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Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
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Delivery Pathways to the Lysosome01:36

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Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
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Mitochondria01:37

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Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
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Autophagic Cell Death01:18

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Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
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Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
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The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
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In Situ Immunofluorescent Staining of Autophagy in Muscle Stem Cells
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La autofagia mantiene el metabolismo y la función de las células madre jóvenes y viejas

Theodore T Ho1, Matthew R Warr1, Emmalee R Adelman2

  • 1Department of Medicine, Hem/Onc Division, The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA.

Nature
|February 28, 2017
PubMed
Resumen

La autofagia mantiene la estabilidad mediante la limpieza de las mitocondrias, preservando la regeneración de las células madre hematopoyéticas con la edad. La pérdida de autofagia acelera el envejecimiento al activar el metabolismo y deteriorar la función de las células madre.

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Área de la Ciencia:

  • Gerontología
  • Biología de las células madre
  • El metabolismo celular

Sus antecedentes:

  • El envejecimiento deteriora la capacidad regenerativa de las células madre hematopoyéticas (HSC), lo que contribuye a la enfermedad.
  • La autofagia, un proceso de reciclaje celular, es crucial para mantener la salud y la longevidad de los HSC.
  • El estrés metabólico tiene un impacto significativo en la función HSC y la auto-renovación.

Objetivo del estudio:

  • Investigar el papel de la autofagia en el envejecimiento y la regeneración de HSC.
  • Aclarar los mecanismos por los que la autofagia influye en el metabolismo y la función de los HSC.
  • Identificar estrategias para preservar el potencial de regeneración de la HSC en personas de edad avanzada.

Principales métodos:

  • Modelos de ratones con deficiencia de autofagia dirigida en los HSC.
  • Ensayos de contenido mitocondrial y actividad metabólica.
  • El análisis epigenético de los HSC.
  • Pruebas de regeneración de células madre a largo plazo.

Principales resultados:

  • La pérdida de autofagia en los HSC conduce a la acumulación mitocondrial y a un estado metabólico activado.
  • El deterioro de la autofagia provoca una diferenciación mieloide acelerada y una auto-renovación y regeneración reducidas de los HSC.
  • Un subconjunto de HSC envejecidos con alta autofagia mantiene un estado de reposo, bajo metabolismo y potencial regenerativo.
  • La autofagia suprime activamente el metabolismo de los HSC mediante la limpieza de las mitocondrias sanas, manteniendo la estructura del tallo.

Conclusiones:

  • La autofagia es esencial para suprimir el metabolismo de los HSC y preservar la capacidad de regeneración durante el envejecimiento.
  • El mantenimiento de la autofagia es crítico para mitigar el deterioro relacionado con la edad en la función HSC.
  • Dirigirse a la autofagia puede ofrecer una estrategia terapéutica para mejorar la regeneración de HSC en los ancianos.