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I.R.F. / Aging news / General / 06062801

The Anti-stress, Anti-impairment and Anti-aging Therapy for the Brain
Posted on: June 28, 2006

A new direction in anti-aging medicine is the long-term administration of nutraceuticals (functional foods) coupled with regenerative bioactive factors. In conformity with their main objectives, these therapies may do one or more of the following: (i) decelerate, antagonize, and remove the "causes of aging," as well as diversify, improve, and efficiently increase the "causes of longevity"; (ii) have anti-stress, anti-impairment, and anti-aging actions;4 and (iii) synergistically protect, regulate, and recover the three key organs (liver, heart, and brain) of the human being. In anti-aging medicine, the role, characteristics, and functions of the brain determine specific objectives in order to:

  • optimize the unbalanced neurono-glial homeostasis, especially by anti-inflammatory and anti-degenerative actions;
  • restore the balance between oxidative stress damage and antioxidant defense–repair processes;
  • ensure mitochondrial protection and remove oxidative mitochondrial decay;
  • reconfigure and intensify the functions of catabolic subcellular systems and accelerate destruction and elimination of subcellular garbage;
  • increase ribosomal RNA and protein biosynthesis, as well as activate polyribosomes and endoplasmic reticula; and
  • protect and offer repair potential for genome damage.

One of the main factors in proteasome – lysosomal aging dysfunction is progressive accumulation and storage of brain lipopigments (LPs). Cerebral LPs – lipofuscin and ceroid – represent a significant marker in postmitotic normal and pathologic aging. Moreover, LPs are connected with important causal and associated neuropathologic damage, generating imbalances in neuronal and glial homeostasis and multiple subcellular impairment, with negative consequences ranging from neuronal function to brain physiology. Therefore, LP processing, lysis, and elimination can become the main mechanisms for the reestablishment of metabolic, cellular, and tissue homeostasis, as well as in anti stress, anti-aging, and rejuvenation therapies. However, in rejuvenation therapies, these important anti-aging mechanisms are and should be prefigured and followed by other synergistic subcellular revitalizing actions, mechanisms, and effects.

Processing, Lysis and Elimination of Brain Lipopigments

The anti stress, anti-impairment, and anti-aging therapy (3A-SIA-T) under consideration corresponds to these objectives and acts at the neuronal subcellular level. 3A-SIA-T is a simultaneous synergistic neurometabolic neurovascular medication with the following complementary composition:

  1. for anabolic rejuvenation: Hydrooxopyrimidine carboxylates/oxopyrrolidine acetamides (18.8–20.0%), fructose (0.6–0.7%), nicotinic alcohol/acid/amide with prolonged release (4.1–5.3%), lithium (0.025–0.033%), potassium (2.5–2.9%), magnesium (0.3–0.4%), iodide (0.005–0.007%), and monoacide phosphate (2.6–3.5%);
  2. for catabolic homeostasis and garbage scavenging and elimination: Aminoethanol phenoxyacetates/aminoethyl phenoxyacetamides (31.0–33.1%), methionine (18.0–19.1%), aspartate (9.7–10.6%), fructose (1.1–1.3%), vitamin B1 (0.9–1.3%), vitamin B6 (1.2–1.5%), nicotinic alcohol/acid/amide with fast release (1.1–1.3%), magnesium (1.2–1.5%), zinc (0.3–0.7%), and sulfate (0.5–1.0%).

Brain Metabolic Pathways and Longevity

Two main metabolic pathways of the nervous tissue with the same course, but in the opposite directions, are used in glia–neuron nutrition and metabolism, as well as by rejuvenation therapies. They are: (i) import pathway: arterioles – capillaries → glial cells → neurons, and (ii) elimination pathway: neurons → neuroglial systems → capillary-venule areas.

First, the regenerative neuroactive factors of 3A-SIA-T activate arteriolar precapillary and capillary areas, and improve neuron supply from plasma with anabolites, specific nutrients, and nutraceuticals, and thus better nourish the nerve cells. Then, by acting on neuroglia, they ameliorate glial functions; destroy, dissociate, and dissolve glial LP conglomerates by glioplasm rehydration and glial LP-lytic actions; and optimize glial–neuronal interactions.
In neurons, 3A-SIA-T compounds have the following effects:

  • enhancing the antioxidative defense and having anti-LP-genesis actions, through their scavenging properties;
  • increasing the ribosomal RNA, total RNA, water-soluble proteins, and total proteins, stimulating brain anabolism;
  • protecting and augmenting the number of healthy mitochondria and supporting energetic metabolism; and
  • regulating proteasome–lysosomal dysfunction and enzymes by neuroplasm rehydration and initiating the break-up of the stored neuronal aggregated LP, followed by LP vacuolation, disintegration, and decrease, and a reduction of water-insoluble proteins.

Second, in neurons, diminished processed LPs are carried by intracellular transport in the neurosomal periphery. Neurono-glial transfer of processed LPs is initiated by activation of circumscribed neurono-glial areas. Then, possibly by localized exo-endocytosis between neurons and adjacent glia (especially parenchymal microglia), the intercellular transfer of the neuronal LPs can be realized. Thus, therapeutically activated glia (particularly microglia) turn into brain garbage collectors and transporters, moving waste from neuronal proximity, through neuropil, to pericapillary areas. Thus, the microglial paradox appears, that is, cells with a high rate of division have their cytoplasm filled up to 90% with LPs. An explanation for this is the glial mechanism of neuronal LP collecting and transport, besides the phagocytosis with degradation of neuronal apoptotic bodies. Therapeutic processing of glial LPs increases in the capillary neighborhood.

Finally, the vacuolated and highly processed LPs (glial end-feet, pericytes, perivascular microglia) are transferred from pericapillary zones into capillaries and venules (postcapillary areas), and eliminated together with catabolites in capillary lumina. The natural impaired and incomplete mechanism of LP transport and elimination is therapeutically reorganized into an activated, complete, and efficient mechanism.

In the brain, 3A-SIA-T compounds exert their rejuvenative actions and LP processing and lysis by a metabolic route from capillaries through neuroglial cells to neurons. In addition, this simultaneous synergistic anti-stress and anti-aging therapy also activates the inverse pathway, in which the highly processed LPs are moved, transported, and eliminated from neurons into capillary lumen via glial systems. Moreover, long-term administration of neuroactive therapies having these synergistic rejuvenation mechanisms, actions, and effects represents new prospects in the deceleration of normal and pathologic cerebral aging, with increase of neuronal healthy longevity, as well as alternative and complementary treatments in neuro-psycho-geriatrics. Three different strategies for anti-stress, anti-aging, and rejuvenation have certain common molecular, cellular actions, mechanisms, and effects: (i) healthy diet, nutraceuticals, regenerative bioactive factors, (ii) regular exercise, daily physical activity, and (iii) hormesis, including low-level stress. Their association produces synergistic, amplified, and consolidated effects and represents an efficient direction in anti-aging prophylaxis, therapy, and recovery, as well as in sanogenesis and prolongevity medicine.

Source: Sorin Riga, Dan Riga, Francisc Schneider, and Florin Halalauc; Processing, Lysis, and Elimination of Brain Lipopigments in Rejuvenation Therapies; Ann. N.Y. Acad. Sci. 1067: 383–387 (2006).
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