Damage Response/Recovery in Health

When the biological system encounters some sort of stress, compensation recovery systems kick in to protect the body. Once damage is done, damage recovery response is engaged. While many compensatory mechanisms are immediate and comprise mainly reflexes involving the nervous system and pre-formed hormones(neurotransmitters) and mediators, prolonged stress and damage response will involve growth factor or nucleus-acting hormone release, priming, and genetic involvement in the synthesis of effector proteins for long-term adaptation. Increased cyclic AMP fuels metabolism, needed for stress, until exhaustion of nutrients sets in.

Gene regulation involves epigenetic modification, and feed-back(end-product) inhibition. There is up-regulation of heat-shock protein to fold proteins(in endoplasmic stress), anti-oxidants (in oxidative[phosphorylation] stress), immune response in infections, autophagy, repairs and apoptosis. Hence, small or transient amounts of stress will prompt the damage recovery response, even as damage is not obvious.

Limited resources(from exhaustion and low supplies), in times of stress, will increase metabolism through increased AMP and eventually activate Sirtuins. This prompts de-acylation of fats and de-acetylation of histones and DNA. Preferentially, repair genes remain acetylated and upregulated and more stem cells are made, even if slowly, and accumulate and only just pro-differentiate waiting for increased nutrition to eventually differentiate. Sirtuins levels increase in response to increased NAD/DADH ratio, a sign of stress(oxidative, nutritional and endoplasmic reticulum). They are a major activator of stress response.

The endosome membrane also senses free radicals(nutritional stress) and prompts autophagy, promoting the pentose-5-P pathway(nutritional stress)that promotes anti-oxidation(glutathione) and proliferation of stem cells.

However, in the long run, chronic, severe damage, leads to down-regulation, exhaustion of these damage recovery systems or irreparable free radical damage and will result in disease. Normally, good response is one that is transient, allowing for the recovery of the recovery system, itself. We see this with physiological, hormonal response which follows a rhythm, itself embedded within the circadian rhythm, having different activities of different organs occurring at different times and keeping pace with the limited energy supplies for efficient functioning of the body. A system in overdrive is bound to self-destruct and fail as metabolism is perturbed. Pathogens will use this attribute to insert porins in, and toxins through, the membranes of host cells to scramble metabolism and permit infections.

Dr. Oliver Verbe Birnso, MD

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