Assessing the Affects of Short Term Fasting on the Immune System

One of the interesting findings from research into fasting mimicking diets was that parts of the immune system contract, cell counts diminishing, after about three days. Those cell counts return to normal after the fasting ends. This winnowing and replacement seems beneficial, shedding damaged and problematic cells. In this paper, researchers look at other aspects of the immune system, finding differing beneficial outcomes after a three day fast.

Previous studies have shown that long-term light or moderate fasting such as intermittent fasting can improve health and prolong lifespan. However, in humans short-term intensive fasting, a complete water-only fasting has little been studied. Here, we used multi-omics tools to evaluate the impact of short-term intensive fasting on immune function by comparison of the CD45+ leukocytes from the fasting subjects before and after 72 hour fasting. Transcriptomic and proteomic profiling of CD45+ leukocytes revealed extensive expression changes, marked by higher gene upregulation than downregulation after fasting. Functional enrichment of differentially expressed genes and proteins exposed several pathways critical to metabolic and immune cell functions.

Specifically, short-term intensive fasting enhanced autophagy levels through upregulation of key members involved in the upstream signals and within the autophagy machinery, whereas apoptosis was reduced by down-turning of apoptotic gene expression, thereby increasing the leukocyte viability. When focusing on specific leukocyte populations, peripheral neutrophils are noticeably increased by short-term intensive fasting. Finally, proteomic analysis of leukocytes showed that short-term intensive fasting not only increased neutrophil degranulation, but also increased cytokine secretion. Our results suggest that short-term intensive fasting boost immune function, in particular innate immune function, at least in part by remodeling leukocytes expression profile.



Interesting. Finally some results in humans.
Too bad most of the participants were < 60 yo ( the oldest 69).
I wish they would have measured their proxies for autophagic flux every 24h not only at 0h and 72h.

Currently I'm trying to figure out if using mTOR independent autophagy inducers and/or AMPK activators (e.g. glucosamine, excercise, nicotine) could have the same effects as prolonged fasting. Ideas?

Posted by: Jones at November 10th, 2021 10:57 AM

prolonged fasting probably will lead to the strongest result. It is plausible that it could be enhanced with some supplements to improve the autophagy, cleanup and such. However, not by a large margin. But even a modest improvement can make the fasting shorter or easier to follow

Posted by: Cuberat at November 10th, 2021 1:51 PM

I would like to see some work quantifying if & how much fasting increases susceptibility to infection and potentially risk of severe complications as a result as a result of infection occuring during the fast (or just prior to it but without having yet become symptomatic). Intuitively, dramatic drop in immune cell counts is probably not a good thing for infection during the period in which they are lowered.

Posted by: Karl Pfleger at November 13th, 2021 1:41 PM

seems under-researched: fasting and triggering anemic condition ( always reversible ? )

Posted by: Art Finch at November 13th, 2021 11:55 PM

@Karl Pfleger

Autophagy during viral infection - a double-edged sword

'Viral manipulation of autophagosomes for replication
RNA viruses exploit autophagy for their replication. Double-membrane compartments formed during autophagy can provide a physical platform for the viral replication machinery, locally concentrate essential intermediates and protect viral RNAs from detection by innate immune sensors and degradation.'

Named in the paper:
Coronaviruses (CoVs)
mouse hepatitis virus (MHV)
parainfluenza virus type 3

Posted by: Jones at November 15th, 2021 1:22 AM
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