Enhancing autophagy or increasing longevity by administration of urolithins

Abstract

Disclosed are methods, compounds, and compositions useful for increasing autophagy and promoting longevity. The methods, compounds, and compositions relate to urolithins and urolithin precursors and use thereof. Certain urolithins are represented by Formula I, while certain urolithin precursors are represented by Formula IV. The urolithin may be urolithin A, urolithin B, urolithin C, or urolithin D. The urolithin precursor may be ellagic acid or an ellagitannin. The methods include in vivo, ex vivo, and in vitro uses of the compounds and compositions.

1 - 113 . (canceled) 
     
     
         114 . A method of treating a skin disorder, comprising administering to an animal in need thereof an effective amount of a urolithin. 
     
     
         115 . The method of  claim 114 , wherein the skin disorder is selected from skin aging and skin inflammation. 
     
     
         116 . The method of  claim 114 , wherein the skin disorder is skin aging. 
     
     
         117 . The method of  claim 114 , wherein the skin disorder is selected from intracellular skin infections, warts and psoriasis. 
     
     
         118 . The method of  claim 114 , wherein the skin disorder is selected from environmental insults, for example, UV light. 
     
     
         119 . The method of  claim 118 , wherein the environmental insults are caused by UV light. 
     
     
         120 . The method of  claim 114 , wherein the skin disorder is skin injury from excessive lipid oxidation in aged and diseased skin. 
     
     
         121 . A method of improving or increasing autophagy, comprising administering to an animal in need thereof an effective amount of a urolithin, wherein the autophagy is improved or increased in cells of the animal selected from skin cells, epithelial cells, and endothelial cells. 
     
     
         122 . The method of  claim 121 , wherein the skin cells comprise keratinocytes. 
     
     
         123 . The method of  claim 121 , wherein the autophagy is improved or increased in cells of the animal selected from epithelial cells and endothelial cells. 
     
     
         124 . A method of improving or increasing autophagy, comprising administering to an animal in need thereof an effective amount of a urolithin, wherein the autophagy is improved or increased in a tissue or organ of the animal selected from skin. 
     
     
         125 . The method of  claim 114 , further comprising administering one or more agents selected from rapamycin, metformin, resveratrol, spermidine, epigallocatechin gallate, genistein, silibinin, curcumin, clonidine, rilmenidine, tyramine, morphine, baclofen, mastoparan, propranolol, bupivacaine, N-dodecyl lysinamide, tamoxifen, IFN-gamma, trehalose, and vinblastine. 
     
     
         126 . The method of  claim 114 , further comprising administering one or more agents selected from coenzyme Q10 as ubiquinol, coenzyme Q10 ubiquinone, riboflavin (vitamin B2), L-creatine, L-arginine, L-carnitine, the B vitamin complexes B50 or B100, vitamin E, vitamin C, alpha-lipoic acid, and folinic acid (for example, leucovorin). 
     
     
         127 . The method of  claim 114 , further comprising administering one or more agents selected from resveratrol, pyrroloquinoline quinone, genistein, hydroxyltyrosol, and quercetin 
     
     
         128 . The method of  claim 114 , wherein the urolithin is any one or a combination of urolithin A, urolithin B, urolithin C and urolithin D. 
     
     
         129 . The method of  claim 114 , wherein the urolithin is urolithin A. 
     
     
         130 . The method of  claim 128 , wherein the urolithin or combination thereof is administered topically. 
     
     
         131 . The method of  claim 129 , wherein the urolithin A is administered topically.