MITOPHAGY AND LONGEVITY
NRF2 - THE ROLE IN MITOPHAGY AND LONGEVITY Nrf2 is a latent protein in the cell, which upon activation, regulates the activation of genes which produce antioxidant proteins for cellular protection, reduction of inflammation and reduction of mitochondrial toxins (via glutathione induction).
(1) Palikaras K, et al. Mitophagy: In sickness and in health. Mol Cell Oncol. 2015 Jun.
(2) Palikaras K, et al. Coupling mitogenesis and mitophagy for longevity. Autophagy. 2015.
(3) LaPierre L, et al. Transcriptional and epigenetic regulation of autophagy in aging. Autophagy. 2015 Jun
(4) Greco T, et al. Sulforaphane Inhibits Mitochondrial Permeability Transition and Oxidative Stress. Free Radic Biol Med, 2012 Dec
(5) Holstrom Kira, et al. The multifaceted role of Nrf2 in mitochondrial function. Curr Opin Toxicol. 2016 Dec
(6) Wang K, et al. Redox homeostasis: the linchpin in stem cell self-renewal and differentiation. Cell Death Dis. 2013 Mar
(7) Russo M, et al. Nrf2 targeting by sulforaphane: a potential therapy for cancer treatment. Crit Rev Food Sci Nutr. 2016 Dec
(8) O'Mealey GB, et al. Sulforaphane is a Nrf2-independent inhibitor of mitochondrial fission. Redox Biol. 2016 Nov
All aging starts at the cellular level including degeneration of the brain. Science has now identified dysfunction of the neuron mitochondria as the early central initiator in brain degeneration. When the neuronal mitochondria become dysfunctional, there is an inadequate supply of energy to the neuron, and subsequently the neuron dies. Early stages of neurodegenerative diseases have mitochondrial dysfunction common in their pathogenesis including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD) and amyotrophic lateral sclerosis (ALS). Indeed, the failure of cellular bioenergetics has been linked to neuron death and dementia.(1,2)
Research suggests that modulation and inhibition of mitochondrial dysfunction may increase neuron survival and provide a basis for extended brain longevity. As a cytoprotective agent, activation of transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2) protects the functioning of the mitochondria and is viewed as a target for possible prevention and treatment of neurodegenerative diseases associated with aging. Sulforaphane (and precursor Glucoraphanin) is one of the most powerful natural nrf2 activators, and may play a role in the intervention of age-related brain degeneration. (2) In addition, the natural extract andrographolide, carnosic acid and carnosol have been identified as a very strong nrf2 activators. (3, 4)
Both Contain the following nrf2 activators:
(1) Grimm A, et al. Mitochondrial dysfunction: the missing link between aging and sporadic Alzheimer's disease. Biogerontology. 2015 Oct 14.
(2) Denzer I, et al. Modulation of mitochondrial dysfunction in neurodegenerative diseases via activation of nuclear factor erythroid-2-related factor 2 by food-derived compounds.
Pharmacol Res. 2015 Nov 25.
(3) Wu KC, et al. Screening of natural compounds as activators of the keap1-nrf2 pathway.
Planta Med. 2014
(4) de Oliveira MR. The Dietary Components Carnosic Acid and Carnosol as Neuroprotective Agents: a Mechanistic View. Mol Neurobiol. 2015 Nov 9