mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases
Chronological age represents the greatest risk factor for many life-threatening diseases, including neurodegeneration, cancer, and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current efforts to tackle individual diseases may have little impact on the overall h...
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doaj-a5cf1d32624c4619910cb4a8a5e512f62020-11-24T22:15:42ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-08-01198232510.3390/ijms19082325ijms19082325mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related DiseasesHannah E. Walters0Lynne S. Cox1Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UKDepartment of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UKChronological age represents the greatest risk factor for many life-threatening diseases, including neurodegeneration, cancer, and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current efforts to tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing. Cellular senescence is an essentially irreversible proliferation arrest mechanism that has important roles in development, wound healing, and preventing cancer, but it may limit tissue function and cause widespread inflammation with age. The serine/threonine kinase mTOR (mechanistic target of rapamycin) is a regulatory nexus that is heavily implicated in both ageing and senescence. Excitingly, a growing body of research has highlighted rapamycin and other mTOR inhibitors as promising treatments for a broad spectrum of age-related pathologies, including neurodegeneration, cancer, immunosenescence, osteoporosis, rheumatoid arthritis, age-related blindness, diabetic nephropathy, muscular dystrophy, and cardiovascular disease. In this review, we assess the use of mTOR inhibitors to treat age-related pathologies, discuss possible molecular mechanisms of action where evidence is available, and consider strategies to minimize undesirable side effects. We also emphasize the urgent need for reliable, non-invasive biomarkers of senescence and biological ageing to better monitor the efficacy of any healthy ageing therapy.http://www.mdpi.com/1422-0067/19/8/2325mTORmTORC1mTORC2rapamycinrapaloguesrapalogsmTOR inhibitorssenescenceageingagingcancerneurodegenerationimmunosenescencesenolyticsbiomarkers |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hannah E. Walters Lynne S. Cox |
spellingShingle |
Hannah E. Walters Lynne S. Cox mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases International Journal of Molecular Sciences mTOR mTORC1 mTORC2 rapamycin rapalogues rapalogs mTOR inhibitors senescence ageing aging cancer neurodegeneration immunosenescence senolytics biomarkers |
author_facet |
Hannah E. Walters Lynne S. Cox |
author_sort |
Hannah E. Walters |
title |
mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases |
title_short |
mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases |
title_full |
mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases |
title_fullStr |
mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases |
title_full_unstemmed |
mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases |
title_sort |
mtorc inhibitors as broad-spectrum therapeutics for age-related diseases |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-08-01 |
description |
Chronological age represents the greatest risk factor for many life-threatening diseases, including neurodegeneration, cancer, and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current efforts to tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing. Cellular senescence is an essentially irreversible proliferation arrest mechanism that has important roles in development, wound healing, and preventing cancer, but it may limit tissue function and cause widespread inflammation with age. The serine/threonine kinase mTOR (mechanistic target of rapamycin) is a regulatory nexus that is heavily implicated in both ageing and senescence. Excitingly, a growing body of research has highlighted rapamycin and other mTOR inhibitors as promising treatments for a broad spectrum of age-related pathologies, including neurodegeneration, cancer, immunosenescence, osteoporosis, rheumatoid arthritis, age-related blindness, diabetic nephropathy, muscular dystrophy, and cardiovascular disease. In this review, we assess the use of mTOR inhibitors to treat age-related pathologies, discuss possible molecular mechanisms of action where evidence is available, and consider strategies to minimize undesirable side effects. We also emphasize the urgent need for reliable, non-invasive biomarkers of senescence and biological ageing to better monitor the efficacy of any healthy ageing therapy. |
topic |
mTOR mTORC1 mTORC2 rapamycin rapalogues rapalogs mTOR inhibitors senescence ageing aging cancer neurodegeneration immunosenescence senolytics biomarkers |
url |
http://www.mdpi.com/1422-0067/19/8/2325 |
work_keys_str_mv |
AT hannahewalters mtorcinhibitorsasbroadspectrumtherapeuticsforagerelateddiseases AT lynnescox mtorcinhibitorsasbroadspectrumtherapeuticsforagerelateddiseases |
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1725793692154855424 |