Autophagic Flux Does Not Decline with Age in Dermal Fibroblasts

Autophagy is a collection of cellular maintenance processes that recycle damaged or unwanted proteins and structures. It is generally considered to become less effective with age, and that this decline is an important aspect of aging, but nothing is simple in cellular biochemistry. For any well supported topic there are always exceptions and there is always at least some opposing evidence. Here, researchers report on data that shows autophagy to be just as active in old dermal fibroblasts as it is in the younger versions of such cells. It is hard to say what to make of that, given the sizable weight of all of the existing evidence for age-related dysfunction in autophagy, whether taken as a whole, or examining specific subsystems vital to the overall process.

Autophagy is an intracellular stress response that is enhanced under starvation conditions, and also when the cellular components are damaged. Aging accompanies an increase in intracellular stress and has significant impact on the skin. Since dermal fibroblasts are a powerful indicator of skin aging, we compared the autophagic activity of human skin fibroblasts between the young and old. The number of autophagosomes per cytoplasmic area was similar between young and aged fibroblasts. The amount of LC3-II, a form associated with autophagic vacuolar membranes, was also similar between the groups. Although residual bodies were more common in aged dermal fibroblasts, LC3 turnover and p62 assay showed little difference in the rate of lysosomal proteolysis between the young and old. RNA-seq analysis revealed that the major autophagy-modulating genes were not differentially expressed with age.

Our results suggest that the basal autophagic flux in aged dermal fibroblasts is largely comparable to that of young fibroblasts. However, with a higher speed and amount of waste production in aged cells, we postulate that such autophagic flux may not be sufficient in keeping the old cells "clean", resulting in skin aging. Aging is a complex process and, as such, the relationship between autophagy and aging is not straightforward. That is to say, autophagy does not simply decline with age. Regardless of the controversies on autophagic activity with age, autophagy plays a crucial role in counteracting aging, and strategies aimed at its modulation should hold promise for the prevention of skin aging.



It could be also that, even though the lysosomes and autophagy Gene expression doesn't change, the autophagy levels could still be inadequate. Either as suggested by the article as having higher burden , or being less effective for some other reason like missing enzymes or energy. Or the stress response is not vigorous enough... Of course this is one specific tissue. Since the skin has to renew itself more often , the skin fibroblasts might be aging differently, or at slower rate.

Posted by: cuberat at August 9th, 2018 8:47 AM

I did my first Dr. Group 4-day water fast (to encourage autophagy) 2 years ago, and did 2 more, one every 6 months. In June, I started doing them every month.

"However, with a higher speed and amount of waste production in aged cells, we postulate that such autophagic flux may not be sufficient in keeping the old cells "clean", resulting in skin aging"

I'm running faster in response.

Posted by: Tom Schaefer at August 9th, 2018 9:00 AM

Hi Tom,
Are you combining fast with food supplements like NAD or querc├ętine? Are you planning on longer durations? So you see any measurable effects?

Posted by: Cuberat at August 9th, 2018 7:54 PM

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