Science AI Journal
Biochemistry, Genetics and Molecular Biology · Research topic

Open research questions in Genetics, Aging, and Longevity in Model Organisms

45 unresolved questions extracted from the limitations and future-work sections of 236 Genetics, Aging, and Longevity in Model Organisms papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • While FASN has been extensively studied in cultured cells, particularly for its oncogenic role, its functions in the germline and early embryonic development remain elusive.

    Loss of <i>ptr-6</i> restores eggshell integrity and embryonic viability in <i>C. elegans</i> fatty acid synthase mutants · 2026 · DOI

  • Whether or not different concentrations of V14™ could also impact lifespan remains to be seen but the hypothesis remains, that interventions to improve health in ageing humans, will have a sig- nificant effect on quality of life and may also extend lifespan by delaying the onset of age-related diseases (Kaeberlein et al.

    A multi-ingredient food supplement slows age-dependent decline of mobility and influences gene expression in C. elegans · 2026 · DOI

  • However, the combined metabolomics and proteomics profile associated with the delayed CMD onset observed in such long-lived family members is not understood yet.

    Multi-omics integration identifies metabolic and inflammatory pathways underlying familial longevity · 2026 · DOI

  • “Leader cells” remodel ECM, sense guidance cues, reorganize their cytoskeleton, and coordinate follower cells, but the molecular programs enabling these functions remain unclear.

    Stage-specific transcriptomics of a leader cell reveals cell machineries driving collective invasion · 2026 · DOI

  • Despite our efforts, our research still presents several limitations. The reported Pearson correlations between anatomical and optimized synaptic weights should not be interpreted as evidence that all individual synaptic weights are reproduced with equal fidelity. Rather, these values summarize broad correspondence between the optimized and anatomical synaptic weight structures under connectome constraints. Because the model uses a fixed topology and simplified neuronal dynamics, the optimized parameters should be interpreted as model-dependent, task-specific effective synaptic weights rather than as uniquely identifiable biological synaptic strengths. In addition, the existence of multiple successful machine-learning trajectories ARTICLE IN PRESS ARTICLE IN PRESS ACCEPTED MANUSCRIPT indicates degeneracy in the solution space. It remains unclear whether this degeneracy arises from flexibility of the model, incomplete physiological constraints, or natural biological variability of the connectome across individuals [5,7]. In particular, this degeneracy may reflect either biological robustness or redundancy in the C. elegans locomotor circuit or underdetermination of the present model due to limited physiological and behavioral constraints. We therefore do not interpret any single optimized trajectory as a unique biological solution. Instead, we regard features that recur across converged trajectories, such as broad correspondence with anatomical synaptic weights, appropriate locomotor kinematics, and repeated identification of particular neurons in ablation-based analyses, as more informative than any individual parameter set. Testing spiking neuron formulations remains an important future direction. Second, experimental findings indicated that trp-1,2 mutation did not eliminate the oscillation of SMDD neuron activity, but merely altered its phase. However, trp-1,2 mutation completely silenced the SMDD oscillation in the CANN model. A further limitation is that, although the model reproduced the qualitative locomotor bias associated with the simulated trp- 1,2 perturbation, the present analysis does not yet fully explain the internal dynamical mechanism by which removal of proprioceptive input to SMDD leads to circular locomotion. Third, because the forward- and backwardlocomotion command artificially set membrane potentials of commandneurons to constant values of 0 or 1, the activity of command-neurons does ARTICLE IN PRESS ARTICLE IN PRESS ACCEPTED MANUSCRIPT not vary continuously, potentially diverging from the actual neuronal activity in C. elegans. Accordingly, command interneurons were excluded from the type I/II necessity analyses.

    Optimization of connectome weights for a neural network model generating both forward and backward locomotion in C. elegans · 2026 · DOI

  • In conclusion, genetic screens in C. elegans have proven invaluable for uncovering new immune regulators and functions, ranging from evolutionarily conserved signalling pathways to speciesspecific innovations that may still have parallels in other systems. The diversity of studies spans a wide range of pathogens including viruses, bacteria, microsporidia, and oomycetes and has been facilitated by both controlled infection assays in lab conditions and the establishment of immune reporter strains. Importantly, genetic screens have identified regulators that act in different tissues or across to coordinate systemic immune responses. Thus, C. elegans represents a powerful whole-animal model to provide insights into how local and distal signals are integrated to orchestrate organism-wide immunity. tissues With regard to immune programmes, the comparison between the regulation of IPR and ORR highlights some emerging themes (Fig. 1). For example, there is evidence for co-regulation of key immune factors, such as the clec receptor pairs sharing the same promoter or the pals-22/25 module being part of the same operon. Furthermore, relevant gene families for immune programmes have been shown to include members that transcriptionally respond to infection, as well as other members that do not respond, yet play a key regulatory role e.g., the pals-22/25 regulation of other responding pals genes such as pals-5.

    Worming out defence strategies: mechanisms of immunity through the lens of genetic screens in C. elegans · 2026 · DOI

  • Immunostaining of fixed sperm with anti-MO 1CB4 monoclonal antibodies was restricted to conventional confocal microscopy at 555 nm; super-resolution imaging (STORM, PALM) of MO fusion pore architecture during acrosomal-like exocytosis in SPE-56-deficient males has not been performed.

    The intrinsically disordered protein SPE-56 is required for acrosomal-like exocytosis and fertility in Caenorhabditis elegans · 2026 · DOI

  • The quantification of spontaneous (premature) sperm activation in spe-56 mutants was categorized according to established benchmarks but the temporal progression of activation defects relative to SPE-56 intrinsic disorder domains (e.g., low-complexity regions, prion-like sequences) was not mapped.

    The intrinsically disordered protein SPE-56 is required for acrosomal-like exocytosis and fertility in Caenorhabditis elegans · 2026 · DOI

  • Live imaging of sperm activation in whole anesthetized worms using levamisole immobilization was performed only at 20°C; the effects of physiological temperature variation (37°C equivalent in C. elegans) on SPE-56-dependent MO fusion kinetics and pseudopod extension dynamics have not been investigated.

    The intrinsically disordered protein SPE-56 is required for acrosomal-like exocytosis and fertility in Caenorhabditis elegans · 2026 · DOI

  • The immunoprecipitation protocol using GFP-Trap agarose beads for identifying SPE-56 interacting proteins only recovered binding partners from whole sperm lysates; interaction dynamics during specific stages of acrosomal-like exocytosis (pre-activation, activation, post-fusion) remain uncharacterized.

    The intrinsically disordered protein SPE-56 is required for acrosomal-like exocytosis and fertility in Caenorhabditis elegans · 2026 · DOI

  • The FM 1-43 lipophilic membrane dye assay for detecting MO fusion pores in C. elegans spermatozoa has not been directly compared with alternative membrane fusion detection methods (e.g., patch-clamp electrophysiology, total internal reflection fluorescence microscopy) to validate the specificity and sensitivity of punctate fluorescence localization as a fusion indicator.

    The intrinsically disordered protein SPE-56 is required for acrosomal-like exocytosis and fertility in Caenorhabditis elegans · 2026 · DOI

  • The pumping behavior has long attracted significant research interest. As previously described, ADF neurons promote 5-HT production in response to bacterial food. In the downstream of ADF neurons, 5-HT inhibits RIC neurons by a chloride channel receptor MOD-1 in well-fed. OA from RIC neurons acts on two dierence receptors: SER-3/SER-6 in SIA neurons and SER- 6 in AWB neurons in starvation. A feedforward neural circuit is composed of three neurons: ADF, RIC and SIA with a simple mechanism, disinhibition, which lead to pumping increase (Liu et al., 2019). And an ADF → RIC → AWB → ADF neural feedback Although only four biogenic amines have been identified in C. elegans, these signaling molecules are capable of modulating a wide range of behavioral responses by diverse regulatory mechanisms. The complex spatial instructions of behavior originate from the interaction of dierent neurons in neural circuits mediated by multiple neurotransmitters and receptors, and are implemented through excitation, inhibition, feedforward, and feedback. These behavioral and metabolic regulations involve multi-level neurophysiological mechanisms of neural signaling.

