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Updated: May 15, 2026

Imaging and Quantifying Mitochondrial Morphology in C. elegans During Aging
Published on: January 17, 2025
Ceramide and its transport protein (CERT) contribute to deterioration of mitochondrial structure and function in
Loro L Kujjo1, Beth M Acton, Guy A Perkins
1Department of Human Anatomy, Michigan State University, East Lansing, MI 48824, USA.
Abstract:
In women as well as in mice, oocytes exhibit decreased developmental potential (oocyte quality) with advanced age. Our current data implicate alterations in the levels of oocyte ceramide and associated changes in mitochondrial function and structure as being prominent elements contributing to reduced oocyte quality. Both ROS levels and ATP content were significantly reduced in aged oocytes. The decreased in ROS levels are of intrigue because it is contrary to what has been previously reported. Lowered levels of both ROS and ATP indicate diminished mitochondrial function that was accompanied by alterations in mitochondrial structure. Interestingly, developmental potential of old oocytes was improved by microinjection of mitochondria isolated from young oocytes. Co-treatment of aged oocytes with ceramide and a cytoplasmic lipid carrier (l-carnitine) improved both mitochondrial morphology and function, and totally rescued spontaneous in vitro fragmentation. In addition, ceramide localization was altered in old oocytes possibly due to downregulation of the ceramide transport protein (CERT). However, knockdown of CERT alone was not sufficient to increase young oocyte's susceptibility to death, because the sequential manipulation of ceramide levels (its chronic decrease, followed by downregulation of CERT, and finally a ceramide spike) were all necessary to replicate the aging phenotype. These results indicate that oocyte aging is due to a multiplicity of events; and that with increasing biological age, changes in levels of both ceramide and its transport protein contribute to deterioration of oocyte mitochondrial structure and function. Hence, those changes may represent potential targets to manipulate when attempting to ameliorate aging phenotypes in germ cells.
Insights
Aging oocytes show reduced quality due to ceramide changes impacting mitochondria. Restoring ceramide and mitochondrial function can improve oocyte developmental potential in aging.
Area of Science:
- Reproductive Biology
- Cellular Aging
- Mitochondrial Biology
Background:
- Oocyte quality and developmental potential decline with advanced maternal age in women and mice.
- Previous research has not fully elucidated the molecular mechanisms underlying age-related oocyte quality decline.
Purpose of the Study:
- To investigate the role of ceramide and mitochondrial dysfunction in age-related oocyte quality decline.
- To identify potential therapeutic targets for ameliorating aging phenotypes in oocytes.
Main Methods:
- Analysis of ceramide levels, mitochondrial function (ROS, ATP), and structure in young and aged oocytes.
- Mitochondrial transplantation experiments from young to aged oocytes.
- Co-treatment of aged oocytes with ceramide and l-carnitine.
- Investigation of ceramide transport protein (CERT) role using knockdown techniques.
Main Results:
- Aged oocytes exhibited decreased ceramide levels, reduced ROS and ATP, and altered mitochondrial morphology and function.
- Mitochondrial transplantation improved aged oocyte developmental potential.
- Ceramide and l-carnitine co-treatment rescued mitochondrial function and prevented fragmentation in aged oocytes.
- Downregulation of CERT and specific ceramide level manipulations replicated the aging phenotype.
Conclusions:
- Age-related oocyte deterioration involves alterations in ceramide levels and mitochondrial function.
- Changes in ceramide and CERT contribute to mitochondrial structural and functional decline in aging oocytes.
- Targeting ceramide metabolism and mitochondrial health may offer strategies to improve oocyte quality.
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