Aging and disease

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01 February 2010. VOL 1, ISSUE 2 Previous Issue Next Issue

Modern Biological Theories of Aging
Kunlin Jin

2010, 1 (2): 72-74

PDF (291KB)
Signaling and Damaging Functions of Free Radicals in Aging—Free Radical Theory, Hormesis, and TOR
Igor Afanas’ev

2010, 1 (2): 75-88

PDF (744KB)
Dietary Restriction and Aging in Rodents: a Current View on its Molecular Mechanisms
Isao Shimokawa, Lucas S. Trindade

2010, 1 (2): 89-107

PDF (1386KB)
Aging and the Mammalian Regulatory Triumvirate
C. David Rollo

2010, 1 (2): 105-138

PDF (953KB)
Old age as a privilege of the “selfish ones”
Mladen Davidovic, Goran Sevo, Petar Svorcan, Dragoslav P. Milosevic, Nebojsa Despotovic, Predrag Erceg

2010, 1 (2): 139-146

PDF (431KB)
Insulin, IGF-1 and longevity
Diana van Heemst

2010, 1 (2): 147-157

PDF (637KB)
Aging and Neurogenesis, a Lesion from Alzheimer’s Disease
Philippe Taupin

2010, 1 (2): 158-168

PDF (651KB)

Cover Illustration

01 February 2010. Vol.1 No.2
A temporal framework linking circadian rhythms and clocks to aging rates identifies a specific window of target of rapamycin (TOR) signaling associated with growth hormone (GH) and insulin-like growth factor (IGF-1) (largely exclusive of insulin) in early sleep. IGF-1 signaling is released by growth hormone secretory peaks and downregulation of IGF-1 binding protein-1 resulting in activation of the mitogen activated protein kinase/extracellular signal response kinase (MAPK/ERK) and phosphoinositide 3-kinase-protein kinase B (PI3K-PKB/Akt) signaling pathways. Phosphorylation of Akt activates TOR which mediates the protein synthesis and growth functions of the GH axis. TOR activity is also associated with downregulated stress resistance, faster aging and reduced lifespan. IGF-1 signaling is terminated by falling GH and upregulation of IGF-1 binding proteins mediated by somatostatin and rising corticosteroids in later sleep. This suppresses PI3K-Akt signaling, thus activating the forkhead transcription factors (FOXOs) and stress-resistance pathways involved in promoting longevity. Thus, sleep appears to encompass both pathways currently identified as most relevant to aging and they toggle successively on the phosphorylation status of Akt. I propose a modified version of Pearl’s rate of living theory emphasizing the hard-wired antagonism of growth (TOR) and stress resistance (FOXO). The sleep association of TOR and FOXO in temporally separated windows and their sequential temporal deployment may change much of the way we think about aging and how to manipulate it.

[Detail]

Cover Illustration

A temporal framework linking circadian rhythms and clocks to aging rates identifies a specific window of target of rapamycin (TOR) signaling associated with growth hormone (GH) and insulin-like growth factor (IGF-1) (largely exclusive of insulin) in early sleep. IGF-1 signaling is released by growth hormone secretory peaks and downregulation of IGF-1 binding protein-1 resulting in activation of the mitogen activated protein kinase/extracellular signal response kinase (MAPK/ERK) and phosphoinositide 3-kinase-protein kinase B (PI3K-PKB/Akt) signaling pathways. Phosphorylation of Akt activates TOR which mediates the protein synthesis and growth functions of the GH axis. TOR activity is also associated with downregulated stress resistance, faster aging and reduced lifespan. IGF-1 signaling is terminated by falling GH and upregulation of IGF-1 binding proteins mediated by somatostatin and rising corticosteroids in later sleep. This suppresses PI3K-Akt signaling, thus activating the forkhead transcription factors (FOXOs) and stress-resistance pathways involved in promoting longevity. Thus, sleep appears to encompass both pathways currently identified as most relevant to aging and they toggle successively on the phosphorylation status of Akt. I propose a modified version of Pearl’s rate of living theory emphasizing the hard-wired antagonism of growth (TOR) and stress resistance (FOXO). The sleep association of TOR and FOXO in temporally separated windows and their sequential temporal deployment may change much of the way we think about aging and how to manipulate it.