ENHANCING AUTOPHAGY OR INCREASING LONGEVITY BY ADMINISTRATION OF UROLITHINS
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 skin disorders in a subject in need thereof, comprising administering to the subject an effective amount of a urolithin, wherein the skin disorder is selected from environmental insults and skin injury from excessive lipid oxidation in aged and diseased skin.
115 . The method of claim 114 , wherein the skin disorder is selected from environmental insults.
116 . The method of claim 114 , wherein the skin disorder is skin injury from excessive lipid oxidation in aged and diseased skin.
117 . A method of improving or increasing autophagy in an animal in need thereof, comprising administering to the animal an effective amount of a urolithin, wherein the autophagy is improved or increased in cells of the animal selected from skin cells.
118 . The method of claim 117 , wherein the skin cells comprise keratinocytes.
119 . A method of improving or increasing autophagy in an animal in need thereof, comprising administering to the animal an effective amount of a urolithin, wherein the autophagy is improved or increased in a tissue or organ of the animal selected from skin.
120 . A method of improving or increasing autophagy in an animal in need thereof, comprising administering to the animal an effective amount of a urolithin, wherein the autophagy is improved or increased in cells of the animal selected from epithelial cells and endothelial cells.
121 . A method of treating skin disorders in a subject in need thereof, comprising administering to the subject an effective amount of a urolithin, wherein the urolithin is combined with 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.
122 . A method of treating skin disorders in a subject in need thereof, comprising administering to the subject an effective amount of a urolithin, wherein the urolithin is combined with one or more agents selected from 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).
123 . A method of treating skin disorders in a subject in need thereof, comprising administering to the subject an effective amount of a urolithin, wherein the urolithin is combined with one or more agents selected from resveratrol, pyrroloquinoline quinone, genistein, hydroxyltyrosol, and quercetin.
124 . The method of claim 114 , wherein the urolithin is any one or a combination of urolithin A, urolithin B, urolithin C and urolithin D, for example, urolithin A.
125 . The method of claim 114 , wherein the urolithin or combination thereof is administered topically.
126 . The method of claim 115 , wherein the environmental insult is UV light.
127 . The method of claim 117 , wherein the autophagy is mitophagy.
128 . The method of claim 119 , wherein the autophagy is mitophagy.
129 . The method of claim 120 , wherein the autophagy is mitophagy.
130 . The method of claim 121 , wherein the urolithin is combined with resveratrol or spermidine.
131 . The method of claim 122 , wherein the urolithin is combined with vitamin C.
132 . The method of claim 123 , wherein the urolithin is combined with resveratrol.