Honda S et al. (1997) International C. elegans Meeting "Oxidative Stress and Life Span"

Honda Y, Honda S

[International C. elegans Meeting, 1997]

In order to clarify the relationship between oxidative stress and life span, the susceptibility to oxidative stress has been measured in various life-extension mutants and their double mutants. We have measured the adult life span of the daf-2 mutant under hyperoxia which is considered to exert oxidative stress by generating active oxygen species. Hyperoxia reduced N2 life span. By contrast, the effect of hyperoxia on the life span in the daf-2 mutant was less than that in N2 Some of the life-extension mutants (daf-2 and age-1) were more resistant to the lethal effect of acute oxidative stress than N2. On the other hand, the other life-extension mutant clk-1 and the other daf mutants which do not show life extension were not resistant to oxidative stress. To understand genetic pathway conferring oxidative stress resistance, we have measured oxidative stress resistance in various double mutants. The double mutants of daf-2 and age-1 with daf-16 or daf-18 showed normal resistance to oxidative stress, except that daf-18; age-1 showed intermediate resistance between age-1 and daf-18. These oxidative stress resistance were associated with increase in gene expression of antioxidant defense enzymes. These results indicate that one of the genetic pathways conferring longevity also specify oxidative-stress resistance.

Honda S et al. (1987) International C. elegans Meeting "transcription of selected genes during development."

Honda S, Abruzzeze RV, Epstein HF

[International C. elegans Meeting, 1987]

Honda S et al. (1995) International C. elegans Meeting "Responses to oxygen in the daf-2 and daf-12 mutants"

Honda S, Honda Y

[International C. elegans Meeting, 1995]

Oxygen has been postulated to play a role in the aging processes (S. Honda et al., 48 B57 93), although it is not yet known how oxygen is involved. The mutants of daf-2 (C. Kenyon et al., Nature 366 461 93) and daf-2;daf-12 (P. L. Larsen & D. L. Riddle WBG 13 40 94) are known to have a longer lifespan than that of the wild type. We hypothesize that the daf-2 and daf-12 genes would be involved in the regulational system relating to active oxygen species so that their muta- tions would affect the lifespan by reducing peroxida- tion-induced damage. (1) Although hyperoxia or hypoxia hardly affect egg laying in the wild type, hyperoxia inhibited egg laying in the daf-2 mutant. On the other hand, hypoxia stimulated egg laying in the daf-2 mutant. While the daf-2;daf-12 mutant did not lay eggs when it was shifted to a nonpermissive temperature after the L3 stage, hypoxia partly rescued the egg-laying suppression in the daf-2; daf-12 mutant. (2) Hyperoxia strongly reduced the SDS-resistant fraction (Dauer larvae) in the daf-2 mutant. (3) Hyperoxia induces the supernumerary nuclear division in the intestine (S. Honda & G. Nelson in prep.). This induction was suppressed in the daf-2 mutant and stimulated in the daf-12 mutant. These results suggest that these mutants affect the lifespan by controlling the oxygen-relating regula- tional system.

Honda S et al. (1991) International C. elegans Meeting "Oxygen-sensitive mutants of C.elegans and aging"

Suzuki K, Matsuo M, Ishii N, Honda S

[International C. elegans Meeting, 1991]

The effects of oxygen are thought to be relevant to the aging process. Using the wild type and oxygen-sensitive mutants of C.elegans, relationships between their life spans and oxygen concentration were investigated. Several oxygen-sensitive mutants were isolated and identified: i.e., oxy-l, oxy-2, oxy-3, dpy-18, rad-8, mev-l, and mev-3. The mev-l mutant was found to have less superoxide dismutase activity than the wild type. The mean and maximum life spans of the mev-l mutant were shorter under an air atmosphere than those of the wild type. The mean and maximum life spans of those animals shortened with increasing atmospheric-oxygen concentration. In particular, the mean and maximum life spans of the mev-l mutant changed in sharp response to oxygen concentration. A partial revertant of the mev-l mutant was obtained by EMS treatment. When compared with the mev-l mutant, the revertant became less sensitive to high concentrations of oxygen and became long-lived under an air atmosphere. These results suggest that oxygen is one of life span determinants of C. elegans.

Honda S et al. (1989) International C. elegans Meeting "an oxygen-sensitive mutant of C elegans and aging."

Ishii N, Honda S, Suzuki K, Matsuo M

[International C. elegans Meeting, 1989]

Honda S et al. (1993) International C. elegans Meeting "Effects of radiation and oxidative stress on development and morpohology of intestinal cells."

Honda S, Schubert WW, Nelson GA

[International C. elegans Meeting, 1993]

Honda S et al. (1985) International C. elegans Meeting "runoff transcription in isolated nuclei and its application in studying gene activity in mutants."

