Introduction
Week 1-2 Physics of Life- Basic Principle of Far from equilibrium thermodynamics (Ilya Prigogine). Video Irreversibility, Video Chaos concept
Oscillations
BZ reaction, Benard Instability, glycolytic oscillations, calcium oscillations, NADP/NADPH oscillations, Limit cycles - circadian clock
Week 3-4 Free Radicals, reactive oxygen species (ROS), reactive nitrogen species (RNS) Free Radicals: What are they? Oxygen, ozone, singlet oxygen, superoxide (radical anion), hydrogen peroxide, hydroxyl radical, nitrogen, oxides of nitrogen, nitroxyl anion, peroxynitrite, chlorine and hyperchlorous acid (Handbook of Redox Biochemistry) .
Theories of Aging
1. Free Radicals
The free radical theory of aging
Mitochondrial stress signals revise an old aging theory.
The cell-non-autonomous nature of electron transport chain-mediated longevity.,
When a theory of aging ages badly.
Extension of mouse lifespan by over-expression of catalase.
Redox proteomics and drug development
2. Mitochondria
Mitochondrial dysfunction as a cause of aging.
Premature ageing in mice expressing defective mitochondrial DNA polymerase,
Somatic mtDNA mutations and aging--facts and fancies.
Mitochondrial stress signals revise an old aging theory.
The Cell-Non-Autonomous Nature of Electron Transport Chain-Mediated Longevity
3. DNA damage as the primary cause of aging
A review and appraisal of the DNA damage theory of ageing
DNA damage and base excision repair in mitochondria and their role in aging.
DNA damage, aging, and cancer.
The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target.
A review and appraisal of the DNA damage theory of aging,
4. Entropy
Genetics vs. entropy: Longevity factors suppress the NF-kB-driven entropic aging process
5. Telomere
SIRT1 contributes to telomere maintenance and augments global homologous recombination.
Resveratrol/Sirtuins: Sirt1- Resveratrol Video, Can autophagy promote longevity?, Resveratrol Attenuates Radiation Damage in Caenorhabditis elegans by Preventing Oxidative Stress,AMPK signaling activation by resveratrol modulates amyloid-beta peptide metabolism, Disruption of a Sirt1-Dependent Autophagy Checkpoint in the Prostate Results in Prostatic Intraepithelial Neoplasia Lesion Formation., Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways., Up-regulation of adiponectin by resveratrol: The essential roles of the Akt/FOXO1 and AMPK signaling pathways and DsbA-L, Resveratrol reduces lipid peroxidation and increases sirtuin 1 expression in adult animals programmed by neonatal protein restriction, Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo.
SIRT6-SIRT6 Promotes DNA Repair Under Stress by Activating PARP1Membrane Oxidase enzymes What are their biological impact?
The NADPH oxidase Nox4 restricts the replicative lifespan of human endothelial cells.
Comparisons between resveratrol and cannabinoids
Neuronal Plasticity:
SIRT1 is essential for normal cognitive function and synaptic plasticity.
Synaptic plasticity in the basal ganglia.
NF-κB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration
Lipids
Essential fatty acids
Omega-3s Omega-6s
Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions
N-acylethanolamines (NAE’s)-Lipid Endocannabinoids: Endocannabinoids: Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice, Cannabinoids and appetite: food craving and food pleasure,
Oxidized Lipids: Oxidized LDL and 4-hydroxynonenal modulate tyrosine kinase receptor activity,Resveratrol inhibits the mTOR mitogenic signaling evoked by oxidized LDL in smooth muscle cells, Impact of Polyunsaturated Fatty Acids on Oxidized Low Density Lipoprotein-Induced U937 Cell Apoptosis., Resveratrol reduces lipid peroxidation and increases sirtuin1 expression in adult animals programmed by neonatal protein restriction, HDL counterbalance the proinflammatory effect of oxidized LDL by inhibiting intracellular reactive oxygen species rise, proteasome activation, and subsequent NF-κB activation
in smooth muscle cells
Adiponectin: Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Up-regulation of adiponectin by resveratrol: The essential roles of the Akt/FOXO1 and AMPK signaling pathways and DsbA-L, Sirtuin-1 regulation of mammalian metabolism, Resveratrol Upregulated SIRT1, FOXO1, and Adiponectin and Downregulated PPARgamma1-3 mRNA Expression in Human Visceral Adipocytes.
Nucleic Acids
DNA repair - Base excision repair Levels of dna damage are unaltered in mice overexpressing human catalase in nuclei.
progeria
Proteins
redox sensitive proteins
transcription factors: Oxidants in signal transduction: impact on DNA integrity and gene expression., DNA damage and base excision repair in mitochondria and their role in aging,Mitochondrial DNA repair and association with aging--an update, The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target.
Quenchers
cellular anti oxidants
Catalase Levels of dna damage are unaltered in mice overexpressing human catalase in nuclei. Extension of mouse lifespan by overexpression of catalase.
Glutathione Wiki
Glutathione Peroxidase The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old.
Peptide Endocannabinoids- Hemeoxygenase: Redox regulation in neurodegeneration and longevity: role of the heme oxygenase and HSP70 systems in brain stress tolerance, The Peptide Hemopressin Acts through CB1 Cannabinoid Receptors to Reduce Food Intake in Rats and Mice, Redox regulation in neurodegeneration and longevity: role of the heme oxygenase and HSP70 systems in brain stress tolerance.
Caloric restriction, Autophagy: Can autophagy promote longevity?, Autophagy in C. elegans, FoxO1 is involved in the antineoplastic effect of calorie restriction, Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney.
Mammalian Target of Rifampin (mTOR): The inhibition of MAPK potentiates the anti-angiogenic efficacy of mTOR inhibitors,
AMP Kinase: overview
Autophagy and Aging
IGF
Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways,
Lon Protease: Impairment of Lon-Induced Protection Against the Accumulation of Oxidized Proteins in Senescent Wi-38 Fibroblasts
Inflammation: Inflammation and Cancer: Inflammation: gearing the journey to cancer
Telomeres: Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood.
HIC1, p53,, FOXO, ppar alpha, beta, gamma, body temperature Klotho Tert NF-kappaB, HSP
drbob rmelamed@uccs.edu (719 641 11885