Friday, April 17, 2009

Paleo and PPAR For Max Longevity

Mitochondria, DNA and Our Hearts

Nick Lane (author, Power Sex Suicide) also discussed how a small cost exists for the mitochondria to each contain, replicate, and maintain their own set of mtDNA. The costs must be worth the expense and final outcomes for cellular energetics, survival and, ultimately, longevity.

All day everyday 24/7 our bodies are correcting DNA damage, mutations and breakage in mitochondria and in the prime control center, the nucleus. DNA repair requires optimal functioning of crucial enzymes, critical hormone pathways, the presence of co-factors, and the absence of ROS and other oxidative stressors.

We employ ALL of these strategies at TYP for optimum regression of obstructive heart disease as detected, identified and calculated on EBT calcium scoring.

The TYP Program includes:
--Paleo eating (Read Dr.Davis' Cordain interview for TYP: HERE)
--Paleo exercise (eg, functional hypertrophy)
--Lp(a) identification and correction (17-25% of population carries)
--Homocysteine identification and correction
--Small dense LDL particle quantification and correction
--Hormone dysregulation and optimization to youthful levels (Vitamin D, Thyroid, INSULIN, DHEA, Melatonin, Estrogen, Progesterone, Testosterone, Cortisol, etc)
--Antioxidants with anti-inflammatory properties: High dose Omega-3, Niacin Vitamin B3 1-2 g/day, Vitamins ADE K1 K2 MK-7 MK-4, Vitamin C, Phosphatidylcholine, B-vitamins, Minerals Mg Zn Se etc, etc

Everyone who correctly identifies the 'problem' and correctly fixes the 'problem' achieves reductions in calcium scores in 1-3yrs. The side effects reported are: better senses (seeing, smelling, balance, reflexes), vitality, energy, weight loss, lower BP/glucose/resting pulse, improved cholesterol, glowing skin/hair/nails, etc. Besides plaque regression/stabilization and long-term heart protection (statins, optional *WINK*)... Oh BTW ... Maximum longevity, cancer protection, easy weight loss, body fat recomposition...looking H-A-W-T and Paleo-appealing *HA*, obesity-resistance, and being idiot-proof (ok... j/k!) are additionally guaranteed.

...Who doesn't desire a degree of that?

  • Mitochondria in the human heart.
    Lemieux H, Hoppel CL. J Bioenerg Biomembr. 2009 Apr 8.
    Center for Mitochondrial Disease, Department of Pharmacology and Medicine, School of Medicine, Case Western Reserve University
    The heart relies mainly on mitochondrial metabolism to provide the energy needed for pumping blood to oxygenate the organs of the body. The study of mitochondrial function in the human heart faces many obstacles and elucidation of the role of mitochondria in cardiac diseases has relied mainly on studies with animal models. Cardiac diseases are the leading cause of mortality worldwide. With the emergence of new therapies to treat and prevent heart disease, some aiming at metabolic modulation, a need for acquiring a better understanding of mitochondrial function in the human heart becomes apparent. Our review is aimed at specific evaluation of the human heart in terms of
    (1) methods to understand mitochondrial function, with particular emphasis on integrated function,
    (2) data on the role of mitochondrial dysfunction in cardiovascular disease, and
    (3) possible applications of this knowledge in the treatment of patients with cardiac disease.
    PMID: 19353253
  • Mitochondrial dysfunction as an initiating event in atherogenesis: a plausible hypothesis.
    Puddu P, Muscari A et al. Cardiology. 2005;103(3):137-41.
    It is now widely accepted that oxidant stress and the ensuing endothelial dysfunction play a key role in the pathogenesis of atherosclerosis and cardiovascular diseases. The mitochondrial respiratory chain is the major source of reactive oxygen species as byproducts of normal cell respiration. Mitochondria may also be important targets for reactive oxygen species, which may damage mitochondrial lipids, enzymes and DNA with following mitochondrial dysfunction. Free cholesterol, oxidized low-density lipoprotein and glycated high-density lipoprotein are further possible causes of mitochondrial dysfunction and/or apoptosis. Moreover, in patients with mitochondrial diseases, vascular complications are commonly observed at an early age, often in the absence of traditional risk factors for atherosclerosis. We propose that mitochondrial dysfunction, besides endothelial dysfunction, represents an important early step in the chain of events leading to atherosclerotic disease.
  • Mitochondrial integrity and function in atherogenesis.
    Ballinger SW, Runge MS et al.
    Circulation. 2002 Jul 30;106(5):544-9.
  • The role of mitochondria in ischemic heart disease.
    Ferrari R.
    J Cardiovasc Pharmacol. 1996;28 Suppl 1:S1-10. Review.

