Healthy Developmental Stress
Niacin has been described as the 'Youth Pill'. Niacin and nicotinamide are converted to NAD which boosts lipid metabolism, directly reducing oxidative stress, with the resultant conversion to NADH, which has potent anti-oxidant and anti-inflammatory properties, though oxygen free radicals are produced along the way in the metabolic path. The irritant nature of niacin which produces prostaglandins(responsible for flushing) will additionally boost metabolism through increased calcium entry into the cell, will generate free radicals and promote inflammation in a dose-dependent manner.
Of interest, sirtuins(silent information regulator 2) proteins, protein deacetylators, cause the de-acetylation of acetyl-lysine residues, alongside the hydrolysis of NAD into O-acetyl-ADP-ribose, the deacetylated substrate and nicotinamide, which in an end-product inhibition manner blocks sirtuins activity. Exercise,fasting and niacin which generate NAD(the former two by oxidizing and exhausting stores of NADH, generate free radicals, promote sirtuins activity with increased gene regulation, stem cell renewal and growth. By altering(increasing) the NAD:NADH ratio (a metabolic indicator of free radical production), sirtuins activity is ramped up and deacetylation, including of histones, will promote 'embryonic' or youth pattern of gene expression and support stem cell renewal and even de-differentiation, hence repair and reversal of senescence. Mild oxidative stress is a by-product of and promotes NAD formation, which is a co-target substrate of sirtuins.
Sirtuins therefore are produced in response to mild metabolic(oxidative) stress due to increased NAD, the substrate of the sirtuins deacetylation which, like methylation(with the antioxidant, methionine as substrate) in the reduced environment of the embryo, regulates growth(promotes repair and cell division). Thus altered gene expressions in aging accompanied by high mitochondrial (dys)function, an 'end-point' cellular differentiated state, are re-conditioned and once more become more regulated, as sirtuins go into action, to effect efficient gene expression in repair and rejuvenation. RNA factors(proteins) that bind to and regulate pre-mRNA and determine splicing, will now generate heat shock proteins and other juvenile protein isoforms in the more regulated expression in milder stress. This is, as it were, a replica of what happens during prenatal development, in the mild stress and short-lasting free radical spikes that prompt counter-stress compensations in the restrictive developmental low oxygen womb environment.
Low oxygen tension promotes growth(repair and cell division) and this through gene regulation which further produces a more reduced environment that in turn favors gene regulation but high tension facilates cell differentiation(cellular aging or senescence). There is no better way to achieve gene regulation than through spurts of intensive metabolic activation that produce ATP from NADH and leave behind NAD for sirtuins to act upon in concert with deacetylation. This can be achieved with niacin, exercise and fasting, contrasting with more differentiated tissue that develops where oxygen tension is sustainably high, far away from blood vessels(due to high carbon dioxide acidity). Alternatively, blood vessels(less differentiated) develop farther away from the surface of the skin epithelium (more differentiated), which is in direct contact with the oxygen of air.
Resverastrol(a polyphenol antioxidant found in grapes, peanut, berries and cocoa) is a sirtuin 1 activator. Niacin taken with resverastrol clears most chronic infections due to restored gene expression. Exercise and/or niacin and/or resverastrol will promote sirtuin expression which restores DNA, including telomeres, and this promotes repairs. It makes more sense that the sirtuins activity that reverses aging gene expression and supported by resverasterol will rejuvenate cells and prevent diseases.
In the right dose these measures(exercise,fasting and the consumption of polyphenols and niacin that affect sirtuin function, are anti-stress and rejuvenating. In higher doses, the stress overshadows protective responses opposing it and becomes counterproductive. So moderate or a little bit of any stress and the right nutrition(mainly raw food) and maintaining low body fat are protective and rejuvenating to the body. Following exercise, NAD levels are lowered by the sirtuins-induced hydrolysis/deacetylation and this further reduces metabolism, free radicals, blood pressure and lifespan is given a further boost.
