Therapeutic intervention to mimic the effect of caloric restriction

Abstract

Methods are provided for promoting longevity and decreasing the incidence of aging associated pathologies (e.g., cancer) by the administration of one or more of the following LFFA: linoleic, oleic and palmitic acid. Secondary LFFA derived from this set, as well as their CoA derivatives and synthetic analogs, are effective also in promoting longevity and delaying the onset of age associated disorders. In addition, interventions including LFFA and CoA LLFA formulations are described which protect the organism from acute physical stress, tissue damage and hypoxia (either due to trauma or secondary to surgical procedures.

1 . A method for improving the health of a mammal comprising administering to the mammal a composition comprising LFFA or analogs thereof, or a composition resulting in endogenous release of LFFA, in an amount sufficient to (a) inhibit thyroid hormone receptor binding in vivo, (b) inhibit Na/K ATPase and Ca ATPase in vivo, (c) conserve energy fuels, (d) reduce oxygen consumption in vivo, (e) cause a decrease in core body temperature in said mammal, and/or (f) activation of protective genes in vivo. 
     
     
         2 - 5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein hypoxia tolerance in the mammal is enhanced. 
     
     
         7 - 10 . (canceled) 
     
     
         11 . A method of enhancing tolerance of hypoxia comprising:
 (a) selecting a mammal, and   (b) administering to said mammal a β-adrenergic agonist in an amount sufficient to achieve a systemic level which serves to provide said mammal with a signal equivalent to that experienced during caloric restriction, whereby hypoxia tolerance is enhanced due to reduction in oxygen consumption.   
     
     
         12 . The method of  claim 11 , wherein the β-adrenergic agonist is isoproterenol. 
     
     
         13 . The method of  claim 11 , wherein said hypoxia is acute or chronic. 
     
     
         14 . The method of  claim 11 , wherein said hypoxia is local or systemic. 
     
     
         15 . The method of  claim 11 , wherein said mammal:
 (a) is suffering from a condition selected from the group consisting of angina, cerebrovascular, myocardial, or peripheral vascular insults, pulmonary embolism, and heart failure;   (b) is in situations involving high altitude, undersea, or outerspace operations;   (c) is a surgical candidate; or   (d) is an athlete.   
     
     
         16 . The method of  claim 15 , wherein the mammal is suffering from local or systemic hypoxia due to atherosclerotic artery disease or cerebral ischemia. 
     
     
         17 . The method of  claim 15 , wherein said mammal is a surgical candidate and the administering occurs prior to surgery by an acute course of therapy. 
     
     
         18 . The method of  claim 15 , wherein said mammal is a surgical candidate and the administering occurs during surgery concomitantly with methods for extracorporeal circulation. 
     
     
         19 . The method of  claim 11 , wherein the mammal is a human. 
     
     
         20 . The method of  claim 11 , wherein said β-adrenergic agonist is administered by parenteral, subcutaneous, intramuscular, intravenous, intraperitoneal, intrapleural, intravesicular, intrathecal, oral, rectal, or nasal route. 
     
     
         21 . A method improving the health of a mammal comprising:
 (a) selecting a mammal, and   (b) administering to said mammal β-adrenergic agonist in an amount sufficient to achieve a systemic level which serves to provide said mammal with a signal equivalent to that experienced during caloric restriction, and
 wherein said sufficient amount is determined by monitoring the inhibition of thyroid hormone receptor binding in vivo, inhibition of the Na/K ATPase and Ca ATPase in vivo, conservation of energy fuels, reduction in oxygen consumption, a decrease in core body temperature in said mammal, or activation of protective genes in vivo. 
   
     
     
         22 . The method of  claim 21 , wherein the β-adrenergic agonist is isoproterenol. 
     
     
         23 . The method of  claim 21 , wherein said protective genes are p53, SOD, α-2-globulin, or HSP-70. 
     
     
         24 . The method of  claim 21 , wherein the mammal is a human. 
     
     
         25 . The method of  claim 21 , wherein said β-adrenergic agonist is administered by parenteral, subcutaneous, intramuscular, intravenous, intraperitoneal, intrapleural, intravesicular, intrathecal, oral, rectal, or nasal route.