!-- Google tag (gtag.js) -->

How is the cellular mechanism that can regulate aging and fertility

Nucleolar size is a highly predictive marker for longevity Photo: Freepik.
Nucleolar size is a highly predictive marker for longevity Photo: Freepik.

The gradual deterioration of the nuclear architecture is a common denominator aging y de muchas patologías relacionados con la edad en diversas especies, including la humana. In particular, aging is characterized by a substantial expansion of the nucleus, the largest structure inside the nucleus of the cells. Por el contrario, la longevity y extensión de la vida se han asociado con un tamaño nucleolar pequeno.

But now, a research of the Instituto de Biología Molecular y Biotecnología (IMBB) of the Hellas Research and Technology Foundation (FORTH) in Greece, publicada en la revista Nature Agingreveals a fundamental quality control mechanism that operates in cells to protect the integrity and function of the nucleus.

Al maintaining nuclear homeostasis, that is, the tendency to maintain a stable and relatively constant internal environment, produces a fundamental contribution to longevity and fertility.

The investigation showed that the cells necessary for reproduction are protected by autophagy (iStock)
The investigation showed that the cells necessary for reproduction are protected by autophagy (iStock)

The investigators of IMBB, Margherita-Elena Papandreou and Georgios Konstantinides, directed by Nektarios Tavernakis, Professor of the Faculty of Medicine of the University of Crete in Greece and President of the Board of FORTH, discovered that recycling nuclear components y nucleolares a través de la autophagia (proceso en el que la célula decompone y destruye proteins viejas, dañadas o abnormales, y otras sustancias en su liquido interior) retrasa el vejecimiento celular y maintaine la immortalidad de las célula germinales necessaria para la reproduction.

The nucleus is the central key of all eukaryotic cells: it contains the genetic material (DNA) que determina la identidad y funcio celular. Con el envejecimiento y en las célús cancerosas, la ultraestructura del núcleo cambia drásticamente.

Un progresivo y marcado en la arquitectura del núcleo es una characteristica comun y conservadora de la progeria, una rara enfermedad genética que produce un vejecimiento rápido en los niños, y muchas otras enfermedades asociados con el envejecimiento.

Autophagy is the process by which the cell can destroy its own contents by enclosing them in a membrane and transferring them to a
Autophagy is the process by which the cell can destroy its own contents by enclosing them in a membrane and transferring them to a “recycling compartment”, called the lysosome, for degradation.

In addition, the progeroid syndromes (for example, the Hutchinson-Gilford, Werner, Bloom and Cockayne syndromes, etc.) from the ribosome, which is the protein synthesis machine in the cell.

Los mechanisms moleculares y celulares que provocan los cambios siguen sin estar claros. Tampoco lo están si tales cambios son simplemente una consecuencia del proceso de envejecimiento y las patologías relacionados con la edad, o si juegan un papel causal en la progeria y el empeoramiento del envejecimiento.

La preservación de la ultraestructura nuclear y el processing del material nuclear son necesarios para la homeostasis celular y del organismo. Su focalización y degradación se realiza mediante nucleophagy, a selective type of autophagy that serves as a quality control mechanism for the nuclei. In fact, aberrant nucleophagy is associated with a wide range of pathologies, including DNA damage, cancer and neurodegeneration.

The small size of the nucleus is associated with longevity and interventions to prolong life (Getty Images)
The small size of the nucleus is associated with longevity and interventions to prolong life (Getty Images)

Sin embargo, se desconoce la participation de los mechanisms autofágicos en el mantenimiento de la structure y funcio nuclear durante el envejecimiento. Aún queda una pregunta abierta related to las vías de señalización y las intervenciones, como la señalización de insulin/IGF1 y la restricción dietética, que son modulators characterized de la esperanza de vida en organismes que van desde nematodos hasta primates. Se desconoce si estas vías interactúan y cómo lo hacen con los procesos moleculares que forman el núcleo y determinan el tamaño y la funcion del nucléolo durante el envejecimiento.

Using two experimental organisms, the nematode Caenorhabditis elegans and a mouse, the researchers at IMBB proposed answering these key questions. En su estudio informan que la giant nuclear envelope, anchor protein, Nesprin-2, y su ortholog Caenorhabditis elegans ANC-1 son importantes reguladores de la nucleofagia.

The function of Nesprin-2/ANC-1 is maintaining a small nucleus size, which is the common denominator of various longevity prolongation regimens. In addition, it prevents abnormalities in the nuclear form and the accumulation of sheets, the main structural component of the nuclear sheet.

The researchers affirmed that the maintenance of the architecture and the nuclear operation requires continuous and highly regulated reprocessing of defective or damaged nuclear components (Getty Images)
The researchers affirmed that the maintenance of the architecture and the nuclear operation requires continuous and highly regulated reprocessing of defective or damaged nuclear components (Getty Images)

In addition, the elimination of aberrant germinal cells of C. elegans during its differentiation in the reproductive system of the animal, the gonad, requires nucleophagy mediated by ANC-1. In particular, the interruption of this route of elimination provokes structures similar to tumors in the germinal line of C. elegans and progressive sterility during several generations, the phenomenon of death in the germinal line.

De manera similar, la eliminação genetica de Nesprin 2 en ratones hembra causa cáncer de ovario, lo que indica que las vías moleculares relevantes se conservan evolutivamente en tipos distantes. De hecho, los polymorphismos del homólogo humano de nesprin, Syne2, están asociados con la infertilidad ovarica en las mujeres. Estos resultados indican que la autophagia selectiva del material nuclear es un importante determinante del vejecimiento somático y la immortalidad de la línea germinal bajo estres y puede usarse para tratar la infertility en humanos.

“Siempre nos ha interesado la dichotomía entre dos phenomenos fundamentales de la biology diametrically opposed: la mortality del soma y la immortalidad de la línea germinal y nos embarcarnos en un viaje exploratorio para abordar estos problemas” affirmed Nektarios Tavernarakis.

“The nuclear morphology of somatic cells deteriorates with ageing,” said Nektarios Tavernarakis, a scientist who formed part of the investigation.

“Our hypothesis was that the homeostatic mechanism effectively maintains the structure of the nuclei of the germinal cells while it falls during aging, in the soma. Nos sorprendió descubrir que el reciclaje autofágico de material nuclear es un factor importante que preserve la arquitectura nuclear y limita el tamaño del nucléolo. Curiously, the nucleophagy interacts with the signal transduction pathways that prolong life, highlighting the complex molecular mechanisms that influence aging”, declared Nektarios Tavernarakis.

This new investigation reveals that nucleophagy is a molecular mechanism that integrates various physiological signals to influence nuclear architecture and homeostasis.

In addition, it identifies nucleophagy as a posterior effector of low insulin/IGF1 signaling and dietary restriction of somatic aging.

Científicos descubrieron que la nucleofagia retrasa el envejecimiento
Científicos descubrieron que la nucleofagia retrasa el envejecimiento

Los members de la familia Nesprin actua como reguladores clave de la nucleofagia. The interruption of the recycling of nuclear material through nucleophagy reduces the tolerance of stress, reduces the hope of life of animals and provokes the progressive death of the germinal line.

Por lo tanto, the nucleophagy is an important mechanism for the longevity of the soma and the immortality of the germline, which promotes youth and delays aging under stress while maintaining the nuclear structure and preventing nuclear expansion that can boost aging in the seres humanos

Seguir leyendo

Leave a Comment

Your email address will not be published. Required fields are marked *

Scroll to Top