Uric acid enhances longevity and endurance and protects the brain against ischemia.
Neurobiol Aging
; 75: 159-168, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30576885
ABSTRACT
Among mammals, there is a positive correlation between serum uric acid (UA) levels and life span. Humans have high levels of UA because they lack a functional urate oxidase (UOX) enzyme that is present in shorter lived mammals. Here, we show that male and female mice with UOX haploinsufficiency exhibit an age-related elevation of UA levels, and that the life span of female but not male UOX+/- mice is significantly increased compared to wild-type mice. Serum UA levels are elevated in response to treadmill exercise in UOX+/- mice, but not wild-type mice, and the endurance of the UOX+/- mice is significantly greater than wild-type mice. UOX+/- mice exhibit elevated levels of brain-derived neurotrophic factor, reduced brain damage and improved functional outcome in a model of focal ischemic stroke. Levels of oxidative protein nitration and lipid peroxidation are reduced in muscle and brain tissues of UOX+/- mice under conditions of metabolic and oxidative stress (running in the case of muscle and ischemia in the case of the brain), consistent with prior evidence that UA can scavenge peroxynitrite and hydroxyl radical. Our findings reveal roles for UA in life span determination, endurance and adaptive responses to brain injury, and suggest novel approaches for protecting cells against injury and for optimizing physical performance.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ácido Úrico
/
Encéfalo
/
Isquemia Encefálica
/
Accidente Cerebrovascular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Neurobiol Aging
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos