growing. Research has shown that senescent cells become resistant to...

C hronic infections(intr acellular through phagocytosis or macrophagy) prompt autophagy( self-eating) and ubiquitin/proteosome degradation due to stress or damage incurred. Autophagy maintains DNA stabilty.  Chaperone-mediated autophagy recognizes, binds, unfolds then transports damaged components to lysosomes. Hsp 70(heat shock protein 70) carries out this function.  In microphagy, invaginations and protrusions in lysosomes trap substrates--proteins, mitochondria, peroxisomes, lipid droplets. Hsp 70 action, here, in microphagy, does not require the unfolding of the substrate as opposed to its action in the chaperone-mediated autophagy. M itophagy is microphagy involving the mitochondria. We also have pexophagy, ER-phagy, ribophagy and lipophagy. Macro(auto)phagy needs the double membrane autophagosomes. Xenophagy is a macrophagy and recognizes microbes and ubiquitinates them. Bacteria in damaged phagosomes/phagolysomes are ubiquitinated by recognition of carbohydrates i...

Nuts, whole grains, beans, fruits, vegetables are all rich in biogenic 1,3/1,4  polyamines, namely spermidine, spermine and putrescine, which, known to stabilize the DNA, improve the circadian rhythm, regulate metabolism, prevent aging and prolong healthspan. They do so, by decreasing enhanced DNA methylation, a marker seen in aging and known to be transmitted through generations of progenies. Polyamines do so, by taking up and owning the methyl group and sparing the methyl group attachment to the DNA base pairs. In fact, cancer and senescent cells grow and survive partly due to high levels of polyamines they possess. Adult mast cells store cationic polyamines in their granules, attched to sulfated heparan, and  proliferate partly due to them, as well as a result of expressing the stem cell factor(SCF)  receptor, c-KIT. SCF ligand is mostly supplied by fibroblasts and endothelial cells in the niche. All human cells posses these polyamines, biosynthesized from amino acid...

It is becoming more and more clear that the living cell via its genome is aware of and senses its environment and adjusts(adapts) to it. The environment, on its own part, affects the genes directly through mutations or indirectly, by modifying their expression, epigenetically in a physical or steric alteration of the heterochromatin and euchromatin, and with the introduction of chemical tags on genes through, for example, DNA methylation and acetylation. The genome senses itself through its sensing genes and their proteins, and makes the necessary adjustments to sustain life, by correcting damage done or adopting new 'lifestyle' if damage is permanent but not lethal. Genes exposed to the outer environment are not expressed because of the influence of inhibitory factors from without, while the inner ones, shielded from such influences, are expressed. These sensors equally determine species body architecture. The master gene which determines the body plan binds many transcrip...

Energy supply is the driver of metabolic activities and sustainability of life. It is no surprise, therefore, that development, growth, mental and physical acivities all rely on an adequate, ready-to-use energy source, the ATP. Since the mitochondrion is the major source of this, its well-being lies at the root of optimal body function and its poor state at the heart of most diseases. Mitochondrial gene expression is conditioned by the peroxisome proliferation genes, driven by factors such as, fibrate drugs, free fatty acids and arachidonic acids. Peroxisome activated receptors form heterodimers with vitamins A and D receptors. It goes without saying that any stress, such as sudden nutritional overload from food intake; exercise, fasting, with energy exhaustion or low supplies that call for mobilization from stores, activates the peroxisome proliferator-activated receptor, increases mitochondrial function and promotes metabolism. The receptors are nuclear genes that upregulate mitoch...

HUMAN CELL Classically, a senescent cell--one that no longer divides-- will have resulted when a stem cell had undergone multiple cell divisions, which events are generally accompanied by the shortening of the telomere, a biological clock marker of cellular aging. Cellular senescence is a physiologically irreversible growth arrest process that occurs when division-prone(-competent) cells encounter oncogenic stress. In replicative senescence, the gradual loss of  DNA at the end of the chromosome(the telomere), by DNA polymerases initialing RNA rather than DNA prime strand during replication and the lack of telomerases in most cells to effect repair, generate persistent DNA damage response (DDR), a vain attempt to repair DNA damage. This necessarily calls for cell division arrest.  Premature senescence occurs following damage to the DNA by oxidative stress, endoplastic reticulum stress that prompts autophagy and heat shock response; through inflammation, toxins,  infec...