A research team has identified a key protein that may shed light on how to reverse the aging process using the adult stem cell of skeletal muscle (or muscle stem cells, MuSCs) as a model system. The discovery paves the way for the possible future development of therapeutic interventions for aging-related diseases and various mitochondrial diseases.
During human aging, cells undergo a process of cellular senescence, where they no longer divide but do not die, acting like "zombie cells," accumulating in the human body, causing cellular damage, and contributing to age-related defects. Importantly, the ability of cells to maintain healthy functions relies upon their capacity to generate chemical energy, of which mitochondria, the powerhouse of the cell, plays a vital role.
However, as cells age, their ability to produce sufficient energy declines. The loss of mitochondrial activity has been associated with senescence in many tissues. Proper mitochondrial functions are important for MuSCs to repair damaged skeletal muscle following injury and to maintain the resident stem cell pool for future regeneration. Yet, the signaling pathways which regulate mitochondrial metabolism during aging remain unclear.
A laboratory group recently identified the role of CPEB4, an mRNA-binding protein, in maintaining mitochondrial metabolism, by upregulating the biosynthesis of mitochondrial proteins, thus maintaining sufficient energy output. In addition, the team showed that the levels of CPEB4 protein decreased in various aging murine tissues, particularly skeletal muscle.
They also observed that aged muscle shows signs of senescence following muscle injury, as shown by the increased presence of the senescence marker, senescence-associated β-galactosidase (SA-β-gal), compared to adult muscle. Importantly, their research demonstrated that restoring CPEB4 expression in aged MuSCs increased mitochondrial protein production, boosted energy production, and impressively protected against cellular senescence. Of note, the transplantation of CPEB4 re-expressing MuSCs into geriatric recipient mice led to improved muscle repair. Similarly, CPEB4 expression in various human cell lines also protected against cellular senescence.
The senior author comments, "Our findings highlight the importance of maintaining mitochondrial functions and its proteome by mRNA-binding proteins in muscle stem cells. More importantly, our study provides new insights into the diagnostic and therapeutic potential of CPEB4 to rescue mitochondrial defects and reverse cellular senescence during aging. Our work also lays the groundwork to study further the feasibility of developing CPEB4 as a potential therapeutic target for various mitochondrial diseases such as Leigh Syndrome."
These findings were recently published in Developmental Cell.
https://www.cell.com/developmental-cell/fulltext/S1534-5807(23)00244-7
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Frestoration-of-cpeb4&filter=22
Restoration of CPEB4 prevents muscle stem cell senescence during aging
- 1,262 views
- Added
Latest News
Protein that helps COVID-19…
By newseditor
Posted 26 Jul
Spinal Muscular Atrophy (SM…
By newseditor
Posted 26 Jul
Link between bowel movement…
By newseditor
Posted 26 Jul
Inhibition of IL-11 signall…
By newseditor
Posted 25 Jul
Brain changes linked to obe…
By newseditor
Posted 25 Jul
Other Top Stories
Deep-sleep brain waves predict blood sugar control
Read more
Extracellular cytochrome nanowires appear to be ubiquitous in microbes
Read more
Distinct connectivity patterns for depression associated with traum…
Read more
Antisense therapy restores fragile X protein production in human cells
Read more
Biomarker for allergic reaction in kidneys identified!
Read more
Protocols
A systems biology approach…
By newseditor
Posted 24 Jul
quantms: a cloud-based pipe…
By newseditor
Posted 22 Jul
Emerging tools and best pra…
By newseditor
Posted 19 Jul
Directly selecting cell-typ…
By newseditor
Posted 17 Jul
PUFFFIN: an ultra-bright, c…
By newseditor
Posted 16 Jul
Publications
Hepatocyte-intrinsic SMN de…
By newseditor
Posted 26 Jul
Aberrant bowel movement fre…
By newseditor
Posted 26 Jul
A pseudoautosomal glycosyla…
By newseditor
Posted 26 Jul
Microglia protect against a…
By newseditor
Posted 26 Jul
Rigor and reproducibility i…
By newseditor
Posted 26 Jul
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar