Protein Homeostasis is a significant determining factor in the longevity of multi-cellular animals.(1) Quality control mechanisms in place to support protein homeostasis include autophagy - the essential degradation of toxic proteins. As an organism ages, protein homeostasis is gradually lost.(2) Autophagy, by lysosomes, plays an active role in protein homeostasis, by eliminating toxic and damaged proteins such as amyloid. Nrf2 activation increases autophagy activity. Reduced levels of autophagy are tied to Alzheimers Disease. Misfolded amyloid beta and tau proteins are involved in the development of Alzheimers Disease.(11)
Autophagy is not only critical in the deposition of toxic proteins, but is functionally important in the degradation and recycling of defective cellular components. Research now indicates that autophagy is central for maximum longevity.(13)
AUTOPHAGY: FISETIN and CURCUMIN
AGING - LOSS OF PROTEOSTASIS (TOXIC PROTEINS)
(1) Alavez A, et al. Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature. 2011 Apr
(2) Kuang H, et al, Exploring the bi-directional relationship between autophagy and Alzheimer's disease. CNS Neurosci Ther. 2019 Sep
(3) Chen T, et al. Rapamycin and other longevity-promoting compounds enhance the generation of mouse induced pluripotent stem cells. Aging Cell. 2011 Oct
(4) Yang W, et al. Fisetin improves lead-induced neuroinflammation, apoptosis and synaptic dysfunction in mice associated with the AMPK/SIRT1 and autophagy pathway. Food Chem Toxicol .2019 Sep
(5) Ahmad A, et al. Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice. Mol Neurobiol. 2017 Apr
(6) Singh S, et al. Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration. Life Sci. 2018 Jan
(7) Ziontz J, et al. Tau pathology in cognitively normal older adults. Alzheimers Dement (Amst). 2019 Sep
(8) Yousefzadeh MJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018 Oct
(9) Lin C, et al. Rosmarinic acid improved antioxidant properties and healthspan via the IIS and MAPK pathways in Caenorhabditis elegans. Biofactors. 2019 Jun
(10) De Biase D, et al. Amyloid precursor protein, lipofuscin accumulation and expression of autophagy markers in aged bovine brain. BMC VET Res, 2017.
(11) Buchter C, et al. Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16. Int J Mol Sci. 2913 Jun.
(12) Bielak-Zmijewsja A, et al. The Role of Curcumin in the Modulation of Ageing. Int J Mol Sci. 2019 Mar.
(13) Bareja A, et al. Maximizing Longevity and Healthspan: Multiple Approaches All Converging on Autophagy. Front Cell Dev Biol. 2019 Sep