Disease relevance of age-1

• The role of genetically determined aging pathways in the progression of age-dependent polyQ-mediated aggregation and cellular toxicity was tested by expressing Q82 in the background of age-1 mutant animals that exhibit an extended lifespan [1].
• In addition, control experiments to determine the amount of RNA contributed by E. coli bacteria (present in the nematode culture medium as a food source) suggest that the age-1 mutant strain has a lower bacterial infection rate, which may contribute to the increased life span of this strain [2].
• We have shown that mutations in the age-1, and/or age-2 genes of C. elegans, that normally enhance life expectancy, can also increase resistance to killing by the bacterial pathogens Pseudomonas aeruginosa, Salmonella enterica var [3].

High impact information on age-1

• In Caenorhabditis elegans, mutations that reduce the activity of an insulin-like receptor (daf-2) or a phosphatidylinositol-3-OH kinase (age-1) favour entry into the dauer state during larval development and extend lifespan in adults [4].
• The gene age-1 is required for non-dauer development and normal senescence. age-1 encodes a homologue of mammalian phosphatidylinositol-3-OH kinase (PI(3)K) catalytic subunits [5].
• Mutant males also show a lengthening of life and a slowing of the rate of acceleration of mortality, although age-1 mutant males still have significantly shorter life-spans than do hermaphrodites of the same genotype [6].
• The Itt phenotype cosegregates with age-1 [7].
• Its position on the physical map of the genome was in the region to which the age-1 gene has been genetically mapped, but it is unlikely that a mutation at the SOD locus confers the Age phenotype [8].

Biological context of age-1

• 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 [9].
• Mutations in either the daf-2 insulin receptor-like (IRL) gene or the age-1 encoded PI3'K catalytic subunit homolog cause constitutive dauer formation and also affect the life span, brood size, and metabolism of nondauer animals [10].
• Both daf-2 and age-1 act at a similar point in the genetic epistasis pathway for dauer arrest and longevity and regulate the activity of the daf-16 gene [11].
• The age-1 strain TJ401 displayed hyperresistance to oxidative stress relative to its parental strain [8].
• Two recent papers report that daf-2 encodes a member of the insulin-receptor family and that age-1 encodes a PI3 kinase subunit, a second-messenger producing enzyme known to act downstream of the mammalian insulin receptor [12].

Anatomical context of age-1

• We conclude that increased expression of proteins that protect eukaryotic cells against environmental stress and/or repair stress-induced molecular damage confers hypertonic stress resistance in C. elegans daf-2/age-1 mutants [13].

Associations of age-1 with chemical compounds

• We found that daily short-term exposure (3 h) to hyperoxia further extended the life span of age-1, a phenomenon known as an adaptive response. age-1 also showed resistance to paraquat and heat [14].
• Mutations in the daf-2 insulin receptor-like gene or the downstream age-1 phosphoinositide 3-kinase gene extend adult life-span by two- to threefold [15].
• However, age-1 animals unable to synthesize trehalose survive poorly under hypertonic conditions [13].
• Here, we quantitatively analyzed total RNA, poly(A)+ RNA, and ribosomal RNA as a function of chronological age in two different strains (TJ1060 and TJ1061) having wild-type life spans and in a long-lived age-1 mutant strain (TJ1062) [2].

Other interactions of age-1

• 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] [16].
• Each of three well-studied mutants (age-1, clk-1, and spe-26) alters age-specific mortality rates in a fashion unique to itself [17].
• Mutations in daf-16 cause a dauer-defective phenotype and are epistatic to the diapause arrest and life span extension phenotypes of daf-2 and age-1 mutants [11].
• MT1 mRNA levels were significantly (P<0.05) higher in daf-2 mutants compared to age-1 mutants and wild-type C. elegans under basal conditions [18].
• Genetic analysis of the roles of daf-28 and age-1 in regulating Caenorhabditis elegans dauer formation [19].

References