Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low caloric intake (caloric restriction) can lengthen the life span of a wide range of animals and possibly even of humans. To understand better how caloric restriction lengthens life span, we used genetic methods and criteria to investigate its mechanism of action in the nematode Caenorhabditis elegans. Mutations in many genes (eat genes) result in partial starvation of the worm by disrupting the function of the pharynx, the feeding organ. We found that most eat mutations significantly lengthen life span (by up to 50%). In C. elegans, mutations in a number of other genes that can extend life span have been found. Two genetically distinct mechanisms of life span extension are known: a mechanism involving genes that regulate dauer formation (age-1, daf-2, daf-16, and daf-28) and a mechanism involving genes that affect the rate of development and behavior (clk-1, clk-2, clk-3, and gro-1). We find that the long life of eat-2 mutants does not require the activity of DAF-16 and that eat-2; daf-2 double mutants live even longer than extremely long-lived daf-2 mutants. These findings demonstrate that food restriction lengthens life span by a mechanism distinct from that of dauer-formation mutants. In contrast, we find that food restriction does not further increase the life span of long-lived clk-1 mutants, suggesting that clk-1 and caloric restriction affect similar processes.
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PMID:The genetics of caloric restriction in Caenorhabditis elegans. 978 46

The dauer larva is an alternative larval stage in Caenorhabditis elegans which allows animals to survive through periods of low food availability. Well-fed worms live for about three weeks, but dauer larvae can live for at least two months without affecting post-dauer lifespan. Mutations in daf-2 and age-1, which produce a dauer constitutive (Daf-C) phenotype, and in clk-1, which are believed to slow metabolism, markedly increase adult lifespan. Here we show that a ctl-1 mutation reduces adult lifespan in otherwise wild-type animals and eliminates the daf-c and clk-1-mediated extension of adult lifespan. ctl-1 encodes an unusual cytosolic catalase; a second gene, ctl-2, encodes a peroxisomal catalase. ctl-1 messenger RNA is increased in dauer larvae and adults with the daf-c mutations. We suggest that the ctl-1 catalase is needed during periods of starvation, as in the dauer larva, and that its misexpression in daf-c and clk-1 adults extends lifespan. Cytosolic catalase may have evolved to protect nematodes from oxidative damage produced during prolonged dormancy before reproductive maturity, or it may represent a general mechanism for permitting organisms to cope with the metabolic changes that accompany starvation.
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PMID:A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants. 1261 Jun 32

Aging and limited life span are fundamental biological phenomena observed in a variety of species [1]. Approximately 55 genes have been identified that can extend longevity when altered in Caenorhabditis elegans [2-5]. These genes include an insulin-like receptor (daf-2) and a phosphatidylinositol 3-OH kinase (age-1) regulating a forkhead transcription factor (daf-16) [6, 7], as well as genes mediating metabolic throughput [8], sensory perception [9], and reproduction [10]. Moreover, these mutant alleles both extend life span and increase resistance to ultraviolet (UV) radiation [11], heat [12], and oxidative stress [13-15], though the stress resistance of clk-1 is controversial. With the exception of old-1 and perhaps some other genes [16-19], all of the life-extension alleles are hypomorphic or nullomorphic. Here, we show that the OLD-1 transmembrane tyrosine kinase (formerly TKR-1; [16, 20]) is expressed in a variety of tissues, is stress inducible, and is a positive regulator of longevity and stress resistance. The transcription of old-1 is upregulated in long-lived age-1 and daf-2 mutants and is upregulated in response to heat, UV light, and starvation. Both RT-PCR and analysis of an OLD-1::GFP tag suggest that old-1 expression is dependent on daf-16. Importantly, old-1 is required for the life extension of age-1 and daf-2 mutants. This study reveals a new system for specifying longevity and stress resistance and suggests possible mechanisms for mediating life extension by dietary restriction and hormesis.
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PMID:The OLD-1 positive regulator of longevity and stress resistance is under DAF-16 regulation in Caenorhabditis elegans. 1159 19

Mutations in the insulin/IGF-1 neuroendocrine pathway extend lifespan and affect development, metabolism, and other biological processes in Caenorhabditis elegans and in other species. In addition, they may play a role in learning and memory. Investigation of the insulin/IGF-1 pathway may provide clues for the prevention of age-related declines in cognitive functions. Here, we examined the effects of the life-extending (Age) mutations, such as the age-1 (phosphatidylinositol 3-OH kinase) and daf-2 (insulin/IGF-1 receptor) mutations, on associative learning behavior called isothermal tracking. This thermotaxis learning behavior associates paired stimuli, temperature, and food. The age-1 mutation delayed the age-related decline of isothermal tracking, resulting in a 210% extension of the period that ensures it. The effect is dramatic compared with the extension of other physiological health spans. In addition, young adults of various Age mutants (age-1, daf-2, clk-1, and eat-2) showed increased consistency of temperature-food association, which may be caused by a common feature of the mutants, such as the secondary effects of life extension (i.e., enhanced maintenance of neural mechanisms). The age-1 and daf-2 mutants but not the other Age mutants showed an increase in temperature-starvation association through a different mechanism. Increased temperature-food association of the daf-2 mutant was dependent on neuronal Ca2+-sensor ncs-1, which modulates isothermal tracking in the AIY interneuron. Interestingly, mutations in the daf-7 TGFbeta gene, which functions in parallel to the insulin/IGF-1 pathway, caused deficits in acquisition of temperature-food and temperature-starvation association. This study highlights roles of the Age mutations in modulation of certain behavioral plasticity.
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PMID:Aging-dependent and -independent modulation of associative learning behavior by insulin/insulin-like growth factor-1 signal in Caenorhabditis elegans. 1630 2