Urolithin A: Unveiling the Powerhouse Behind the Unusual Name

02/28/2025 16:39:36

Urolithin A: A Natural Enhancer for Intestinal Fortification

In 1980, urolithin A (UA) was initially discovered within the metabolic pathway of ellagic acid (EA) ingestion. Since then, its presence has been detected across various species, from fruit flies to humans. As a key member of the urolithin family, UA is the most common derivative of EA. Sharing similar structures and properties with its precursor, UA has been the subject of extensive research. Notably, UA is scarcely found in the respiratory tract. Its synthesis within the body occurs only when an organism consumes substances rich in natural polyphenol ellagitannins (ET) or ellagic acid (EA), such as pomegranates, and with the assistance of specific microbiome - mediated processes.

Once UA enters the bloodstream, it undergoes partial conversion into conjugates, namely UA - formaldehyde and UA - sulfate. In vitro cell experiments have revealed that these conjugates at this stage largely lose their biological activity.

Regrettably, efficiently harnessing natural polyphenols to produce UA is a challenging task. For instance, human clinical studies indicate that only 40% of individuals can endogenously synthesize UA. This proportion may further decline with age due to alterations in the gut microbiota. Hence, some scholars propose that direct UA supplementation could circumvent this issue.

UA: The “Quality Controller” of the Cell’s “Power Factory” and Its Role in Mitophagy Regulation

The question remains: Is UA merely a “rare curiosity,” or does it possess legitimate anti - aging properties, enhancing overall health and countering the signs of aging? UA has demonstrated its capabilities in its interaction with mitochondria, the “powerhouses” of cells.

One of the primary regulatory mechanisms of UA, observed across multiple species including nematodes, mice, and humans, is its promotion of selective autophagy of damaged mitochondria and its restoration of mitochondrial function impaired by aging. When mitochondria are exposed to external stress and damaged, autophagy is triggered in theory. UA functions as an autophagy inducer, primarily participating in and regulating the mitophagy process through two distinct pathways:

No.1 PINK1/Parkin Ubiquitin - Dependent Pathway

In the ubiquitin - dependent mitophagy pathway, the PINK1 protein first identifies damaged mitochondria. Subsequently, it recruits and phosphorylates the ubiquitin - binding protein Parkin. Together, they facilitate the ubiquitination of mitochondrial proteins, amplifying the autophagy signal and guiding the damaged mitochondria towards phagocytes. UA activates the expression of relevant genes, upregulating the levels of PINK1 and Parkin proteins, thereby accelerating the mitochondrial autophagy process.

No.2 Direct Receptor Activation Pathway

Beyond the PINK1/Parkin pathway, mitochondria can also utilize certain receptor proteins, such as BNIP3, to directly initiate the autophagy process. UA plays a crucial role here by upregulating the expression levels of these receptor proteins, ensuring their stable function and facilitating their accumulation on the mitochondrial surface.

UA: A Potent Agent Against Metabolic Disorders and Its Promise in Life Extension

By targeting mitochondrial regulation, UA plays a pivotal role in maintaining the body’s energy balance and controlling the “cellular engine.” Its reputation is well - deserved. A substantial number of studies have confirmed UA’s significant efficacy in alleviating chronic inflammation, improving cardiovascular health, rectifying muscle dysfunction, and combating neurodegenerative diseases. Despite its remarkable potential, UA has yet to receive widespread industry attention, remaining somewhat of a hidden treasure.

In addition to its broad - spectrum health benefits, UA shows great promise in the realm of anti - aging, particularly in terms of lifespan extension. In a study involving nematodes, long - term UA supplementation (from the egg stage until death) activated the AMPK signaling pathway and significantly enhanced mitophagy. As a result, the lifespan of the nematodes was extended by up to 45.4% compared to the control group.

In the limited human clinical trials conducted thus far, while UA’s impact on human lifespan has not been fully evaluated, the existing results are highly encouraging. UA has been shown to effectively regulate mitochondrial and cellular health within the body. For example, when California strawberry powder, rich in UA precursors, was incorporated into the diet of healthy subjects, improvements in body weight and the presence of beneficial intestinal flora associated with longevity were observed. UA’s journey in the field of anti - aging holds great promise and warrants further exploration.