Tullet, Jennifer et al. (2015) International Worm Meeting "The SKN-1/Nrf2 transcription factor protects against oxidative damage and promotes longevity in C. elegans by distinct mechanisms."

Gems, David, Au, Catherine, Clarke, Emily, Tullet, Jennifer, Young, Adelaide

[International Worm Meeting, 2015]

In C. elegans the skn-1 gene encodes a transcription factor that resembles mammalian Nrf2 and activates the detoxification response. skn-1 promotes resistance to oxidative stress and also protects against ageing, and it has been suggested that the former causes that latter - consistent with the theory that oxidative damage causes ageing. While long-lived strains are often stress resistant, they are not always. Moreover, a number of studies suggest that molecular damage may not in fact be the cause of ageing, particularly in C. elegans. Here we present work suggesting that effects of SKN-1 on stress resistance and longevity can be dissociated. We focus on the role of SKN-1 downstream of DAF-16/FoxO, another key transcription factor that controls growth, metabolism and ageing. Over-expression of DAF-16 promotes stress resistance and can increase longevity. Recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, many of which encode other regulatory proteins. We show that one of these targets is skn-1 and that this transcription factor is required for the stress resistance caused by over-expressing DAF-16. However skn-1 is not required for DAF-16-mediated lifespan extension. Moreover, knock-down of skn-1 expression can increase molecular damage levels without decreasing lifespan. These findings suggest that SKN-1 mediates lifespan extension by a means other than protection against damage, and elucidate the gene-regulatory network centered on DAF-16. We also present evidence that the mechanisms of life extension by daf-2 mutation or DAF-16 over-expression are mechanistically different.

Hogger CH et al. (1977) Nematologica "Surface scanning observations of changes in C. briggsae during aging."

Estey RH, Zuckerman BM, Hogger CH, Kisiel MJ

[Nematologica, 1977]

SEM observations of adult Caenorhabditis briggsae females showed differences between young and old nematodes. In young nematodes the cuticle was generally smooth, whereas in old ones it was wrinkled. Deirids were located at the level of the excretory pore in the lateral field. They were distinct in young nematodes but indistinct in old ones. The oral opening was formed by six lips, which were closed in old nematodes and open in young ones. The vulva possessed two semi-circular lips and was bordered by two lateral flaps. These lips were smooth in young specimens and wrinkled in old ones. Cryofractures of old nematodes showed cavities in the intestinal epithelium corresponding to areas in which age pigment granules normally occur. No such cavities were seen in young nematodes.

Sutphin GL (2019) Elife "A new defense in the battle of the sexes."

Sutphin GL

[Elife, 2019]

Young <i>Caenorhabditis elegans</i> hermaphrodites use their own sperm to protect against the negative consequences of mating.

Zuckerman BM et al. (1972) Journal of Nematology "Specific gravity increase of C. briggsae with age."

Kisiel MJ, Zuckerman BM, Nelson B

[Journal of Nematology, 1972]

The specific gravity of old Caenorhabditis briggsae was shown to be greater than that of young nematodes. The possible explanations for this age-associated change are discussed.

Yoon KH et al. (2020) Sci Rep "Consumption of Oleic Acid During Matriphagy in Free-Living Nematodes Alleviates the Toxic Effects of the Bacterial Metabolite Violacein."

Choi SY, Yoon KH, Lee TY, Choi YJ, Il Lee J, Mitchell RJ, Moon JH

[Sci Rep, 2020]

Maternal behaviors benefit the survival of young, contributing directly to the mother's reproductive fitness. An extreme form of this is seen in matriphagy, when a mother performs the ultimate sacrifice and offers her body as a meal for her young. Whether matriphagy offers only a single energy-rich meal or another possible benefit to the young is unknown. Here, we characterized the toxicity of a bacterial secondary metabolite, namely, violacein, in Caenorhabditis elegans and found it is not only toxic towards adults, but also arrests growth and development of C. elegans larvae. To counteract this, C. elegans resorted to matriphagy, with the mothers holding their eggs within their bodies and hatching the young larvae internally, which eventually led to the mothers' death. This violacein-induced matriphagy alleviated some of the toxic effects of violacein, allowing a portion of the internally-hatched young to bypass developmental arrest. Using genetic and pharmacological experiments, we found the consumption of oleate, a monounsaturated fatty acid produced by the mother, during matriphagy is partially responsible. As such, our study provides experimental evidence of why such a drastic and peculiar maternal behavior may have arisen in nematode natural habitats.

Anderson GL (1982) Can J Zool "Superoxide dismutase activity in dauerlarvae of C. elegans (Nematoda: Rhabditidae)."

Anderson GL

[Can J Zool, 1982]

Dauerlarvae are reportedly adapted to withstand adverse environmental conditions. Current knowledge of the mechanisms underlying the unique characteristics of dauerlarvae is limited. This study characterizes superoxide dismutase (SODase) activity in several developmental stages of Caenorhabditis elegans (originally described by E. Maupas in 1900). Extracts of dauerlarvae have 17.1 units SODase per milligram protein, as compared with 4.3 and 3.8 units per milligram for obligate larvae and young adults, respectively. Since oxygen consumption in dauerlarvae is lower than that of young adults, the ratio of SODase to oxygen consumption is markedly higher in dauerlarvae than in young adults. The elevated SODase might contribute to an increased resistance to a variety of environmental stresses, including radiation. Furthermore, the elevation of this activity relative to metabolic rate could account for the long life-span of dauerlarvae.

Ma F et al. (2023) Cell Genom "Young duplicate genes show developmental stage- and cell type-specific expression and function in Caenorhabditis elegans."

Ma F, Zheng C, Lau CY

[Cell Genom, 2023]

Gene duplication produces the material that fuels evolutionary innovation. The "out-of-testis" hypothesis suggests that sperm competition creates selective pressure encouraging the emergence of new genes in male germline, but the somatic expression and function of the newly evolved genes are not well understood. We systematically mapped the expression of young duplicate genes throughout development in Caenorhabditis elegans using both whole-organism and single-cell transcriptomic data. Based on the expression dynamics across developmental stages, young duplicate genes fall into three clusters that are preferentially expressed in early embryos, mid-stage embryos, and late-stage larvae. Early embryonic genes are involved in protein degradation and develop essentiality comparable to the genomic average. In mid-to-late embryos and L4-stage larvae, young genes are enriched in intestine, epidermal cells, coelomocytes, and amphid chemosensory neurons. Their molecular functions and inducible expression indicate potential roles in innate immune response and chemosensory perceptions, which may contribute to adaptation outside of the sperm.

Wu D et al. (2012) Exp Gerontol "Fertility/longevity trade-offs under limiting-male conditions in mating populations of Caenorhabditis elegans."

Wu D, Tedesco PM, Johnson TE, Phillips PC

[Exp Gerontol, 2012]

Evolutionary theories of aging suggest that trade-offs between longevity and fitness should be found under certain conditions. In C. elegans, there is little evidence for the existence of such trade-offs. We asked if fertility/longevity trade-offs exist in populations of randomly mating males and hermaphrodites. We set up a large population of young males and 5-day-old hermaphrodites that were no longer self-fertile. We then allowed them to mate for one day with an equal number young males and then separated hermaphrodites to individual plates and determined daily fertility of individual hermaphrodites. There was a significant negative relationship between late-life fertility and individual longevity.

Meng J et al. (2016) Redox Biol "The decay of Redox-stress Response Capacity is a substantive characteristic of aging: Revising the redox theory of aging."

Li X, Zhang Y, Lv Z, Meng J, Li Y, Qiao X, Chen C

[Redox Biol, 2016]

Aging is tightly associated with redox events. The free radical theory of aging indicates that redox imbalance may be an important factor in the aging process. Most studies about redox and aging focused on the static status of oxidative stress levels, there has been little research investigating differential responses to redox challenge during aging. In this study, we used Caenorhabditis elegans and human fibroblasts as models to compare differential responses to oxidative stress challenge in young and old individuals. In response to paraquat stress, young individuals generated more ROS and activated signaling pathways including p-ERK, p-AKT and p-AMPK/. After the initial response, young individuals then promoted NRF2 translocation and induced additional antioxidant enzymes and higher expression of phase II enzymes, including SOD, CAT, GPX, HO-1, GSTP-1and others, to maintain redox homeostasis. Moreover, young individuals also demonstrated a better ability to degrade damaged proteins by up-regulating the expression of chaperones and improving proteasome activity. Based on these data, we propose a new concept &quot;Redox-stress Response Capacity (RRC)&quot;, which suggests cells or organisms are capable of generating dynamic redox responses to activate cellular signaling and maintain cellular homeostasis. The decay of RRC is the substantive characteristic of aging, which gives a new understand of the redox theory of aging.

Specht S et al. (2009) Parasitol Res "Criteria for the differentiation between young and old Onchocerca volvulus filariae."

Buttner M, Specht S, Buttner DW, Brattig N

[Parasitol Res, 2009]

Drugs exist that show long-lasting inhibition of embryogenesis and microfilaria production or macrofilaricidal activity against Onchocerca volvulus. Therefore, the patients have to be followed-up for several years. Clinical drug trials have to be performed in areas with ongoing transmission to assess the efficacy on younger worms. In addition, future vaccine trials may also require demonstrating efficacy against establishment of new worms. For the evaluation of the efficacy, it is necessary to differentiate between older worms, which were exposed to the drug, and younger worms newly acquired after drug treatment or vaccination. Here, we describe criteria for the differentiation between young and old filariae based on histological studies of worms with a known age from travellers, or from children, or patients living in areas with interrupted transmission in Burkina Faso, Ghana or Uganda. Older worms were larger and presented degenerated tissues. Gomori's iron stain showed that the worms accumulated more iron with increasing age, first in the gut and later in other organs. Using an antibody against O. volvulus lysosomal aspartic protease, the gut of young worms was stained only weakly; whereas, it was stronger labelled in older worms, accompanied by additional staining of hypodermis and epithelia. Using morphological and immunohistological criteria, it was possible to differentiate young (1-3 years old) from older females and to identify young males.