MODULATION OF ESTROGEN RECEPTOR-RELATED RECEPTOR GAMMA (ERR GAMMA) AND USES THEREFOR

1 . A method of increasing mitochondrial activity, comprising:

administering a therapeutically effective amount of one or more agents that increases ERRγ activity to a mammal needing increased mitochondrial activity; and

not exercising the mammal.

2 . The method of claim 1 , wherein the method further comprises:

selecting a mammal in need of increased mitochondrial activity or a mammal at risk for developing a disorder that can benefit from increased mitochondrial activity.

3 . The method of claim 1 , wherein increased mitochondrial activity is needed in the mammal's muscle, brain or ear.

4 . The method of claim 1 , wherein the mammal has or is at risk for muscle atrophy, muscle wasting, sarcopenia, hearing loss, mitochondrial encephalomyopathy, lactic acidosis, Leber's hereditary optic neuropathy (LHON), or stroke-like episode syndrome (MELAS).

5 . The method of claim 1 , wherein the one or more agents that increases ERRγ activity comprises:

a nucleic acid molecule encoding ERRγ;

one or more ERRγ agonists;

an ERRγ protein; or

combinations thereof.

6 . The method of claim 1 , wherein the ERRγ agonist is:

or combinations thereof.

7 . The method of claim 1 , wherein the one or more agents that increases ERRγ activity is:

8 . The method of claim 1 , wherein the one or more agents that increases ERRγ activity is:

wherein R is H (DY162), p-CH 3 (DY163), 2-Cl, 3-CF 3 (DY165), p-CF 3 (DY168), p-OCH 3 (DY169), 3-NO 2 , 4CF 3 (DY170), 2,3-O 2 CH 3 (DY174), or m-CH 3 (DY159),

wherein X is S and R is 5-CH 3 (DY166), 5-CH 2 CH 3 (DY164), or 5-NO 2 (DY167);

wherein X is O and R is 4,5-CH 3 (DY173) or CH 2 CH 3 (DY175), or wherein X is CH, and R is 2-Cl, 3-CF 3 , p-CF 3 ; p-OCH 3 , 3-NO 2 , 4-CF 3 ; or 2,3-O 2 CH 3 ;

wherein R is H (DY117) or R is Br (DY172),

wherein

m is 0, 1 or 2;

n is 0, 1 or 2;

R 1 and R 7 are independently selected from

1) H;

2) Halo;

3) OH;

4) (C=0) a , O b C 1 -C 4 alkyl, wherein a is 0 or 1 and b is 0 or 1, wherein the alkyl can be substituted by 0, 1 or more substituted groups independently selected from H or C3C6 heterocyclyl;

5) (C=0), O b C 3 -C 6 cycloalkyl, wherein a is 0 or 1 and b is 0 or 1;

R2 is selected from:

1) H;

2) C 1 -C 3 alkyl, wherein the alkyl can be substituted by 0, 1 or more substituted groups independently selected from H or C 3 C 6 heterocyclyl;

3) C 3 -C 6 cycloalkyl;

or combinations thereof.

9 . The method of claim 3 , wherein increased mitochondrial activity is needed in the mammal's skeletal muscle, and the mammal has or is at risk for muscle atrophy, sarcopenia, or muscle wasting.

10 . The method of claim 3 , wherein increased mitochondrial activity is needed in the mammal's cardiac muscle, and the mammal has or is at risk for a heart attack or ischemia in a cardiac muscle.

11 . The method of claim 1 , wherein the mammal cannot exercise or is sedentary.

12 . The method of claim 1 , wherein the mammal is a human.

13 . The method of claim 1 , wherein the administration comprises parenteral, subcutaneous, intraperitoneal, intrapulmonary, or intranasal administration.

14 . A method of increasing mitochondrial activity by at least 25%, comprising:

administering a therapeutically effective amount of one or more agents that increases ERRγ activity to a mammal needing increased mitochondrial activity; and

not exercising the mammal,

wherein the increase of at least 25% as compared is relative to an amount of mitochondrial activity in the absence of administration of the one or more agents that increases ERRγ activity.