Method of prevention and treatment of aging and age-related disorders including atherosclerosis, peripheral vascular disease, coronary artery disease, osteoporosis, arthritis, type 2 diabetes, dementia, alzheimer's disease and cancer

A method of prevention and treatment of aging and age-related disorders by inhibition or reduction of Interleukin-6 mediated inflammation in a human or other animal subject through regulation of cholesterol metabolism and isoprenoid depletion, or by direct inhibition of the signal transduction pathway utilizing interleukin-6 inhibitor/antibody, interleukin-6 receptor inhibitor/antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor/antibody, tyrosine kinases inhibitors/antibodies, serine/threonine kinases inhibitors/antibodies, mitogen-activated protein (MAP) kinase inhibitors/antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors/antibodies, Nuclear factor κB (NF-κB) inhibitors/antibodies, IκB kinase (IKK) inhibitors/antibodies, activator protein-1 (AP-1) inhibitors/antibodies, STAT transcription factors inhibitors/antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, PPAR alpha, or a functional fragment thereof. Said method comprises administering, to said subject, separately, sequentially or simultaneously, in amounts which have the effect of ameliorating the vascular and age-related disorders, one or several inhibitors or antibodies of the Interleukin-6 (IL-6) signal transduction pathway selected from synthetic or plant derived polyphenolic compounds including phenolic acids, flavonoids, stilbenes, lignans, Anthocyanidins (e.g., cyanidin, pelargonidin);

• Flavanols (e.g., epicatechin, gallocatechin);
• Flavones (e.g., apigenin, luteolin);
• Flavonols (e.g., kaempferol, myricetin, quercetin);
• Flavanones (e.g., hesperidin, naringenin);
• Isoflavones (e.g., genistein, daidzein, biochanin), Proanthocyanidins, catechin, epicatechin, and their gallic acid esters, Prodelphinidins, gallocatechin, epigallocatechin, and their gallic acid esters as the monomeric units, soy protein material and/or isoflavones selected from genistein, daidzein, glycitein, biochanin A, formononetin, and their naturally occurring glycosides, soy beans, chick peas, ground nuts, lentils and various other types of beans and peas, soy-based food products manufactured from whole soybeans such as tofu, soynuts, soy milk, soy cheese, and soy yoghurt, soy-based food products manufactured in part using soybean-derived protein ingredients such as soy flour, ST flour, ISP, and SPC, Cocoa polyphenols extracted from cocoa beans and derivatives thereof including fresh beans, defatted solids, comminuted trash beans, cocoa powder, low-fat cocoa powder, cocoa shells, cocoa waste, Polyphenols found in nuts, nut skin extracts, tea and tea derivatives, (e.g., Camelliasinensis, C. assamica), coffee beans (Coffeaarabica, C. aniphora, C. robusta, C. liberica) and derivatives thereof, polyphenols of vegetables and fruits including pineapple, wax apple, rambutan, lichi, guava, and mango, mangiferin and polyphenols derived from fruits, vegetables, cereals, dry legumes, chocolate, and beverages, such as grape juice tea, coffee, or wine.

A method of prevention and treatment of aging and age-related disorders by inhibition or reduction of Interleukin-6 mediated inflammation in a human or other animal subject through regulation of cholesterol metabolism and isoprenoid depletion, or by direct inhibition of the signal transduction pathway utilizing interleukin-6 inhibitor/antibody, interleukin-6 receptor inhibitor/antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor/antibody, tyrosine kinases inhibitors/antibodies, serine/threonine kinases inhibitors/antibodies, mitogen-activated protein (MAP) kinase inhibitors/antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors/antibodies, Nuclear factor κB (NF-κB) inhibitors/antibodies, IκB kinase (IKK) inhibitors/antibodies, activator protein-1 (AP-1) inhibitors/antibodies, STAT transcription factors inhibitors/antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, PPAR gamma and/or PPAR beta/delta activators/ligands or a functional fragment thereof. in a human or other animal subject. Said method comprises administering, to said subject, in amounts which have the effect of ameliorating the aging and age-related disorders, a HMG-CoA reductase inhibitor selected from the group including of lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rivastatin, red yeast rice, red yeast grain, red yeast powder and other statins or a pharmaceutically acceptable salt thereof.

A method of prevention and treatment of aging and age-related disorders by inhibition or reduction of Interleukin-6 mediated inflammation in a human or other animal subject. Inhibition of Interleukin 6 mediated inflammation may be achieved indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion or by direct inhibition of the signal transduction pathway utilizing interleukin-6 inhibitor/antibody, interleukin-6 receptor inhibitor/antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor/antibody, tyrosine kinases inhibitors/antibodies, serine/threonine kinases inhibitors/antibodies, mitogen-activated protein (MAP) kinase inhibitors/antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors/antibodies, Nuclear factor κB (NF-κB) inhibitors/antibodies, IκB kinase (IKK) inhibitors/antibodies, activator protein-1 (AP-1) inhibitors/antibodies, STAT transcription factors inhibitors/antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, PPAR alpha, or a functional fragment thereof. Said method comprises administering simultaneously, sequentially or separately, to said subject, in amounts which have the effect of ameliorating the aging and age-related disorders, a bisphosphonate selected from the group including of Pamidronate, Etidronate, Clodronate, Alendronate, phosphonic acid derivatives, an ester thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof.

A method of prevention and treatment of aging and age-related disorders by inhibition or reduction of Interleukin-6 mediated inflammation in a human or other animal subject. Inhibition of Interleukin 6 mediated inflammation may be achieved indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion or by direct inhibition of the signal transduction pathway utilizing interleukin-6 inhibitor/antibody, interleulin-6 receptor inhibitor/antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor/antibody, tyrosine kinases inhibitors/antibodies, serine/threonine kinases inhibitors/antibodies, mitogen-activated protein (MAP) kinase inhibitors/antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors/antibodies, Nuclear factor κB (NF-κB) inhibitors/antibodies, IκB kinase (IKK) inhibitors/antibodies, activator protein-1 (AP-1) inhibitors/antibodies, STAT transcription factors inhibitors/antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, PPAR gamma and/or PPAR beta/delta activators/ligands or a functional fragment thereof. Said method comprises administering, to said subject, simultaneously, sequentially or separately, in amounts which have the effect of ameliorating the vascular and age-related disorders, a cholesterol lowering agent or technique selected from the group including of (i) low cholesterol or low fat diet (ii) sequestrants (cholestyramine, colestipol and dialkylaminoalkyl derivatives of a cross-linked dextran), (iii) nicotinyl alcohol, nicotinic acid or a salt thereof, (iv) PPAR.alpha agonists such as fenofibric acid derivatives (gemfibrozil, clofibrate, fenofibrate and benzafibrate), (v) inhibitors of cholesterol absorption for example beta-sitosterol and ACAT (acyl CoA:cholesterol acyltransferase) inhibitors for example melinamide and (vi) probucol, an ester thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof.