News

Mitophagy - Maintaining Mitochondria & Stem Cell Renewal for Regenerative Longevity

MITOPHAGY AND  LONGEVITY

• Cellular homeostasis, which significantly includes mitochondria function, is critical for longevity. Mitochondria are the energy powerhouses of the cell and are essential cellular elements for health and longevity. As part of aging, the mitochondria accumulate damage which decreases cellular vitality while increasing dysfunction. Mitophagy is the ability to clean the cell of damaged mitochondria which, if left to accumulate, would cause irreversible loss of cellular energy. Dysfunctional mitochondria can lead to cellular death, degenerative diseases and shorten the lifespan.

• Mitophagy is essential for longevity. Higher activity levels of  mitophagy in the cell has been linked to significant increases in longevity in research animals. Improved aging and extended longevity is correlated with a proper balance of mitochondria biogenesis and mitophagy.(1) Age-related decreases in mitophagy result in the accumulation of damaged mitochondria and a decrease in mitochondria biogenesis, 

• Mitophagy and Autophagy. Mitophagy is the selective degradation of the mitochondria by cellular process known as autophagy. Autophagy is the cellular process used to remove damaged cellular organelles and debris. Increased autophagy is known as a critical component in cellular survival and longevity. Enhanced levels of autophagy is considered a major factor in the  increased longevity in long lived animals.(2)

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).

• Nrf2 Increases Mitochondria Biogenesis and Mitophagy. .

• Stem Cells - The basis for extreme longevity. Extreme lifespans are based on the ability to regenerate new cells to replace damaged cells. This is the function of stem cells. Stem cells are undifferentiated cells which, when needed, can differentiate into replacement cells in the body. Examples where stem cells differentiate into new functional cells include cardiomyoctyes (heart cells) and neurons in the brain. Sources of stem cells include a stem cell pool, whereby stem cells undergo a self-renewal (making new stem cell cells) which supply this pool. Additionally there are specific stem cells such as neural stem cells which can produce new neurons in the brain. Aging, and the dysfucntion of stem cell mitochondria, decrease the functional ability of stem cell self renewal and the regeneration ability of stem cells into cells such as neurons.

• Nrf2 Protects Stem Cells Capacity for Self-Renewal and Differentiation, When levels of Nrf2 are decreased, stem cells and progenitor cells, lose their function for the self renewal and regeneration of cells.. An example of this is seen in neural stem cells in the brain where the ability to stimulate new neuron growth from stem cells  is inhibited when nrf2 levels are low. Researchers believe that nrf2 promotes healthy mitochondria in the stem cells which in turn reverses age related decline in stem cell ability to self-renew and to regenerate new cells. Therefore, nrf2 activation is significant in stem cell self renewal as well as cellular regeneration, including cardiomyocyte regeneration and preserving the function of neural stem cells.(5,6)  

• SULFORAPHANE is a natural and potent Nrf2 Activator and helps maintain youthful and healthy mitochondria. (4, 7)
• SULFORAPHANE - BEYOND Nrf2. In addition to providing Nrf2 activation, sulforaphane helps block damage to the mitochondria through non-Nrf2 mechanisms. Sulforaphane supports mitochondria hyperfusion, which is cytoprotective and prevents the formation of pores in the mitochondria.(8)

REFERENCES:

(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 

Brain & Neurodegenerative Diseases - The Central Role of Mitochondria

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)

XGEVITY

AIR VITALITY

Both Contain the following nrf2 activators:

• Glucoraphanin / sulforaphane – from broccoli
• Andrographolide – from andrographis paniculata
• Carnosol & Carnosic Acid – from rosemary extract

REFERENCES:

(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