Para algunos investigadores del envejecimiento, el secreto de la longevidad es simple: comer menos.
Décadas de investigación han demostrado que la restricción moderada de calorías, sin ninguna otra intervención, aumenta la esperanza de vida saludable en moscas, gusanos y ratones. Sin embargo, mencionar la restricción calórica, o «RC», en humanos en cualquier foro de longevidad, desencadenará un furioso debate entre los defensores acérrimos y los disidentes apasionados.
La razón también es simple: solo tenemos teorías, pero carecemos de datos suficientes en humanos. Es extremadamente difícil realizar una prueba que obligue a las personas a reducir constantemente sus calorías de manera controlada. Después de todo, pocas personas quieren seguir constantemente una dieta estricta. Y si el truco funciona, es aún más difícil averiguar por qué. Pero si podemos echar un vistazo a los fundamentos biológicos de la restricción calórica, podríamos activar artificialmente «programas» moleculares que aumenten la esperanza de vida, mientras desactivamos aquellos que son perjudiciales para una vida larga y saludable.
Entra CALERÍA. El ensayo Evaluación integral de los efectos a largo plazo de la reducción del consumo de energía es el primer estudio controlado de RC en el Joe promedio, dirigido por científicos de la Universidad de Yale y Pennington Biomedical Research, el ensayo encontró que reducir las calorías en solo un 14 por ciento durante 2 años, aproximadamente un panecillo menos por día, confería múltiples beneficios para la salud que se sabe que combaten el envejecimiento.
La fuente de la juventud parecía provenir de una proteína en la unión entre el metabolismo y la inmunidad, que caía precipitadamente después de hacer dieta.
“Dos años de restricción calórica modesta reprogramaron las vías en las células grasas que ayudan a regular la forma en que las mitocondrias generan energía, las respuestas antiinflamatorias del cuerpo y, potencialmente, la longevidad”, dijo el autor del estudio, el Dr. Eric Ravussin. “En otras palabras, la restricción calórica modifica muchas de las respuestas metabólicas e inmunitarias que aumentan la esperanza de vida y la salud”.
Yendo un paso más allá, el equipo desactivó la proteína en ratones. Sin reducir las calorías, los roedores tenían menos inflamación asociada con el envejecimiento y un timo, un órgano que produce células inmunitarias, y un metabolismo más eficiente en comparación con sus compañeros de edad similar.
«CR ha sido una piedra angular de la biología del envejecimiento durante décadas», dijo el Dr. Timothy Rhoads y Rozalyn Anderson de la Universidad de Wisconsin-Madison, que no participaron en el estudio. Pero, continuaron, aparte de las recomendaciones de estilo de vida, la clave es descubrir por qué funciona. Al hacerlo, podemos descubrir qué nos hace vulnerables al envejecimiento y qué nos hace más fuertes.
Hablemos de peso
CALERIE es un estudio considerable, tanto en objetivos como en alcance. El objetivo general es agregar datos sólidos al debate de larga duración: ¿la restricción calórica retarda los signos del envejecimiento en los humanos?
Luego viene el mapeo de la triple danza entre la «santa trinidad» de la restricción calórica, la inflamación y la inmunidad: ¿cómo se combinan para controlar la longevidad? Estudios anteriores encontraron que reducir las calorías en ratones a veces aumentaba su probabilidad de infección. Pero otros encontraron que redujo la inflamación relacionada con la edad para ayudar a preservar la función de los tejidos.
“Aquí nos preguntamos: ¿qué le está haciendo la restricción calórica a los sistemas inmunitario y metabólico y, si es realmente beneficiosa, cómo podemos aprovechar las vías endógenas [dentro del cuerpo] que imitan sus efectos en los humanos?”. dijo el autor principal Dr. Vishwa Deep Dixit.
El estudio tomó un camino notablemente diferente al de investigaciones anteriores sobre la restricción calórica. En lugar de comenzar con animales de laboratorio (moscas, gusanos y ratones), el equipo recurrió directamente a 200 voluntarios humanos. Primero establecieron la ingesta calórica de referencia en los participantes durante dos semanas utilizando un método estricto que calcula la cantidad de energía que ingieren en comparación con la cantidad que gastan. Luego, los participantes fueron seguidos durante seis meses con estrictas pruebas de laboratorio de su composición corporal, por ejemplo, músculo versus grasa. Establecido el punto de partida, algunos participantes redujeron sus calorías en aproximadamente un 14 por ciento durante los próximos dos años, mientras comían lo que quisieran.