    Deciphering the regulatory mechanism of neural behavioral decisions through biogenic amine-mediated modulation of neural circuits in Caenorhabditis elegans · 2026 · DOI

  • The quantification of RPL-34:mCherry expression employed manual marking of oocyte nuclei and distal germline regions with exclusion of nuclear signal, but the spatial heterogeneity of ribosomal protein distribution within individual oocytes across stages of oogenesis was not characterized. High-resolution volumetric imaging of germline development is needed to map ribosomal protein localization.

    Dietary restriction shapes intergenerational ribosome abundance and early growth of Caenorhabditis elegans offspring · 2026 · DOI

  • The polysome profiling analysis measured ribosome abundance via sucrose density gradient centrifugation, but the functional translational capacity (translation efficiency, ribosome elongation rates, or start codon selection) of maternal-inherited ribosomes versus de novo synthesized offspring ribosomes was not compared. Direct measurement of translation dynamics in early L1 larvae is required.

    Dietary restriction shapes intergenerational ribosome abundance and early growth of Caenorhabditis elegans offspring · 2026 · DOI

  • The study depleted ribosomal proteins using different Tir1 promoters (eft-3p:Tir1, sun-1p:Tir1, gld-1p:Tir1) with varying auxin concentrations (250–1000 μM), but the tissue-specific contribution of maternal somatic versus germline-localized ribosomes to offspring phenotypes was not quantitatively dissected. Comparative analysis of tissue-specific ribosomal protein depletion timing and dosage effects is needed.

    Dietary restriction shapes intergenerational ribosome abundance and early growth of Caenorhabditis elegans offspring · 2026 · DOI

  • Insulin/insulin-like signaling (IIS) via DAF-2 was ruled out as a mechanism for intergenerational ribosomal protein control, but other signaling pathways (TOR, AMPK, or nutrient-sensing pathways) were not systematically tested. Future work should directly interrogate alternative signaling cascades using auxin-inducible degradation of pathway-specific components in maternal germline or somatic tissues.

    Dietary restriction shapes intergenerational ribosome abundance and early growth of Caenorhabditis elegans offspring · 2026 · DOI

  • The weak inheritance of proteome changes across generations (R² = 0.037 between G0 and G1) indicates that most protein abundance alterations induced by dietary restriction in parents do not translate to offspring. The specific molecular mechanisms filtering which proteome changes are inherited versus which are reset in G1 L1 larvae remain uncharacterized.

    Dietary restriction shapes intergenerational ribosome abundance and early growth of Caenorhabditis elegans offspring · 2026 · DOI

  • The recovery kinetics of ribosomal proteins differ between auxin-induced depletion (RPS-26:AID:GFP) and maternal dietary restriction conditions, with faster recovery observed after auxin treatment than after DR. The molecular mechanisms driving these differential recovery rates during L1 larval development remain unexplored and require mechanistic investigation.

    Dietary restriction shapes intergenerational ribosome abundance and early growth of Caenorhabditis elegans offspring · 2026 · DOI

  • The goal of our survey was to assess modern thinking about the foundational issues in the biology of aging among experts who study this process. Despite its surprising findings of wide disagreement, we consider it a step forward. By simply identifying and spelling out the issue, it may be enough to inspire creative thinking, conceive new experimental approaches, and uncover new practical leads in the field of aging. 5 Cohen AA, et al. 2020. Lack of consensus on an aging biology paradigm? A global survey reveals an agreement to disagree, and the need for an interdisciplinary framework. Mech Ageing Dev. 191: 111316. 6 Gavrilov LA, Gavrilova NS. 2017. Is aging a disease? Biodemographers’ point of view. Adv Gerontol. 30:841–842. 7 Gladyshev TV, Gladyshev VN. 2016. A disease or not a disease? Aging as a pathology. Trends Mol Med. 22:995–996. 8 Rattan SI. 2014. Aging is not a disease: implications for interven- 9 tion. Aging Dis. 5:196–202. Bulterijs S, Hull RS, Bjork VC, Roy AG. 2015. It is time to classify biological aging as a disease. Front Genet. 6:205. 10 Cohen AA, Legault V, Fulop T. 2020. What if there’s no such thing as “aging”? Mech Ageing Dev. 192:111344. 11 Lemoine M. 2020. Defining aging. Biol Philos. 35:1–30. 12 Kirkwood TB. 1977. Evolution of ageing. Nature. 270:301–304. 13 Kirkwood TB, Austad SN. 2000. Why do we age? Nature.

