Related Experiment Video

Updated: Aug 13, 2025

Assessing Lysosomal Alkalinization in the Intestine of Live Caenorhabditis elegans
06:18

Assessing Lysosomal Alkalinization in the Intestine of Live Caenorhabditis elegans

Published on: April 13, 2018

6.1K

Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence

Myeong Uk Kuk1, Haneur Lee1, Eun Seon Song1

  • 1Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea.

Experimental Gerontology
|January 19, 2023
PubMed

Insights

This study identifies GDC0068 as a potential treatment to reverse cellular senescence. It restores lysosomal and mitochondrial function by modulating AKT activity, offering hope for aging-related diseases.

Area of Science:

  • Cellular Biology
  • Aging Research
  • Molecular Medicine

Background:

  • Cellular senescence, characterized by organelle dysfunction, drives aging and related diseases.
  • Activation of serine/threonine protein kinases (AKT1, AKT2, AKT3) is a key driver of oncogene-induced senescence.

Purpose of the Study:

  • To evaluate AKT inhibitors for their potential to ameliorate cellular senescence.
  • To elucidate the mechanism by which senescence can be reversed.

Main Methods:

  • Screening of twelve AKT inhibitors.
  • Assessment of lysosomal function, including lysosomal mass and autophagic flux.
  • Evaluation of mitochondrial function and removal of dysfunctional mitochondria.

Main Results:

  • GDC0068 was identified as a promising agent for ameliorating senescence.
  • GDC0068 treatment led to lysosomal functional recovery, indicated by reduced lysosomal mass and increased autophagic flux.
  • Restoration of lysosomal function by GDC0068 promoted the clearance of dysfunctional mitochondria, thereby restoring mitochondrial function.

Conclusions:

  • GDC0068 effectively ameliorates senescence by restoring lysosomal and mitochondrial function.
  • Modulation of AKT activity represents a novel therapeutic strategy for reversing cellular senescence.
  • The findings reveal a unique mechanism involving lysosomal and mitochondrial repair in senescence recovery.
Keywords:
AKTGDC0068LysosomeMitochondriaSenescence amelioration

More Related Videos

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy09:29

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy

Published on: May 4, 2016

7.2K
Dual-color Correlative Light and Electron Microscopy for the Visualization of Interactions between Mitochondria and Lysosomes10:25

Dual-color Correlative Light and Electron Microscopy for the Visualization of Interactions between Mitochondria and Lysosomes

Published on: September 27, 2024

690

Related Concept Videos

Mitochondria01:37

Mitochondria

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,...
14.1K
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

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.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.7K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.8K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
14.8K
Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.9K
Autophagy01:27

Autophagy

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,...
4.4K