Autophagy and Intracellular Aggregates - Dr. Ana Maria Cuervo

[@usernamesdb]

She mentions at 15:30 that chaperone mediated autophagy decreases with age. The cause of this turns out to be a malfunction in the translocation of proteins across the lysosomal membrane which in turn is found to be due to a decrease in the number of LAMP-2A receptors on the lysosome. in other words, in aged animals, chaperones do their job by bringing the garbage proteins to the lysosome, and once inside the lysosome the breaking down of these proteins also seems to be ok in older animals. Rather the problem is in the transfer of the garbage proteins to inside the lysosome and this is due to a decrease in the number of lysosomal associated membrane proteins (LAMP-2A) which are receptors on the surface of the lysosome. She goes on to say how this decrease with age is seen in many species and also in cells of individuals of different ages. She also goes on to say how older mice transfected with an extra copy of LAMP-2A were able, upon tetracycline mediated activation of the extrac gene, were able to restore some autophagic functionality to those similar to young individuals. So my question is what is the reason for the decrease in the LAMP-2A receptors with age?

[@ijohnny.]

usernamesdb Thanks much for this "translation". Your end question is exactly the issue--of life. "Aging" is the "explanation' given for just about everything bad in our bio-systems. But what ABOUT aging is the catalyst? My guess, sudden, or a tipping point reached for major hormone lack/imbalance. Yet thee ust be something more--the accumulation of waste, and the subsequent profound (cellular) degradation of structure.

[@SaraFJones]

usernamesdb great explanation, thank you! That is key!

[@SaraFJones]

usernamesdb here Ivan talks about EAA inhibiting autophagy which may be the one of the reasons why the receptors are not allowing translocation. I'm still living into this.kzbin.info/www/bejne/jWSVfISbna2ggas

[@johnbassett5407]

Very informative and inspiring video. Makes me want to learn more. Thank you.

[@stargazerlily8451]

Shes talking about something of high importance, but her super cool accent and voice makes it more cool!! 😎😎

[@moocat11]

very clear and understandable. Thank you Dr. Cuervo.

[@Me-oq3mx]

Very nice and interesting work. Am your fan now. Un abrazo desde Chile

[@rpa180189]

Amazing class! Thanks from Brazil!

[@persistentone3448]

This presentation mentions briefly that an impaired autophagy system is less able to deal with lipids as a fuel source. Can someone explain the reasons why or provide some citation for that?

[@carolinaagurtoflores5641]

Really great class! thank you very much! :)

[@frankebert4474]

Very, Very good lecture. Thanks from Germany

[@ijohnny.]

Wondering what effect proteolytic enzymes have on these pathways.

[@rscloud79]

this woman is a pure genius,, even though most of what she says goes out one year and out the other. i would just think it's biochemical pathways

[@persistentone3448]

Are there any known methods for naturally enhancing the LAMP-2A performance in aged animals, without resorting to genetic manipulations? Are there currently any trials planned to test LAMP-2A enhancement methods in humans?

[@burritosburritos]

She looks like she does intermittent fasting. Does she?

[@amcmr2003]

Awesome! I wonder how much longer those mice lived.. it sounds like it could already win the mouse prize! Anyway, great lecture on my favorite topic: the lysosomal recycling system. :-)

[@mikepict9011]

Quantum is smaller but soooo much simpler. You have layers of positive neutral and negative charges acids , fats , and alkalines... little doors open with these super cool motors and try and maintain a balance .... shit breaks other shit.... ahh that makes sense to me like the Energizer bunny.... this is beyond me

[@mikepict9011]

Thank you for all your hard work . And sharing it with lay people. Its little more then entertainment for me , but I appreciate it