Ingredients for Proteostasis and Senolytics

Proteostasis & Senolytics for Healthspan and Longevity

 

The Proteostasis Curcumin™ - Proteostasis is the ability to maintain fidelity of protein structures in the body and is viewed as most important in longevity. Important mechanisms behind proteostasis include autophagy, Renewing cellular functioning by recycling componen

  • Autophagy - recycling and renewing cellular components. Removal of toxic protein buildup, such as amyloid beta and tau fibrils.
  • Ingredients for Proteostasis:
    • Curcumin - binds and inhibits toxic protein aggregates.
    • Rosmarinic Acid -  Prevents the buildup of typical tau fibrils and abnormal protein aggregates, which re associated with Alzheimers.(2,3)
    • Ursolic Acid. Reduces proteotoxic stress due to abnormal protein aggregation.(4)
    • Fisetin. Anti-amyloidgenic,

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The Senolytic Curcumin™ - Are compounds which remove dysfunctional scenescent cells, which accumulate with age, and increase lifespan.(1)  Scenescent cells are responsible for inflammation, disease and aging. Such cells age the tissue, and create a toxic environment, affecting adjacent cells and tissue.  Cellular scenescence is viewed as a critical factor in aging. Senolytic compounds, include fisetin, quercetin and curcumin. Among these, fisetin has been shown as the most powerful natural senolytic.(2)

In animal studies, senolytics has been shown to increase healthspan and lifespan in older animals. Specific studies using fisetin supported this analysis by increasing mean and maximum lifespan in older lab mice administered fisetin.(2)

Furthermore, aging and cellular senescence impacts cellular membrane transporters (termed ionic homeostasis), and are involved with many age-related degenerative disease. Fisetin administration improves ionic homeostasis of the cellular membranes.(3)

  As expected, they found that the level of phosphorylated tau protein increase with age and chronic restraint stress (CRS) while inverse relationship was noted for the level of chaperones expression (i.e., diminished with age or stress). CRS was also shown to suppress the expression of Pin1, the peptidylprolyl cis/trans isomerase, in aging animals. All these parameters as well as phosphorylated tau protein and insoluble phosphorylated tau protein formation induced by stress/aging were shown to be revered by RA [].

 

REFERENCES:

PROTEOSTASIS

(1) Dong Y, et al. Nutraceutical Interventions for Promoting Healthy Aging in Invertebrate Models. Oxid Med Cell Longev, 2012

(2) Habetmariam, S. Molecular Pharmacology of Rosmarinic and Salvianolic Acids: Potential Seeds for Alzheimer’s and Vascular Dementia Drugs. Int J Mol Sci, 2018

(3) Cornejo A, et al. Rosmarinic acid prevents fibrillization and diminishes vibrational modes associated to β sheet in tau protein linked to Alzheimer's disease.  J Enzyme Inhib Med Chem. 2017 Dec

(4)

(5) Aarabi MH, et al. To estimate effective antiamyloidogenic property of melatonin and fisetin and their actions to destabilize amyloid fibrils. Pak J Pharm Sci. 2017 Sep

SENOLYTICS

(1) Xu M, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018 Aug

(2) Yousefzadeh MJ, et al. Fisetin is a senotherapeutic that extends health and lifespan.  EBioMedicine. 2018 Oct

(3) Singh S, et al. Fisetin, a potential caloric restriction mimetic, modulates ionic homeostasis in senescence induced and naturally aged rats. Arch Physiol Biochem. 2019 Sep

(4)