Mitopure's only reported mechanism of action is mitophagy, induced via the active indgredient Urolithin A.
I still can't help but wonder if other substances that induce mitophagy might be just as beneficial to one's health as Urolithin A. The people at Timeline Nutrition say it works through "a novel mechanism"to induce mitophagy. But seriously, is this novel mechanism more effective then the mechanisms of berberine, resveratrol, spermidine and others -they all induce mitophagy . If in-depth, well financed studies were to be conducted, might these other substances prove to be just as beneficial to a person's health as UA?
I'm not bashing Mitopure, it's a good product. I use it and I would recommend it. It is costly, and that's why the thought still kicks around in my head about these other less expensive mitophagic substances (w the exception of spermidine):
https://www.mdpi.com...21/9/10/932/htm
4.1.1. Curcumin
As seen in
Table 1, curcumin is supposed to exert protective functions via the induction of mitophagy. In detail, its effect on mitophagy might be due to its ability to inhibit the Akt/mTOR pathway, to enhance FOXO1, and to directly induce the PINK1–PARKIN pathway (
Figure 4). Curcumin was also found to elevate mitochondrial biogenesis and genes related to mitochondrial biogenesis, such as SIRT1 and PGC-1α. Regarding
Table 1, curcumin was able to induce mitophagy in the brain in U87-MG and U373-MG malignant glioma cells [
104]. Wang and colleagues also suggest that curcumin is capable of exerting health benefits by improving mitophagy and restoring the mitochondrial function of neurons in rats after brain ischemia–reperfusion [
145]. Furthermore, Liao and colleagues examined the effects of curcumin on aging in
Caenorhabditis elegans (
C. elegans) and showed that curcumin was able to prolong lifespan and decrease the level of ROS [
18]. Moreover, dietary curcumin is able to reduce oxidative stress, improve redox status, and, therefore, lessens mitochondrial damage [
108]. However, its therapeutic oral use for humans is still under debate due to its relatively low bioavailability. Currently, several strategies are being explored, with the aim to improve the absorption and solubility of curcumin, such as inhibiting the curcumin metabolism with adjuvants or novel liquid and solid oral delivery systems [
146].
4.1.2. Astaxanthin
Astaxanthin was shown to induce mitophagy through the activation of PINK1 and PARKIN and the inhibition of AKT/mTOR (
Table 1). Moreover, astaxanthin was able to enhance mitogenesis via the generation of PGC-1α and TFAM (
Figure 4). Yazaki and group reported that astaxanthin has not only strong antioxidant capacities but was also able to increase the lifespan of
C. elegans [
147]. The review of Kidd and colleagues highlights the effects of astaxanthin in aging and age-related disorders and further reports that astaxanthin was able to improve cognition in AD [
148]. Unfortunately, studies investigating the underlying effects of astaxanthin on mitophagy in the brain are still missing.
4.1.3. Resveratrol
As seen in
Figure 4, resveratrol regulates cellular signaling pathways that induce mitophagy (e.g., FOXO3a, PINK1, PARKIN, FUNDC1, BNIP3, AKT/mTOR, and Drp1) and mitochondrial biogenesis (e.g., SIRT1, PGC-1α, and TFAM). The treatment with resveratrol is reported to maintain cellular homeostasis and improve antioxidant capacity [
24]. Resveratrol is capable of upregulating mitophagy in the brain, as indicated in several in vivo studies. Wang and coworkers showed that resveratrol lessened the pathological damage in the frontal cortex and hippocampus in a rat model of chronic cerebral hypofusion via stimulating mitophagy [
125]. Guo and group, as well as Chen and colleagues, mentioned the protective effects of resveratrol through activating mitophagy in the brains of rats [
126,
127]. Resveratrol was also found to promote mitophagy in neuronal cell cultures [
130]. Similar to the other bioactive food compounds, resveratrol may promote organismal healthspan through autophagy enhancement [
149]. Valenzano and coworkers’ findings are in line with this hypothesis, as food supplementation with resveratrol extended the lifespan and retarded the expression of age-related traits in the fish model
Nothobranchius furzeri [
150]. Further, resveratrol was found to counteract the age-related decrease in mitophagy in aging zebrafish (
Danio rerio) [
132].
4.1.4. Olive Oil
Both Oleuropein and hydroxytyrosol are capable of enhancing mitophagy through the upregulation of mitophagy markers such as LC3-II, Beclin, SIRT1, and ULK1, among others, and the downregulation of S6K1 and AKT/mTOR (see
Table 1,
Figure 4). De Pablos and colleagues and Cetrullo and coworkers reported that the increase in mitophagy by hydroxytyrosol, a derivate of oleuropein, was furthermore linked to a decrease in oxidative stress, mitochondrial dysfunction, and cell death [
11,
30]. Notably, extra virgin olive oil administration to a triple-transgenic mice model of Alzheimer’s disease moreover ameliorated memory function, which was associated with autophagy activation [
115]. Rigacci and coworkers highlighted the beneficial effects of oleuropein treatment regarding the stimulation of mitophagy in the brain in neuroblastoma cells and in a transgenic AD mice model [
112]. Moreover, mice brain showed an increase in mitophagy markers after oleuropein feeding, which was confirmed in neuroblastoma cells [
113].
4.1.5. Spermidine
As seen in
Table 1, spermidine induces mitophagy in animal and cell models through the upregulation of mitophagy-related markers such as Beclin-1, LC3-II, PINK1, PARKIN, ULK1, Atg, and AMPK and through the inhibition of mTOR. Spermidine was able to induce mitophagy in mouse neuroblastoma cells [
40], as well as in the brain of aging mice models [
141]. Several studies reported that spermidine consumption not only suppresses aging in yeast, flies, worms, human cells, and mice but also prolongs the lifespan of several model organisms and lessens oxidative stress in aging mice due to autophagy [
151]. Sharma and group also support this hypothesis by stating that spermidine counteracts age-associated cell death by activating autophagy-related mechanisms and reducing the formation of reactive oxygen species [
152].
