The hypothalamus is a small structure in the brain which is involved in important physiological functions including homeostasis and systemic energy balance, which support health and longevity. Recent research indicates that the neural stem cells found within hyopathalamus may be key to slowing the aging process. However, this not through neurogenesis, but by the secretion of exosomes and microRNA content. (1) Exosomes are vesicles released by the stem cells into the cerebrospinal fluid. Exosomes are an important mechanism for cell-to-cell communications. communication. The content of exsomes include microRNAs, which modifies the expression of genes in the recipient cell.
Inflammation and the Hypothalamus
Longevity of Hypothalamus Neural Stem Cells (Hnsc). With aging there is a significant increase in inflammation, which negatively affects the pool of neural stem cells in the hypothalamus, decreasing their numbers, thereby reducing release of exosomes and microRNA. Most importantly, microRNAs slows aging by inhibiting inflammatory gene expression, thereby improving health of the hypothalamus (3). In experimental animals, the start of aging in the animals began with the loss of hypothalamus stem cells.(4)
Next Article: Supplements supporting health of Hypothalamus and longevity
REFERENCES:
(1) Mendelsohn AR, et al. Inflammation, Stem Cells, and the Aging Hypothalamus. Rejuvenation Res. 2017 Aug
(2) Santos CL, et al, Age-Dependent Neurochemical Remodeling of Hypothalamic Astrocytes. Mol Neurobiol, 2017 Oct 4
(3) Meyer K, et al. Slowing Down Aging. Cell Metabb. 2017 Oct 3
(4) Zhang Y, et al, Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature. 2017 Aug 3
It is known that the activation of FOXO transcription factors promote extreme longevity, which has been demonstrated in research animals as well as in animals such as the multi-cell animal hydra. In human longevity, those with gene variants which activate higher levels of FOXO are also the longest lived with least amounts of illness and disease.
Despite years of research declaring that antioxidants, such as vitamins C and E, promoted longevity, none have been shown to activate the longevity factors FOXO or Nrf2. Rather, potent longevity factor activation has been shown by many plant based flavonoids. (1) Flavonoids are yellow in nature, and the word is derived from the latin flavus, which means yellow.
Other FOXO Activators and Longevity Pathways:
REFERENCES:
(1) Pallauf K, et al. Flavonoids as Putative Inducers of the Transcription Factors Nrf2, FoxO, and PPARγ. Oxid Med Cell Longev. 2017
(2) Paredes-Gonzales X, et al. Induction of NRF2-mediated gene expression by dietary phytochemical flavones apigenin and luteolin. Biopharm Drug Dispos. 2015 Oct
(3) Zhang L, et al. Significant longevity-extending effects of EGCG on Caenorhabditis elegans under stress Free Radic Biol Med.
(4) Wai-Jiao Cai, et al. Icariin and its Derivative Icariside II Extend Healthspan via Insulin/IGF-1 Pathway in C. elegans. PLoS One, 2011
(5) Zhang SQ, et al. Icariin, a natural flavonol glycoside, extends healthspan in mice. Exp Gerontol. 2015 Sep;
(6) Jung HY, et al. Myricetin improves endurance capacity and mitochondrial density by activating SIRT1 and PGC-1α. Sci Rep. 2017 Jul 24
(7) Tang BL. Sirt1 and the Mitochondria. Mol Cells. 2016 Feb
(8) Xiang L, et al. Tetrahydrocurcumin extends life span and inhibits the oxidative stress response by regulating the FOXO forkhead transcription factor. Aging (Albany NY) 2011 Nov
(9) Shen LR, et al. Curcumin-supplemented diets increase superoxide dismutase activity and mean lifespan in Drosophila. Age (Dordr) 2013 Aug;
It has been well studied that the carotenoids lutein and zeaxanthin play an important role in preserving eye function by directly acting as antioxidants. However, new research indicates that these powerhouses go one important step further. This is through the activation the Nfr2 antioxidant defense network.
Nrf2 is a latent protein in the cell, that when activated, becomes a powerful transcription factor that turn on the Antioxidant Response Element (ARE). ARE is the master antioxidant switch in the cell and provides overwhelming antioxidant response, including increased levels of the potent cellular protector glutathione.
LUTEIN ZEAXANTHIN and MESO ZEAXANTHIN act as both direct antioxidants and as Nrf2 activators. Significantly, this makes their protection capacity for the retina significantly greater than only acting as an antioxidant. Implications of this include more capacity to slow the aging of the eye and preserve vision with aging.
NRF2 CELLULAR PROTECTION:
VISION VITALITY MAX (LUTEIN | ZEAXANTHIN | MESO ZEAXANTHIN)
REFERENCES:
(1) Frede K, et al. Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment Epithelial Cells. J Agric Food Chem. 2017 Jun 30
(2) Liu H, et al. Protective effect of lutein on ARPE-19 cells upon H2O2-induced G2/M arrest. Mol Med Rep. 2017 Jun 21.
(3) Lima VC, et al. Macular pigment in retinal health and disease. Int J Retina Vitreous. 2016 Aug
(4) Orhan C, et al. Mesozeaxanthin Protects Retina from Oxidative Stress in a Rat Model. Ocul Pharmocol Ther, 2016 Nov
(5) Firdous AP. et al. Anti-inflammatory potential of carotenoid meso-zeaxanthin and its mode of action. Pharm Biol. 2015 Jul;53(7):961-7.
(6) Zou X, et al. Zeaxanthin induces Nrf2-mediated phase II enzymes in protection of cell death. Cell Death Dis, 2014 May
While we live in an age where people are living longer, an important limiting factor on longevity is the ability of the heart to maintain function. Known causes of death for the oldest people on record (over 110 years old) were recorded as heart failure. Heart failure is due to the gradual loss of cardiomyocytes (heart muscle cells) and the increase in scarring of the heart muscle. The process may take place due to low grade inflammation of the muscle, which progresses with age, or injury (such as a heart attack) which may cause a more sudden loss of heart function. Inflammation in the cardiovascular system is common with the aging process, being the result of hypertension, high blood glucose, trigylcerides, or oxidized VDL cholesterol.
Cardiac Aging Characteristics:
Key Conditions of the Aging Heart
Natural support for Cardio Anti-aging
CARDIO VITALITY (Terminalia Arjuna (Rejuna))
YELLOW LONGEVITY (Curcumin, EGCG, Apigenin, Luteolin, Icariin, Carnosic Acid)*
YELLOW NATURALLY (Curcumin, EGCG, Apigenin, Luteolin, Icariin, Carnosic Acid)*
VISION VITALITY MAX (Lutein, Meso Zeaxanthin)
XGEVITY (Glucoraphanin precursor to Sulforaphane)*
*Andrographolide is also included
REFERENCES:
(1) Steenman M, et al. Cardiac aging and heart disease in humans. Biophys Rev. 2017 Apr;
(2) Zhu ZY, et al. Apigenin ameliorates hypertension-induced cardiac hypertrophy and down-regulates cardiac hypoxia inducible factor-lα in rats. Food Funct. 2016 Apr;7
(3) Liu HJ, et al. Apigenin alleviates STZ-induced diabetic cardiomyopathy. Mol Cell Biochem. 2017 Apr
(4) Hu W, et al. Luteolin improves cardiac dysfunction in heart failure rats by regulating sarcoplasmic reticulum Ca2+-ATPase 2a. Sci Rep. 2017 Jan
(5) Oberoi L, et al. The aqueous extract, not organic extracts, of Terminalia arjuna bark exerts cardiotonic effect on adult ventricular myocytes. Phytomedicine. 2011 Feb 15
(6) Parveen A, et al. Terminalia arjuna enhances baroreflex sensitivity and myocardial function in isoproterenol-induced chronic heart failure rats. J Cardiovasc Pharmacol Ther. 2012 Jun
(7) Kaliq F, et al, Improvement in myocardial function by Terminalia arjuna in streptozotocin-induced diabetic rats: possible mechanisms. J Cardiovasc Pharmacol Ther. 2013 Sept.
(8) Kumar S, et al. Proteomic analysis of the protective effects of aqueous bark extract of Terminalia arjuna (Roxb.) on isoproterenol-induced cardiac hypertrophy in rats. J Ethnopharmacol. 2017 Feb 23
(9) Kocak C, et al, Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats. Life Sci. 2016 Feb 15
(10) Chung RWS, et al. Lutein exerts anti-inflammatory effects in patients with coronary artery disease. Atherosclerosis. 2017 May 6;
(11) Girandola RN, et al. Effect of E-OJ-01 on Cardiac Conditioning in Young Exercising Adults: A Randomized Controlled Trial. Am J Ther. 2017 May
(12) Qian ZQ, et al. Icariin prevents hypertension-induced cardiomyocyte apoptosis through the mitochondrial apoptotic pathway. Biomed Pharmacother. 2017 Apr.
(13) Gu J, et al. Metallothionein Is Downstream of Nrf2 and Partially Mediates Sulforaphane Prevention of Diabetic Cardiomyopathy. Diabetes. 2017 Feb;
(14) Lin CM, et al. Suppressive effect of epigallocatechin-3-O-gallate on endoglin molecular regulation in myocardial fibrosis in vitro and in vivo. J Cell Mol Med. 2016 Nov;
(15) Tan WS, et al. Is there a future for andrographolide to be an anti-inflammatory drug? Deciphering its major mechanisms of action. Biochem Pharmacol. 2017 Apr 2
(16) Lv FH, et al. Effects of curcumin on the apoptosis of cardiomyocytes and the expression of NF-κB, PPAR-γ and Bcl-2 in rats with myocardial infarction injury. Exp Ther Med. 2016 Dec
(17) Khaliq F, et al. Improvement in myocardial function by Terminalia arjuna in streptozotocin-induced diabetic rats: possible mechanisms. J Cardiovasc Pharmacol Ther, 2013 Sep
(18) Hashemzaei M, et al. Regulation of autophagy by some natural products as a potential therapeutic strategy for cardiovascular disorders. Eur J Pharmacol. 2017 May
(19) Hu J, et al. Luteolin alleviates post-infarction cardiac dysfunction by up-regulating autophagy through Mst1 inhibition. J Cell Mol Med, 2016 Jan
(20) Meghwani H, et al. Beneficial effects of aqueous extract of stem bark of Terminalia arjuna (Roxb.), An ayurvedic drug in experimental pulmonary hypertension. J Ethnopharmocol. 2017 Feb 2
(21) Woo AY, et al. Andrographolide up-regulates cellular-reduced glutathione level and protects cardiomyocytes against hypoxia/reoxygenation injury. J Pharmacol Exp Ther. 2008 Apr
(22) Zhang J, et al. Andrographolide Attenuates LPS-Induced Cardiac Malfunctions Through Inhibition of IκB Phosphorylation and Apoptosis in Mice. Cell Physiol Biochem. 2015
(23) Fernandes RO, et al. Sulforaphane effects on postinfarction cardiac remodeling in rats: modulation of redox-sensitive prosurvival and proapoptotic proteins. J Nutr Biochem. 2016 Aug
Protective macular pigments consist of lutein, zeaxanthin and meso zeaxanthin which act as powerful lipid antioxidants as well as functioning as an anti-inflammatory in the retina. In both the retina and the brain, these pigments are readily absorbed into the cellular membranes and orient themselves perpendicular in the membrane which acts to stabilize the cellular membrane.(1) The cellular membrane is made from unsaturated fats, which are very susceptible to free radical induced oxidative damage by high energy short wave light (such as blue light). As a potent lipid antioxidants, lutein, zeaxanthin and meso zeaxanthin signifcantly boost protection of the cellular membrane, and thereby protecting cells of the retina cells and neurons in the brain.(2)
VISION VITALITY MAX (Lutein | Zeaxanthin | Mesozeaxanthin)
REFERENCES:
(1) Subczynski WK, et al. Location of macular xanthophylls in the most vulnerable regions of photoreceptor outer-segment membranes. Arch Biochem Biophys. 2010 Dec
(2) Widomska J, et al. Can Xanthophyll-Membrane Interactions Explain Their Selective Presence in the Retina and Brain? Foods. 2016 Mar.