    Disagreement on foundational principles of biological aging · 2024 · DOI

  • APOE epsilon4: the most prevalent yet understudied risk factor for Alzheimer’s disease.

    Functional analysis of late-onset Alzheimer’s disease risk genes in Caenorhabditis elegans identifies regulators of neuronal aging · 2026 · DOI

  • Future research should focus on further elucidating the molecular mechanisms involved and exploring the potential clinical applications of metformin in treating these bacterial infections.

    p38 MAPK and MDT-15 mediate SKN-1-dependent metformin-induced protection against mitis group streptococci in Caenorhabditis elegans · 2026 · DOI

  • However, how dauer entry, L1 arrest, and density-dependent signaling collectively influence long-term population dynamics remains poorly understood.

    Diapause and Developmental Arrest as Drivers of Population Resilience Through Stress · 2026 · DOI

  • ABSTRACT Ambient temperature is a primordial determinant of longevity across the animal kingdom, yet the molecular transducers that couple thermal cues to aging rates remain elusive.

    Sex‐Specific Regulation of the Turandot Gene Family Modulates Temperature‐Dependent Lifespan in <scp> <i>Drosophila melanogaster</i> </scp> · 2026 · DOI

  • Fatty acid biosynthesis is a central metabolic process required for membrane formation, organelle maintenance, and cellular proliferation, yet its broader relationship with stress responses and cellular aging remains incompletely understood.

    Fatty acid metabolic interactome atlas linked to cellular longevity · 2026 · DOI

  • Clove (Syzygium aromaticum) extracts promote longevity in several model systems, yet the underlying molecular mechanisms responsible for the pro-longevity remain poorly defined.

    Eugenol from Syzygium aromaticum enhances longevity and proteostasis in aged yeast · 2026 · DOI

Most-cited papers in Genetics, Aging, and Longevity in Model Organisms

Most recent work

Find a gap in your own Genetics, Aging, and Longevity in Model Organisms sub-topic

This page shows what the Genetics, Aging, and Longevity in Model Organisms literature already flags as unresolved. To narrow it to your specific question, run the guided finder — it searches the gap library on demand and checks candidates against 250M+ OpenAlex works.

Open the Research Gap Finder →

Related topics in Biochemistry, Genetics and Molecular Biology

Gut microbiota and health
289 open questions
Single-cell and spatial transcriptomics
185 open questions
dental development and anomalies
121 open questions
Mitochondrial Function and Pathology
110 open questions
Genetic Associations and Epidemiology
106 open questions
Human-Animal Interaction Studies
105 open questions
Genomics and Chromatin Dynamics
97 open questions
Inflammatory Bowel Disease
91 open questions
45 open questions have been extracted from the limitations and future-work passages of 236 Genetics, Aging, and Longevity in Model Organisms papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

Tools for your next paper

Gaps & Literature SearchFind open questions in any field — 120,000+ open gaps mined from our own library.Pre-CheckIs your paper ready? A Tier 1–5 acceptance probability in seconds.Journal FinderA ranked shortlist of target journals from a 17,500-venue index.Duplicate Publication CheckerCheck prior-publication & salami-slicing risk across 8 sources.Citation GeneratorFreeA DOI or title → APA, MLA, Vancouver, Chicago, BibTeX, RIS. No signup.Graphical Abstract MakerFreeTurn your findings into a colorblind-safe graphical abstract.

Compare the category — Honest roundups of the AI research tools, ours listed alongside the alternatives.

Command palette

Jump anywhere, run any action.