With TOR less is more: a key role for the conserved nutrient sensing TOR pathway in aging

By P. Kapahi, Di Chen, Aric N. Rogers, Subhash D. Katewa, P. Li, Emma L. Thomas, L. Kockel. Cell Metabolism, 2010

650 citations recorded by the source corpus.

TOR (target of rapamycin) is an evolutionarily conserved nutrient sensing protein kinase that regulates growth and metabolism in all eukaryotic cells. Studies in flies, worms, yeast and mice support the notion that the TOR signaling network plays a pivotal role in modulating aging. TOR is emerging as the most robust mediator of the protective effects of various forms of dietary restriction (DR), which has been shown to extend lifespan and slow the onset of certain age-related diseases across species. Here we discuss how modulating the TOR signaling network slows aging by affecting a number of downstream processes including mRNA translation, autophagy, endoplasmic reticulum (ER) stress signaling, stress responses and metabolism. Identifying the mechanisms by which the TOR signaling network works as a pacemaker of aging is a major challenge in the field and may help identify potential drug targets for age–related diseases thereby facilitating healthful lifespan extension in humans.

Subfields: Aging, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/994e38062b7383e66dc6f1c5d83072e743c216e1

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

1. Guido Kroemer
2. Guillermo Mariño
3. David M. Sabatini
4. Nir Barzilai
5. T. Blackwell
6. D. Rubinsztein

In Epidemiology

1. Guido Kroemer
2. Guillermo Mariño
3. David M. Sabatini
4. D. Rubinsztein
5. M. Laplante
6. Michael N. Hall
7. R. Loewith
8. Beth Levine

In Molecular Biology

1. David M. Sabatini
2. M. Laplante
3. Michael N. Hall
4. D. Rubinsztein
5. R. Loewith
6. Guido Kroemer
7. Guillermo Mariño
8. Nir Barzilai

Citations in the corpus

• Target of Rapamycin (TOR) in Nutrient Signaling and Growth Control (2011, background): “Epistasis studies have led many to believe that this is due to reduced TORC1 signaling (reviewed in Weindruch and Walford 1988; Kapahi et al. 2010; Zoncu et al. 2010, 2011; Kaeberlein and Kennedy 2011).”
• mTOR signaling in growth control and disease (2012, background): “The high activation of mTORC1 in the muscle of obese and high-fat-fed rodents drives S6K1-mediated feedback inhibition of insulin signaling, which reduces glucose uptake by themuscle and contributes to systemic insulin resistance (Figure 4C) (Khamzina et al., 2005; Um et al., 2004).”
• The Critical Role of Metabolic Pathways in Aging (2012, background): “Inhibition of the mTOR signaling pathway by genetic or pharmacological intervention extends life span in invertebrates, including yeast, nematodes, and fruit flies (64).”
• Autophagy and aging. (2011, background): “Moreover, TORC1 inhibition has major effects on protein translation (Kapahi et al., 2010), raising the question of whether mTOR inhibition enhances longevity due to the induction of autophagy or whether this effect also involves autophagy-unrelated effects.”
• TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO (2012, background): “DAF-16 and SKN-1 regulate genes that protect against environmental, metabolic, and proteotoxic stress, and promote longevity in various species (Kenyon, 2010; Kwon et al., 2010; Li et al., 2011; Oliveira et al., 2009; Sykiotis and Bohmann, 2010; Tullet et al., 2008).”