Apoptotic metabolites ameliorate bone aging phenotypes via TCOF1/FLVCR1-mediated mitochondrial homeostasis.
J Nanobiotechnology
; 22(1): 549, 2024 Sep 06.
Article
in En
| MEDLINE
| ID: mdl-39237990
ABSTRACT
Over 50 billion cells undergo apoptosis each day in an adult human to maintain tissue homeostasis by eliminating damaged or unwanted cells. Apoptotic deficiency can lead to age-related diseases with reduced apoptotic metabolites. However, whether apoptotic metabolism regulates aging is unclear. Here, we show that aging mice and apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) mice exhibit decreased apoptotic levels along with increased aging phenotypes in the skeletal bones, which can be rescued by the treatment with apoptosis inducer staurosporine (STS) and stem cell-derived apoptotic vesicles (apoVs). Moreover, embryonic stem cells (ESC)-apoVs can significantly reduce senescent hallmarks and mtDNA leakage to rejuvenate aging bone marrow mesenchymal stem cells (MSCs) and ameliorate senile osteoporosis when compared to MSC-apoVs. Mechanistically, ESC-apoVs use TCOF1 to upregulate mitochondrial protein transcription, resulting in FLVCR1-mediated mitochondrial functional homeostasis. Taken together, this study reveals a previously unknown role of apoptotic metabolites in ameliorating bone aging phenotypes and the unique role of TCOF1/FLVCR1 in maintaining mitochondrial homeostasis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aging
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Apoptosis
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Mesenchymal Stem Cells
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Homeostasis
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Mitochondria
Limits:
Animals
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Humans
Language:
En
Journal:
J Nanobiotechnology
Year:
2024
Document type:
Article
Affiliation country:
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