Abstract:
:Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular communication, loss of proteostasis, cellular senescence and adult stem cell exhaustion. However, whether and how these instigators of aging interrelate or whether they have one root cause is currently largely unknown. Rare human progeroid syndromes and corresponding mouse mutants with resolved genetic defects highlight the dominant importance of genome maintenance for aging. A second class of aging-related disorders reveals a cross connection with metabolism. As genome maintenance and metabolism are closely interconnected, they may constitute the main underlying biology of aging. This review focuses on the role of genome stability in aging, its crosstalk with metabolism, and options for nutritional and/or pharmaceutical interventions that delay age-related pathology.
journal_name
Annu Rev Pharmacol Toxicoljournal_title
Annual review of pharmacology and toxicologyauthors
Vermeij WP,Hoeijmakers JH,Pothof Jdoi
10.1146/annurev-pharmtox-010814-124316subject
Has Abstractpub_date
2016-01-01 00:00:00pages
427-45eissn
0362-1642issn
1545-4304journal_volume
56pub_type
杂志文章,评审abstract::This essay is an account of the author's experience in trying to interpret the action of drugs as seen in in vitro bioassays. The central theme is how the development of simple mathematical models has assisted in the interpretation of drug actions. Starting from encounters with partial agonists, the essay describes th...
journal_title:Annual review of pharmacology and toxicology
pub_type: 传,历史文章,杂志文章,评审
doi:10.1146/annurev.pa.36.040196.000245
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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doi:10.1146/annurev.pharmtox.39.1.399
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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更新日期:2006-01-01 00:00:00
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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更新日期:1998-01-01 00:00:00
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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更新日期:1997-01-01 00:00:00
abstract::Research spanning (genetically engineered) animal models, healthy volunteers, and sleep-disordered patients has identified the neurotransmitters and neuromodulators dopamine, serotonin, norepinephrine, histamine, hypocretin, melatonin, glutamate, acetylcholine, γ-amino-butyric acid, and adenosine as important players ...
journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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更新日期:2004-01-01 00:00:00
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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abstract::Development of scientific creativity is often tied closely to mentorship. In my case, two years with Julius Axelrod, the sum total of my research training, was transformative. My mentoring generations of graduate students and postdoctoral fellows has been as nurturing for me as it has been for them. Work in our lab ov...
journal_title:Annual review of pharmacology and toxicology
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更新日期:2017-01-06 00:00:00