The benifits of sirtuins and its activators(resverastrol, exercise,fasting and niacin) are seen in eustress with medium level metabolism(producing low level free radicals) with compensatory anti-oxidants generation, histone deacetylation, DNA restoration and restoration of juvenile genes with the renewal of stem cells and de-differentiation that lead to growth, including of telomeres and the increased lifespan.
Dr. Oliver Verbe Birnso, M.D.
Of interest, sirtuins(silent information regulator 2) proteins, protein deacetylators, cause the de-acetylation of acetyl-lysine residues, alongside the hydrolysis of NAD into O-acetyl-ADP-ribose, the deacetylated substrate and nicotinamide, which in an end-product inhibition manner blocks sirtuins activity. Exercise,fasting and niacin which generate NAD(the former two by oxidizing and exhausting stores of NADH, generate free radicals, promote sirtuins activity with increased gene regulation, stem cell renewal and growth. By altering(increasing) the NAD:NADH ratio (a metabolic indicator of free radical production), sirtuins activity is ramped up and deacetylation, including of histones, will promote 'embryonic' or youth pattern of gene expression and support stem cell renewal and even de-differentiation, hence repair and reversal of senescence. Mild oxidative stress is a by-product of and promotes NAD formation, which is a co-target substrate of sirtuins.
Sirtuins therefore are produced in response to mild metabolic(oxidative) stress due to increased NAD, the substrate of the sirtuins deacetylation which, like methylation(with the antioxidant, methionine as substrate) in the reduced environment of the embryo, regulates growth(promotes repair and cell division). Thus altered gene expressions in aging accompanied by high mitochondrial (dys)function, an 'end-point' cellular differentiated state, are re-conditioned and once more become more regulated, as sirtuins go into action, to effect efficient gene expression in repair and rejuvenation. RNA factors(proteins) that bind to and regulate pre-mRNA and determine splicing, will now generate heat shock proteins and other juvenile protein isoforms in the more regulated expression in milder stress. This is, as it were, a replica of what happens during prenatal development, in the mild stress and short-lasting free radical spikes that prompt counter-stress compensations in the restrictive developmental low oxygen womb environment.
Low oxygen tension promotes growth(repair and cell division) and this through gene regulation which further produces a more reduced environment that in turn favors gene regulation but high tension facilates cell differentiation(cellular aging or senescence). There is no better way to achieve gene regulation than through spurts of intensive metabolic activation that produce ATP from NADH and leave behind NAD for sirtuins to act upon in concert with deacetylation. This can be achieved with niacin, exercise and fasting, contrasting with more differentiated tissue that develops where oxygen tension is sustainably high, far away from blood vessels(due to high carbon dioxide acidity). Alternatively, blood vessels(less differentiated) develop farther away from the surface of the skin epithelium (more differentiated), which is in direct contact with the oxygen of air.
Resverastrol(a polyphenol antioxidant found in grapes, peanut, berries and cocoa) is a sirtuin 1 activator. Niacin taken with resverastrol clears most chronic infections due to restored gene expression. Exercise and/or niacin and/or resverastrol will promote sirtuin expression which restores DNA, including telomeres, and this promotes repairs. It makes more sense that the sirtuins activity that reverses aging gene expression and supported by resverasterol will rejuvenate cells and prevent diseases.
In the right dose these measures(exercise,fasting and the consumption of polyphenols and niacin that affect sirtuin function, are anti-stress and rejuvenating. In higher doses, the stress overshadows protective responses opposing it and becomes counterproductive. So moderate or a little bit of any stress and the right nutrition(mainly raw food) and maintaining low body fat are protective and rejuvenating to the body. Following exercise, NAD levels are lowered by the sirtuins-induced hydrolysis/deacetylation and this further reduces metabolism, free radicals, blood pressure and lifespan is given a further boost.
The benifits of sirtuins and its activators(resverastrol, exercise,fasting and niacin) are seen in eustress with medium level metabolism(producing low level free radicals) with compensatory anti-oxidants generation, histone deacetylation, DNA restoration and restoration of juvenile genes with the renewal of stem cells and de-differentiation that lead to growth, including of telomeres and the increased lifespan.
Dr. Oliver Verbe Birnso, M.D.
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