Hallmark of Aging 5 - Decreased Autophagy

June 09, 2024

Hallmark of Aging 5 - Disabled MacroAutophagy

Here is another mouthful to learn about. MacroAutophagy, or just autophagy for short. It's how we get rid of the big stuff. In everyday life, your regular garbage goes out in the trash can. If it's too big, you call the company and ask for the big truck to take your ....old freezer, washing machine, or whatever, away.

In your cell, the big garbage truce is called an autophagosome. It is a separate little entity in the cell, designed to surround or envelop old, used-up parts of the cell that need recycling. That autophagosome then fuses with a second entity called a lysosome that is basically a package of digestive enzymes you wouldn't want running loose inside the cell. Whatever is in there, it gets chopped up and all the amino acids, fats, and sugars come out as their basic selves, ready for building something new.

Old mitochondria, broken proteins (often misfolded), bits of misplaced DNA or RNA, and even bacteria and viruses are all chopped up and reprocessed. At least that's how it's meant to work.

Then there is the city dump you can take stuff to. In your cell we call that an exosphere, which is basically a membrane containing the junk to be reprocessed that is packaged up, spit out of the cell into the blood, and destined to be chewed up and digested by white cells called macrophages that envelope it, take it in and digest it. They do it the same way. They have packages of enzymes that fuse with their internal package of "garbage". All neat and tidy.

All these disposal mechanisms give the cell leeway to clean itself up. If one pathway doesn't do it, the next can pick it up. Until it doesn't. There is clear evidence that decreased macroautophagy is a problem. In multiple experimental models, animals with good macroautophagy live longer.

Reduction of autophagic flux may participate in the accumulation of protein aggregates and dysfunctional organelles, reduced elimination of pathogens, and enhanced inflammation because autophagy eliminates proteins involved in the inflammasome and their upstream triggers.

You begin to realize there is a whole universe of research going on into autophagy with several journals dedicated to its discovery. We need it to keep generating fuel when we go through famine, as our bodies selectively break down cellular elements to keep us fed. Mice with knock-out autophagy genes die of hypoglycemia because they can't generate glucose. The list and nuances merit a whole afternoon of reading if you want a rabbit hole to go down.

On the other hand, when garbage accumulates, old, dysfunctional organelles like mitochondria, instigate inflammation. Just like keeping compost in your kitchen starts making a smell and cockroaches move in, the breakdown of autophagy leads to cellular inflammation and eventual early demise.

www.What will Work for me? This gives another reason for some sort of fasting behavior. It sharpens up all your internal tools of autophagy. And one more time, we find an interplay with the Nrf-2 antioxidant controlling system and autophagy. There is a cross-talk and shared enzymes between the two. I can take the supplement PB-125 from Pathways Bioscience because the food extracts in PB-125 stimulate the Nrf-2 system, under which autophagy is at least partially controlled. I pay my village taxes to have my garbage taken each week. I need to restrict calories in some fashion to do the same internally.

References: Cell, Cell, Autophagy, Frontiers Cell Devel. Biol.,

Pop Quiz

1. What is autophagy?                                    Answer: The internal garbage disposal system inside each cell.

2. What is its function?                                Answer: Several key issues. Getting rid of broken intracellular proteins, DNA, and organelles that will induce inflammation is one point. But having the ability to hunker down and reprocess parts of the cell to make fuel in time of lean nutrients is also key.

3. If you knock out an autophagy-controlling gene in mice, what happens if they are deprived of food and go through a spell of starvation?                                 Answer: They die of hypoglycemia.

4. What is the system controlling autophagy?                              Answer: We may not have the whole picture but the Nrf-2 system certainly has overlaps. It is the central controlling system for all inflammation.

5. Is there any one thing I can do to induce better autophagy?                           Answer: Yes, intermittent fasting, forcing your cells to be a bit hungry, induces the internal repurposing function and keeps the enzymes tuned/sharpened. Besides taking PB-125 from Pathways Bioscience.