This new paper (see below) seems like good news and further supports the approach of Intranasal Administration of rapamycin…
I contacted the PI / lead author on the paper and he directed me to the paper on his lab’s website where he has a list of all the publications and all of them are free and downloadable. Other interesting papers there are:
- Iron out, mitophagy in!, EMBO Reports , 2020. Download
- A new hypothesis on Alzheimer’s disease: ‘Re-emphasizing early Alzheimer’s disease pathology starting in select entorhinal neurons, with a special focus on mitophagy’, Ageing Research Review 2021. Download
- Autophagy in healthy longevity and disease, Nature Ageing, 2021. Download
- Preclinical and clinical evidence of NAD+ precursors in health, disease, and ageing***, Mechanisms of Ageing and Development*** , 2021. Download.
- Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow, Nature Biomedical Engineering , 2022. Download
- News in UiO, Nature (2022 special issue on ageing), and VG (download the full story).
Compromised clearance of dysfunctional mitochondria, through the process of mitophagy, has garnered attention as an essential contributor to aging and neurodegeneration. Schmid and colleagues1 reveal that genetic enhancement of mitophagy via neuronal overexpression of BNIP3 alleviates brain aging and prolongs healthspan in fruit flies.
In brief, mitophagy is a multistep process that is initiated through the engulfment of damaged or dysfunctional mitochondria by a phagophore, creating a mitophagosome. The mitophagosome fuses with an acidic lysosome, enabling degradation and intracellular recycling of the cargo. BNIP3 is a multifunctional protein that is localized to the outer membrane of the mitochondria, where it can act as either a proapoptotic protein or a mitophagy receptor. BNIP3 participates in the nucleation and elongation steps of mitophagy5 ensuring the recruitment of the phagophore to the mitochondrion by binding to the autophagosome protein, microtubule-associated proteins 1A/1B light chain 3B (Atg8A (known as LC3 in humans))6,7. Furthermore, BNIP3 binds to the central mitophagy protein PTEN-induced kinase 1 (Pink1), blocking its clearance and promoting mitophagy induction8.
Full Paper PDF below: