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Cardiac Aging - Heart Failure and Limits of Longevity

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:

  • Increased injury and loss of cardiac muscle due to inflammation and injury,
  • Increased fibrosis and scarring of heart muscle
  • Loss of regenerative ability (cardiomyocytes)
  • Loss of cardiomyocyte homeostasis
  • Reduction in contractile strength of myocytes
  • Increased thickening of muscle (cardiac hypertrophy) - commonly caused by hypertension
  • Diabetes accelerates aging of the heart muscle, and is directly causative of cardiomyopathy - a damaging condition of the heart muscle which leads to heart failure.

Key Conditions of the Aging Heart

  • Atrial Fibrillation
  • Heart Failure (1)
  • Heart failure is primarily the result of insufficient ability to regenerate heart tissue by cardiomyoctes and the replacement of muscle with scar tissue.

 

  • Inhibiting Cardiac Fibrosis and Inflammation supports maintenance of Heart Function with aging.
  • Atrial fibrillation. Changes to the heart through aging, alters the ability of the left atrium to properly conduct the critical electrical impulses, which can cause an abnormal heart beat. Atrial fibrillation results from increased fibrosis in the heart muscle and a remodeling of the heart muscle. Nrf2 activation, which is potently activated by sulforaphane and andrographolide, may reduce fibrosis. 
  • Cardiomyocyte Regeneration and Maintenance (Homeostasis) - Mammal adult heart cells display very poor regenerative ability after incurring inflammation or injury. Instead of regenerating, hearts undergo extensive scarring - reducing functional ability. In order to properly regenerate, there must be a proliferation of cardio myocytes. Hypertension can result in increased cellular death of the cardiomyocytes. An extract of epimedium (icariin) may mitigate the loss of heart muscle due to hypertension.(12) Furthermore, as demonstrated in lab animals, curcumin also may prevent loss of cardiac muscle due to myocardial infarction (heart attack).(16)
  • Cardiomyocyte homeostasis ensures that the heart muscle stays healthy and strong. Cardiac aging leads to a gradual loss of homeostasis, which leads to the death of the cardiomyocyte and eventual heart failure. An important mechanism for maintaining homeostasis is regulated autophagy in the cardiomyocyte. Autophagy eliminates defective proteins and recycles components into new structures.
  • Cardiac scarring is the development of fibrosis in response to an attempt to repair damaged tissue (including inflammation and heart attack). Fibrosis can be reduced by nrf2 activation.
  • Cardiac hypertrophy - is the result of scarring which eventually can lead to cardiac failure. Andrographolide and arjuna have been shown in lab research to inhibit hypertrophy.(2)
  • Contractibility of Cardiomyocytes. Healthy cardiomyocytes have strong contraction capability which may be loss with age and is  factor in heart failure. Luteolin can improve contraction and ameliorate myocardium fibrosis which may improve heart failure.
  • Reducing Myocardial Damage. Carnosic Acid may reduce myocardial damage through properties of anti-inflammatory and antioxidant effects on the heart.(9)
  • Chronic Inflammation - Coronary Artery Disease. Coronary artery disease creates conditions of pervasive inflammation which also affect the heart. Lutein is not only important for vision health, but has potent anti-inflammatory effect in coronary artery patients.(4)
  •  Nrf2 for Oxidative Homeostasis - Aging results in lower levels of nrf2. As a master antioxidant factor, nrf2 is essential to maintain homeostasis of a protective oxidative state for the heart. Increased nrf2 may also protective against cardio fibrosis.

 Natural support for Cardio Anti-aging

  • Terminalia Arjuna (bark extract) - Indian medicine has long recognized arjuna as a cardio tonic and now modern research is supporting this. In young fitness participants, an arjuna extract significantly improved cardiovascular strength and efficiency. Arjuna has also shown potential benefit in heart failure in research animals.(5)
  • Terminalia Arujuna - supports heart function in diabetic rats. Myocardium function improved, as hypothesized by the study researchers, as a result of increased in endogenous antioxidant enzymes.(17)
  • Benefits of Terminalia Arjuna:
    • Improved Diabetic heart function
    • Improved exercise capacity via cardiovascular efficiency
    • Strong improvement of left ventricle output in individuals with cardiovascular ailments.
    • Reduction in mass of cardiac hypertrophy
    • May have beneficial effects on pulmonary hypertension - which is a fatal disease characterized by right ventricular hypertrophy and right heart failure.(20)
    • Protection of cardiac muscle from injury
    • Cardio tonic effect - i.e. positively affecting heart function
  •  Apigenin - Provides supports for hypertrophy and diabetic cardiomyopathy.(2.3)
  •  Luteolin - Supports improved heart muscle contraction in lab animal models of heart failure.(4) Furthermore, in research simulated myocardial infarction (heart attack), luteolin increased autophagy of the heart muscle, increasing mitochondrial biogenesis, thereby lessening subsequent cardiac dysfunction.
  •  Icariin (Epimedium) - helps mitigate hypertension induced cellular death of the   cardiomyocytes.(12)
  •  Lutein - Provides powerful anti-inflammatory action in cardiovascular disease, thereby reducing potential for fibrosis. Lutein is further supportive by acting as an nrf2 activator.  
  • Sulforaphane - Inhibits diabetic cardiomyopathy via the effects as a powerful Nrf2 activator.(13) Experimental research has shown that sulforaphane inhibited cardiomyopathy in both type 1 and type 2 diabetes. In experimental models of cardiac infarctions (heart attack), sulforaphane inhibited changes to the heart muscle, in particular the fibrosis that occurs post-injury.(23)
  • EGCG (Green Tea Extract) - Has an inhibitory effect on myocardial fibrosis.(14)
  • Andrographolide - Nrf2 activator, significantly reducing oxidative stress and potent ant-inflammation agent.(15, 22) Also upregulates glutathione levels in cardiomyocytes, which offers powerful protection against oxygen deprived injury (such as a myocardial infarction). (21) 
  • Curcumin - Regulates autophagy of cardiomyocytes, which supports the degradation and recycling of cardiomyocyte components, such as mis-folded proteins. Autophagy is an essential process in supporting cardiomyocyte homeostasis. When autophagy is dysregulated, the muscle cell dies and may lead to atrophy of the heart and eventually heart failure. In addition to curcumin, resveratrol and berberine also regulate autophagy,(18)

       

      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