Estudios previos en roedores que redujeron sus calorías a casi la mitad dieron como resultado un mejor funcionamiento de su timo y de las células T inmunitarias, así como una disminución de las moléculas que promueven la inflamación. El equipo preguntó si lo mismo era posible en humanos sin una caída drástica e insostenible de calorías.
Dijeron, en resumen, que sí.
Usando resonancia magnética, el equipo descubrió que la restricción calórica aumentaba el tamaño del timo en las personas que reducían las calorías. Una pequeña gota que se encuentra entre los pulmones, el timo es fundamental para la función inmunológica, actuando como cuna para poderosas células inmunológicas. Con la edad, el timo se reduce rápidamente de tamaño, lo que a su vez hace que los ancianos sean más propensos a las infecciones.
Para cuando los adultos sanos alcanzan los 40 años, explicó Dixit, aproximadamente el 70 por ciento del timo ya es graso y no funcional.
La restricción calórica no solo preservó el tamaño del timo; también aumentó su función, con una producción mucho mayor de células T inmunes. El grupo de control, que no restringió las calorías, no obtuvo ningún beneficio inmunológico o de timo. “Desde mi punto de vista, el hecho de que este órgano pueda rejuvenecerse es sorprendente porque hay muy poca evidencia de que esto suceda en humanos”, dijo Dixit. «Que esto sea posible es muy emocionante».
Hablemos por qué
Aparte de la función del timo, las personas que hicieron dieta también tenían menos neumáticos grasos alrededor de la cintura, mejores reacciones a la insulina y vasos sanguíneos y corazones más sanos.
Profundizando más, el equipo preguntó por qué reducir las calorías, algo relacionado con el metabolismo, tiene un impacto en el sistema inmunológico y una longevidad saludable. El trabajo en roedores mostró previamente que las células grasas son actores centrales en la inflamación y la inmunidad. Aquí, los investigadores tomaron muestras de las células grasas de los participantes y programaron exhaustivamente su expresión génica para observar las vías biológicas activadas.
Con la pantalla, ampliaron un gen, PLA2G7, que se apagó drásticamente con la dieta. Un bocado de un nombre, el gen es algo así como un misterio, con sus funciones biológicas no muy conocidas. Con un poco de investigación seria, el equipo encontró un papel tenue para la proteína que produce el gen: podría conectarse con moléculas grasas que provocan inflamación. Rodilla el gen, y puede apagar la inflamación pero encender la longevidad.
Probando su teoría, el equipo eliminó PLA2G7 en ratones. Sorprendentemente, eliminar este gen redujo drásticamente la obesidad en ratones con una dieta alta en grasas. Las moléculas inflamatorias que circulan en su sangre se redujeron drásticamente y los ratones tenían un mejor perfil inmunológico general. Equivalente a aproximadamente 70 años en la edad humana, el timo de los ratones ancianos floreció hasta la vejez, con una masa mucho mayor.
¿Reduzcamos las calorías?
CALERIE es uno de los primeros estudios que demuestra que reducir un poco las calorías en los seres humanos mejora las funciones que normalmente disminuyen con el envejecimiento. El ensayo, ahora en su segunda fase, no es perfecto: aún no conocemos las consecuencias a largo plazo de reducir las calorías o qué sucede cuando las personas vuelven a su ingesta calórica normal. Porque seamos realistas: es extremadamente difícil mantener una dieta durante años.
Pero lo que es más importante, el estudio abrió una ruta nueva y poco ortodoxa en la investigación de la longevidad. Al estudiar un tratamiento potencial en personas primero y luego probar el por qué en animales de laboratorio, en lugar de hacerlo al revés, ahora hemos descubierto un nuevo impulsor de los beneficios de la restricción calórica. Y si, como concluye el estudio, la clave para combatir el envejecimiento se encuentra en la intersección entre el metabolismo y el sistema inmunitario en los humanos, más “estudios similares pueden indicarnos objetivos potenciales que pueden mejorar la función inmunitaria, reducir la inflamación y, potencialmente, incluso mejorar la vida útil saludable. ”, dijo Dixit. Tal vez sin tener que hacer dieta.
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