Pimp Your PPARs! For Obesity Resistance

The family of PPAR nuclear receptors (NRs) are one of the ultimate controllers of inflammation, growth, proliferation, nutrient sensing, metabolism, and most importantly energy homeostasis. Remember, energy IN does not equal energy OUT. G-Flux post.

The medical literature only recently in the last 10-15 yrs exploded with information about these regulators of life. One of the newest elucidated pieces of the puzzle is that PPAR-Delta controls mitochondrial metabolism (uncoupling) in brown fat (our 'good' storage fat...keeps us warm when we shiver and many MANY other good things). The authors from the east coast remark, "Interestingly, the nuclear receptor PPARdelta not only mediates the actions of PGC-1alpha but also regulates twist-1 expression, suggesting a negative-feedback regulatory mechanism... In vivo, transgenic mice expressing twist-1 in the adipose tissue are prone to high-fat-diet-induced obesity, whereas twist-1 heterozygous knockout mice are obesity resistant. These phenotypes are attributed to their altered mitochondrial metabolism in the brown fat. " Pan D et al. Cell. 2009 Apr 3;137(1):73-86.

Significance of peroxisome proliferator-activated receptors in the cardiovascular system in health and disease.
Robinson E, Grieve DJ.
Pharmacol Ther. 2009 Mar 24.

Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation.
Chinetti G, Fruchart JC, Staels B.
Inflamm Res. 2000 Oct;49(10):497-505. Review.

Novel approach to treat insulin resistance, type 2 diabetes, and the metabolic syndrome: simultaneous activation of PPARalpha, PPARgamma, and PPARdelta.
Evans JL, Lin JJ, Goldfine ID.
Curr Diabetes Rev. 2005 Aug;1(3):299-307. Review.

Peroxisome proliferator-activated receptors and the control of inflammation.
Cabrero A, Laguna JC, Vázquez M.
Curr Drug Targets Inflamm Allergy. 2002 Sep;1(3):243-8. Review.

Peroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications.
Touyz RM, Schiffrin EL.
Vascul Pharmacol. 2006 Jul;45(1):19-28. Epub 2006 Jun 16. Review.

Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells.
Marx N, Duez H, Fruchart JC, Staels B.
Circ Res. 2004 May 14;94(9):1168-78. Review.

Peroxisome proliferator-activated receptor family and its relationship to renal complications of the metabolic syndrome.
Guan Y.
J Am Soc Nephrol. 2004 Nov;15(11):2801-15. Review.

Peroxisome proliferators and peroxisome proliferator activated receptors (PPARs) as regulators of lipid metabolism.
Latruffe N, Vamecq J.
Biochimie. 1997 Feb-Mar;79(2-3):81-94. Review.

Peroxisome proliferator-activated receptor alpha (PPARalpha) and athero-sclerosis.
Gouni-Berthold I, Krone W.
Curr Drug Targets Cardiovasc Haematol Disord. 2005 Dec;5(6):513-23. Review.

Pleiotropic actions of PPAR gamma activators thiazolidinediones in cardiovascular diseases.
Takano H, Hasegawa H, Zou Y, Komuro I.
Curr Pharm Des. 2004;10(22):2779-86. Review.

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