(3) Neelam K, et al. Putative protective role of lutein and zeaxanthin in diabetic retinopathy. Br J Opthalmol. 2017 May
(4) Gong X, et al. Role of macular xanthophylls in prevention of common neovascular retinopathies: retinopathy of prematurity and diabetic retinopathy. Arch Biochem Biophys. 2015 Apr.
(5) Orhan C, et al. Mesozeaxanthin Protects Retina from Oxidative Stress in a Rat Model. J Ocul Pharmacol Ther. 2016 Nov.
(6) Binxing Li, et al. Studies on the Singlet Oxygen Scavenging Mechanism of Human Macular Pigment.Arch Biochem Biophys, 2010 Dec.
(7) Firdous AP, et al. Amelioration of radiation-induced damages in mice by carotenoid meso-zeaxanthin. Int J Radiat Biol. 2013 Mar
New biomarkers have been identified that may help in the early diagnosis and treatment of prostate and urological cancers. Long non-coding RNA (Ribonucleic Acid), a form of RNA not involved in cellular protein encoding, are altered in these cancers.(1,2)
Expression of long non-coding RNA is believed to play a significant role in the initiation and progression of prostate cancer. Sulforaphane has been found to inhibit the expression of non-coding RNA associated with prostate cancer. Researchers conclude that sulforaphane may prevent and suppress prostate cancer by the inhibition of key non-coding forms of RNA. (3)
XGEVITY (contains Glucoraphanin - Sulforaphane precursor)
AIR VITALITY (contains Glucoraphanin - Sulforaphane precursor)
REFERENCES:
(1) Martens-Uzunova ES, et al. Long noncoding RNA in prostate, bladder, and kidney cancer. Eur Urol. 2014 Jun;
(2) Mouraviev B, et al. Clinical prospects of long noncoding RNAs as novel biomarkers and therapeutic targets in prostate cancer. Prostate Cancer Prostatic Dis. 2016 Mar.
(3) Beaver LM, et al. Long noncoding RNAs and sulforaphane: a target for chemoprevention and suppression of prostate cancer. J Nutr Biochem 2017 Apr;
Energy generation from brown adipose tissue (thermogenesis) is important for maintaining longevity, reducing obesity and supporting energy homeostasis. Brown adipose tissue (BAT) is central to physiological energy homeostasis. Enhancing brown adipose tissue reduces obesity, diabetes, insulin resistance and non-alcoholic fatty liver..
BAT dissipates energy in the form of heat through increased theromgenesis.(1) Browning of white adipose tissue, which converts characteristics of white adipose tissue to brown adipose tissue, increases expression of the thermogenic mitochondrial protein UCP-1. The uncoupling protein 1 (UCP-1) is a potent protein which shifts energy from ATP to heat.
Greater amounts of brown adipose tissue and the thermogenic capacity of the tissue are indicative of youth. With age, brown adipose tissue is decreased, while white adipose tissue becomes predominant and accelerates aging via inflammation and insulin resistance. .
GLUCORAPHANIN - Is a precursor of sulforaphane.
In laboratory mice fed a high fat diet, glucoraphanin supplementation promoted increased energy expenditures via an increase in UCP-1 protein expression in adipose deposit areas. Furthermore, results included decreases in weight, increased insulin sensitivity and improved glucose tolerance.(2)
PTEROSTILBENE - Studied in obese rats, pterostilbene increased the thermogenic capability of the BAT through an upregulation of Ucp1 protein expression..(3)
PURPLE LONGEVITY (Pterostilbene)
(1) Galmozzi A, et al. ThermoMouse: an in vivo model to identify modulators of UCP1 expression in brown adipose tissue. Cell Rep. 2014. Dec.
(2) Nagata N, et al. Glucoraphanin Ameliorates Obesity and Insulin Resistance Through Adipose Tissue Browning and Reduction of Metabolic Endotoxemia in Mice. Diabetes. 2017 Feb 16.
(3) Aguirre L, et al. Effects of pterostilbene in brown adipose tissue from obese rats. J Physiol Biochem. 2017 Feb 27