mTOR is a key modulator of ageing and age-related disease

By Simon C. Johnson, P. Rabinovitch, Matt Kaeberlein. Nature, 2013

1,621 citations recorded by the source corpus.

Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of 'when' rather than 'if'. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.

Subfields: Aging, Endocrine and Autonomic Systems, Physiology

View Paper: https://www.semanticscholar.org/paper/12e7b75d0f15ca368e0e7884eed2803ea8ac5d2b

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In Aging

In Endocrine and Autonomic Systems

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Citations in the corpus

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming (2016, positive): “The last decade of scientiﬁc research has dramatically improved our understanding of the aging process (Johnson et al., 2013; Kenyon, 2010; Riera et al., 2016).”
SIRT1 and other sirtuins in Metabolism (2013, background): “N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript Outstanding questions • Several pathways, including sirtuins, insulin signaling, TOR, and AMP kinase are proposed to mediated CR.”
Promoting Health and Longevity through Diet: from Model Organisms to Humans (2015, positive): “Dietary protein intake is an important regulator of the IGF-1/mTOR network (Efeyan et al, 2012).”
Human Ageing Genomic Resources: new and updated databases (2017, background): “Examples of these include MYC, an oncogene mainly studied in the context of cancer (8), MTOR, a regulator of several cellular processes which was found to play a role in ageing in various model organisms (9), and TP53, a well-known tumour suppressor (10) (Figure 1).”
The hallmarks of aging. (2013, background): “Genetic downregulation of mTORC1 activity in yeast, worms, and flies extends longevity and attenuates further longevity benefits from DR, suggesting that mTOR inhibition phenocopies DR (Johnson et al., 2013).”
The PI3K pathway in human disease (2017, positive): “The evolutionarily conserved role of PI3K and mTOR in organismal aging also provides new opportunities to extend lifespan and, more importantly, healthspan through partial pathway inhibition (Johnson et al., 2013; Pan and Finkel, 2017; Selman et al., 2009; Wu et al., 2013).”
β-Hydroxybutyrate (2017, positive): “This is one of several examples of intersections between BHB, its signaling effects, and mTOR/rapamycin, a canonical longevity-regulating pathway (55).”
Metformin as a Tool to Target Aging (2016, positive): “More importantly, these pathways have been evaluated in mammalian models, in which health span and lifespan have been extended by genetic manipulation or drugs (Johnson et al., 2013).”
The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates (2018, background): “In fact, an inhibition of this pathway extends the lifespan of many species (84).”