The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review.
Osteoarthritis
Osteosarcopenia
Rapalogues
Rapamycin
Rheumatoid arthritis
mTOR
Journal
Aging clinical and experimental research
ISSN: 1720-8319
Titre abrégé: Aging Clin Exp Res
Pays: Germany
ID NLM: 101132995
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
30
03
2022
accepted:
23
06
2022
pubmed:
22
7
2022
medline:
9
11
2022
entrez:
21
7
2022
Statut:
ppublish
Résumé
Preclinical studies have shown a therapeutic role of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1) inhibition with rapamycin and its analogues (rapalogues) on several age-related musculoskeletal disorders (MSKD). However, the applicability to humans of these findings is unknown. To assess the efficacy of rapalogues on age-related MSKD in humans. We conducted a systematic review according to the PRISMA guidelines. MEDLINE, EMBase, EMCare, and Cochrane Central Registry of Controlled Trials were searched for original studies examining the effects of rapalogues on outcomes linked to the age-related MSKD in humans. This review is registered in the PROSPERO database (University of New York; registration number CRD42020208167). Fourteen studies met the inclusion criteria and were analyzed. The effect of rapamycin and other rapalogues, including everolimus and temsirolimus, on bone, muscle and joints have been evaluated in humans; however, considerable variability concerning the subjects' age, inclusion criteria, and drug administration protocols was identified. In bone, the use of rapamycin is associated with a decrease in bone resorption markers dependent on osteoclastic activity. In muscle, rapamycin and rapalogues are associated with a reduction in muscle protein synthesis in response to exercise. In the context of rheumatoid arthritis, rapamycin and rapalogues have been associated with clinical improvement and a decrease in inflammatory activity. Although there are studies that have evaluated the effect of rapamycin and rapalogues on MSKD in humans, the evidence supporting its use is still incipient, and the clinical implication of these results on the development of osteoporosis, sarcopenia, or osteosarcopenia has not been studied, opening an interesting field for future research.
Sections du résumé
BACKGROUND
BACKGROUND
Preclinical studies have shown a therapeutic role of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1) inhibition with rapamycin and its analogues (rapalogues) on several age-related musculoskeletal disorders (MSKD). However, the applicability to humans of these findings is unknown.
OBJECTIVE
OBJECTIVE
To assess the efficacy of rapalogues on age-related MSKD in humans.
METHODS
METHODS
We conducted a systematic review according to the PRISMA guidelines. MEDLINE, EMBase, EMCare, and Cochrane Central Registry of Controlled Trials were searched for original studies examining the effects of rapalogues on outcomes linked to the age-related MSKD in humans. This review is registered in the PROSPERO database (University of New York; registration number CRD42020208167).
RESULTS
RESULTS
Fourteen studies met the inclusion criteria and were analyzed. The effect of rapamycin and other rapalogues, including everolimus and temsirolimus, on bone, muscle and joints have been evaluated in humans; however, considerable variability concerning the subjects' age, inclusion criteria, and drug administration protocols was identified. In bone, the use of rapamycin is associated with a decrease in bone resorption markers dependent on osteoclastic activity. In muscle, rapamycin and rapalogues are associated with a reduction in muscle protein synthesis in response to exercise. In the context of rheumatoid arthritis, rapamycin and rapalogues have been associated with clinical improvement and a decrease in inflammatory activity.
CONCLUSION
CONCLUSIONS
Although there are studies that have evaluated the effect of rapamycin and rapalogues on MSKD in humans, the evidence supporting its use is still incipient, and the clinical implication of these results on the development of osteoporosis, sarcopenia, or osteosarcopenia has not been studied, opening an interesting field for future research.
Identifiants
pubmed: 35861940
doi: 10.1007/s40520-022-02190-0
pii: 10.1007/s40520-022-02190-0
pmc: PMC9637607
doi:
Substances chimiques
TOR Serine-Threonine Kinases
EC 2.7.11.1
Sirolimus
W36ZG6FT64
Everolimus
9HW64Q8G6G
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Types de publication
Systematic Review
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2317-2333Informations de copyright
© 2022. The Author(s).
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