Hacker News new | past | comments | ask | show | jobs | submit login

A very potent way to induce autophagy seems to be through fasting [0]. As far as I understand measuring autophagy accurately across different cell types in a living organism/human as autophagy flux is still a big challenge and e.g. Peter Attia emphasizes in his podcasts there is no reliable way to effectively measure autophagy, unfortunately he didn't bother to go in depth. The papers I've found about measuring autophagy are painting a more confident picture, though.

[0]https://www.sciencedirect.com/science/article/pii/S156816371...




Thanks! Which papers? And in summary, what do they say?


So this interesting review [0] from 2017 is very cautious; from the last paragraphs of the concluding remarks:

>Detection of autophagy markers such as LC3-II and/or of accumulation of autophagy substrates such as p62 has been attempted using autopsy or biopsy samples from human patients. However, static analyses cannot distinguish between autophagy upregulation and degradation inhibition, and an increased amount of p62 is not necessarily caused by inhibition of autophagy as described above. Furthermore, human samples are often limited in quality due to difficulty in obtaining fresh tissues, thus the data need particularly careful evaluation taking into consideration possible effects caused by sample quality and preparation. Presently, there is no established method to measure autophagic flux in humans; therefore, it remains practically impossible to monitor autophagy properly in humans. Static analyses with the limitations stated above are often misleading, or can provide only suggestive results at best. Genetic mutations in humans that may cause changes in autophagic flux have been studied using patient-derived cells such as fibroblasts, lymphoblastoid cell lines, or induced pluripotent stem cells differentiated into the affected tissues. Autophagic flux can be tested properly in these cells ex vivo. How much the results using cell types differing from affected tissues, or how much the defects observed ex vivo reflect the pathology of patients and the cause of symptoms remain to be addressed.

This newer review [1] is also cautious but a bit more optimistic:

>Should we aspire to have a definitive autophagy assay? It depends. Given that this pathway is part of a larger endocytic and metabolic signaling network, there will always be a need to investigate mechanistic questions using different assays. With that said, the field could benefit from having an endogenous flux readout that works across cell lineages without the need to engineer cells up-front. Imaging and analytical probes delivered exogenously to cells, animals, and patients could be envisioned here. Moreover, detection of circulating autophagy by-products and/or molecular responses to pathway modulation could be investigated as candidate biomarkers (see Outstanding Questions). Taking future innovative steps towards the measurement of autophagy will greatly enable the discovery of fundamental mechanisms and the development of autophagy-based therapies. In the clinic, such biomarkers will provide an early and robust view of therapeutic target modulation, which will drive decisions around adapting dose schedule and intensity, which will bring greater benefit to patients.

And this commentary [2] is quite optimistic:

>The control of autophagy manipulation and the measurement of autophagic flux in vivo remains challenging, yet it is a crucial requirement for the safe and finely controlled application of autophagy manipulation in the clinic. The current techniques to measure autophagy accurately may already exist, but have to be aligned to operate on the one hand in a multi-scale fashion and on the other hand to be suitable for high-throughput high-resolution quantitative analysis in a living tissue and organism. Here we have provided examples for how we may address some of the challenges around measuring autophagic flux in vivo, how to discern steady state and the maintenance of a suitable autophagic activity, how to assess autophagy drugs for their potency and to correlate these data with disease-specific markers of cargo or health. Future application of these aspects using living model systems, for example, viable transgenic murine embryos or candidate tissues that express the required autophagy markers, will be of high value to provide answers and the resolution to further build on the pioneering work that targets autophagy assessment in vivo and in the clinic, thereby assembling a picture of a systemic autophagy status.

[0]https://www.mdpi.com/1422-0067/18/9/1865/htm

[1]https://www.sciencedirect.com/science/article/pii/S096800042...

[2]https://www.tandfonline.com/doi/full/10.1080/15548627.2019.1...


Fantastic. Thanks a lot. Reading your pointers now.




Join us for AI Startup School this June 16-17 in San Francisco!

Guidelines | FAQ | Lists | API | Security | Legal | Apply to YC | Contact

Search: