Protein Homeostasis / Longevity

Protein Homeostasis and Aging

The impact of protein homeostasis on aging rates and longevity is quite significant and has been validated through genetic studies.(1) Protein homeostasis becomes dysfunctional in the cell upon the accumulation of aged damaged proteins, and aggregation of insoluble protein fibrils such as amyloids. Intracellular new protein synthesis and cellular function become disrupted, which can lead to cellular senescence. In neurodegenerative diseases, such as Alzheimers, non-soluble amyloid protein fibrils cause the neurons (brain cells) to degrade and die.

Autophagy, the cells inherent mechanism to clear damaged and aged components (including proteins), is one of the factors critical in this process. Another involves compounds which bind to insoluble protein fibril debris, and breakdown the aggregate to facilitate its removal from the cell. In lab studies, exposure of adult animals (C. Elegans) to an amyloid binding yellow dye (Thioflavin T ) profoundly increased the lifespan of the animals. (1)

Curcumin: Amyloid Binding and Extending Lifespan

Besides the dye, the natural compound curcumin, was also shown to bind to amyloid fibrils, and greatly extend the lifespan of C. elegans (curcumin administration increased the lifespan of C. Elegans by 45%). Lifespan was not only increased, but  this extra longevity was ACTIVE LONGEVITY. That is, that activity level of these animals was maintained, even though longevity was significantly increased! (1) Other studies verify the ability of curcumin to disaggregate amyloid oligomers and fibrils.(3)

Validation of curcumin’s amyloid binding ability is illustrated in another study. The second study involved the administration of BCM-95® curcumin to Alzheimer’s patients, where amyloid fibrils are characteristic of the disease. After administration, blood serum amyloid levels of the Alheimer’s test groups showed significant increases. No such increases were seen in the placebo groups. The conclusion reached by the researchers was that this “possibly reflected the ability of curcumin to disaggregrate amyloid beta deposits in the brain, releasing amyloid beta for circulation and disposal”. (4)

References:

(1) Alavex S, et al. Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature 2011 Apr 14;472(7342):226-9.

(2) Markaki M, et al. The role of autophagy in genetic pathways influencing ageing. Biogerontology. 2011 Feb 24.

(3) Yang F, et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005 Feb 18;280(7):5892-901.  

(4) Baum L, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol 2008 Feb;28(1):110-3