Urolithins: A Prospective Alternative against Brain Aging

Abstract

The impact of host–microbiome interactions on cognitive health and disease has received increasing attention. Microbial-derived metabolites produced in the gut are one of crucial mechanisms of the gut–brain axis interaction, showing attractive perspectives. Urolithins (Uros) are gut microbial-derived metabolites of ellagitannins and ellagic acid, whose biotransformation varies considerably between individuals and decreases greatly with age. Recently, accumulating evidence has suggested that Uros may have specific advantages in preventing brain aging including favorable blood–brain barrier permeability, selective brain distribution, and increasingly supporting data from preclinical and clinical studies. However, the usability of Uros in diagnosis, prevention, and treatment of neurodegenerative diseases remains elusive. In this review, we aim to present the comprehensive achievements of Uros in age-related brain dysfunctions and neurodegenerative diseases and discuss their prospects and knowledge gaps as functional food, drugs, or biomarkers against brain aging.

Urolithins and Their Precursors Ellagic Acid and Ellagitannins: Natural Sources, Extraction and Methods for Their Determination

“…They are primarily produced by the gut microbiota in humans and some animals that receive ETs and EA through their diet [5]. Specifically, urolithin A (Uro-A) is one of the major metabolites of EA and it has exhibited a wide range of bioactivities, such as anti-inflammatory, antioxidant, anticancer, anti-diabetic and neuroprotective, among others [9,10,[150][151][152].…”

“…Mitophagy efficiency declines with age and in several age-associated pathologies, including myopathies, neurodegenerative diseases and autoimmunities, among others [9]. Notably, mitophagy induction restores the age-dependent mitochondrial damage and rejuvenates cellular fitness by promoting mitochondrial activity and energy metabolism, leading eventually to improved muscle function, neuronal homeostasis, healthspan and lifespan extension [9,10,216,217].…”

“…The consumption of foods rich in ETs and EA has been associated with beneficial effects on human health. As a consequence, a plethora of studies have been performed to shed light on the bioactivities of ETs, EA and Uros [6][7][8][9][10]. Recently, an increasing interest has been focused on the bioactivities of Uros and clinical trials have led Uro supplements to enter into the market [11].…”

Urolithin A affects cellular migration and modulates matrix metalloproteinase expression in colorectal cancer cells

“…Similarly, a separate clinical study revealed that UA led to improvements in muscle strength and aerobic endurance or physical performance in middle‐aged adults over a 4‐month treatment period 18 . Recently, the American Food and Drug Administration (FDA) approved UA for use as a safe ingredient, designating it as Generally Recognized as Safe (GRAS) 19 . As a result, as an alternate or supplementary chemotherapeutic medication, UA may contribute to the treatment of several forms of cancer.…”

“…18 Recently, the American Food and Drug Administration (FDA) approved UA for use as a safe ingredient, designating it as Generally Recognized as Safe (GRAS). 19 As a result, as an alternate or supplementary chemotherapeutic medication, UA may contribute to the treatment of several forms of cancer.…”