Honda S, Epstein HF

[International C. elegans Meeting, 1985]

Yoko Honda et al. (2005) International Worm Meeting "Effects of the gene disruption of SOD on stress resistance, development and lifespan in Caenorhabditis elegans"

Shuji Honda, Yoko Honda

[International Worm Meeting, 2005]

Insulin/IGF-I signaling controls stress resistance and development as well as aging in C. elegans. We found that the expression of sod-3, one of two Mn superoxide dismutase (SOD) isoform genes (sod-2 and sod-3), was much higher in insulin/IGF-I receptor (DAF-2) mutants (1) and phosphatidyl inositol 3 kinase (AGE-1) mutants (2) than in N2. To elucidate the function of MnSODs in the control by insulin/IGF-I signaling, the effects of MnSOD gene deletions in the background of daf-2 mutants on stress resistance, lifespan and dauer formation were examined. The severity of oxidative-stress sensitivity was as follows: N2 < sod-3 < sod-2 < sod-2; sod-3. However, the deletion of sod-2 or sod-3 gene does not affect oxidative-stress resistance in daf-2 mutant, although oxidative-stress resistance was totally abrogated in the triple mutant: sod-2; daf-2; sod-3. The lifespan of sod-2; daf-2 double mutant and sod-2; daf-2; sod-3 triple mutant were longer than N2 but were slightly shorter than that of daf-2, while that of daf-2; sod-3 double mutant was longer than that of daf-2. These findings indicated that oxidative-stress resistance did not correlate with lifespan extension in daf-2 mutants upon MnSOD disruption. The effects of the sod deletions on dauer formation in daf-2 were examined. The relationship between reactive oxygen species and development and aging will be discussed.(1) Honda Y, Honda S. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J. 13:1385-1393. 1999(2) Honda Y, Honda S. Life span extensions associated with upregulation of gene expression of antioxidant enzymes in Caenorhabditis elegans; Studies of mutation in the age-1, PI3 kinase homologue and short-term exposure to hyperoxia. J. Amer. Aging Assoc. 24: 179-186. 2001

Yoko Honda et al. (2006) East Asia C. elegans Meeting "Study of space-flight effect on the aging of C. elegans in the International C. elegans Experiment (ICE)-First."

Akira Higashibata, Noriaki Ishioka, Masashi Tanaka, Shuji Honda, Yoko Honda

[East Asia C. elegans Meeting, 2006]

As exposures to the space environment become longer, information regarding the effects on biological aging will become important. We have not yet fully clarified aging processes in space environments. The aging process and lifespan are affected by various kinds of environmental factors including oxygen concentration<SUP>1)</SUP>, temperature and radiation. The aging phenomena that we usually see occur under certain conditions on the ground. Space environments differ from ground environments especially with regard to the radiation spectrum and gravity. We participated in the International Caenorhabditis elegans Experiment (ICE)-First that examined the effects of a 10-day space flight on the nematode C. elegans. C. elegans has frequently been used for study of aging because of its short lifespan and powerful genetic system. Recently, Morley et al. reported that Huntington's-like polyglutamine (polyQ)-repeat proteins expressed in the muscle of C. elegans form aggregates as the animals age, and that this aggregation is delayed in long-lived mutants<SUP>2)</SUP>. We measured the polyQ aggregates in these nematodes after space flight as an aging marker. We also examined the effects of space flight on the gene expression by DNA microarray analysis and real time PCR. The expression of several genes specifically for nervous systems was suppressed in space-flown animals, suggesting inactivation of nervous functions in space. The relationship between aging and changes in the gene expression in space will be discussed. 1) Honda S et al. Oxygen-dependent perturbation of life span and aging rate in the nematode. J Gerontol. 48:B57-61, 1993. 2) James F et al. The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA, 99: 10417-10422, 2002.

Yoko Honda et al. (2007) International Worm Meeting "Study of space-flight effect on the aging of C. elegans in the International C. elegans Experiment (ICE)-First."

Yoko Honda, Masashi Tanaka, Noriaki Ishioka, Akira Higashibata, Shuji Honda

[International Worm Meeting, 2007]

. Yoko Honda1, Akira Higashibata2, Noriaki Ishioka2, Masashi Tanaka1, Shuji Honda1. 1) Genomics for Longevity & Health, Tokyo Metropolitan Institute of Gerontology(TMIG), Tokyo, Japan; 2) Japan Aerospace Exploration Agency(JAXA), Tsukuba, Japan. As exposures to the space environment become longer, information regarding the effects on biological aging will become important. We have not yet fully clarified aging processes in space environments. The aging process and lifespan are affected by various kinds of environmental factors including oxygen concentration (1), temperature and radiation. The aging phenomena that we usually see occur under certain conditions on the ground. Space environments differ from ground environments especially with regard to the radiation spectrum and gravity. We participated in the International Caenorhabditis elegans Experiment (ICE)-First that examined the effects of a 10-day space flight on the nematode C. elegans. C. elegans has frequently been used for study of aging because of its short lifespan and powerful genetic system. Recently, Morley et al. reported that Huntington''s-like polyglutamine (polyQ)-repeat proteins expressed in the muscle of C. elegans form aggregates as the animals age, and that this aggregation is delayed in long-lived mutants (2). We measured the polyQ aggregates in these nematodes after space flight as an aging marker. We also examined the effects of space flight on the gene expression by DNA microarray analysis and real time PCR. The expression of more than ten genes specifically for nervous systems was suppressed in space-flown animals, suggesting inactivation of nervous functions in space. Next, effects of inactivation of these genes on lifespan were tested by RNAi in the laboratory. 1) Honda S et al.Oxygen-dependent perturbation of life span and aging rate in the nematode. J Gerontol. 48:B57-61. 1993 2) James F et al. The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA, 99: 10417-10422. 2002.