A study published today in the journal Science Advances, led by researchers at the longevity research non-profit Kallel in the United States, with collaborators including Dr Justin Gerlach of Peterhouse at the University of Cambridge, reports the first epigenomic investigation of a giant tortoise. The team identified 287 unique gene variants in Jonathan that appear to blunt the usual effects of ageing. These variants are not scattered randomly across his genome; they cluster around biological processes that gerontologists regard as the pillars of longevity: the repair of DNA damage, the control of inflammation, the regulation of insulin signalling, and the suppression of cancer. Together, they suggest that Jonathan’s extraordinary lifespan is not simply a matter of good fortune, but of an inherited molecular toolkit that keeps his cells functioning with remarkable fidelity.

The most striking finding concerns not the sequence of Jonathan’s genes, but the switches that govern them. The epigenome, the collection of chemical marks that turn genes on and off without altering the underlying DNA, is known to drift and degrade with age in most animals. These changes, which include shifts in DNA methylation patterns and other regulatory modifications, are widely considered a central driver of the ageing process, contributing to the gradual breakdown of tissue function that characterises older bodies. Yet when the researchers compared Jonathan’s epigenome with those of younger giant tortoises of the same species, they found that the switches controlling his DNA repair and metabolism genes were strikingly similar to those of his younger relatives. In effect, the regulatory architecture of his most critical maintenance genes has barely changed over almost two centuries of life.

“We found that the gene regulators involved in energy production and DNA repair have remained incredibly stable in Jonathan over almost two centuries,” said Dr Justin Gerlach, who has studied the ecology and conservation of giant tortoises for several decades but had never before examined their exceptional longevity. His observation points to a possibility that excites ageing researchers: that some long-lived species do not merely slow the passage of molecular time, but actively preserve the youthful regulation of the genes most essential to survival. If DNA repair pathways and metabolic control circuits remain properly calibrated in extreme old age, the cascade of damage that normally accumulates in ageing tissues may be held in check far longer than in short-lived animals.

The significance of the 287 protective variants becomes clearer when set against what is known about the biology of ageing. DNA damage accumulates throughout life from radiation, metabolic by-products and ordinary cellular wear, and unrepaired lesions drive mutations, cellular dysfunction and the activation of inflammatory pathways. Insulin and insulin-like signalling, meanwhile, is one of the most conserved regulators of lifespan across the animal kingdom, with reduced signalling consistently associated with extended longevity in laboratory models. Chronic low-grade inflammation, sometimes called inflammageing, underlies many of the diseases of old age, and cancer remains a persistent threat to any long-lived large animal, since more cells and more cell divisions create more opportunities for malignant transformation. Gene variants that reinforce DNA repair, temper insulin signalling, damp inflammation and suppress tumours would therefore be expected to act in concert, and that is precisely the pattern the study describes.

“Nature has already solved the puzzle of aging in remarkable ways, and Jonathan’s genome provides a blueprint for cellular resilience,” said Stephen Clark MD, PhD, founder of Kallel and senior author of the study. He added: “Our goal is to take these evolutionary insights and immediately translate them into practical, affordable treatments for everyday people. Aging is the greatest risk factor for nearly every chronic disease we face, and through the generosity of philanthropic partners, we can democratise access to longevity medicine.” The statement reflects a growing ambition within the longevity research field: to treat ageing itself, rather than its individual diseases, as the primary medical target, and to use the genomes of exceptionally long-lived species as guides for intervention in humans.

That ambition will require careful work. Identifying protective variants in a tortoise is a very different matter from reproducing their effects in human cells, let alone in patients. Gene variants that evolved over tens of millions of years in a slow-growing, cold-blooded reptile cannot simply be transplanted into a mammalian genome. But the epigenomic stability documented in Jonathan offers a more immediately tractable line of inquiry. Epigenetic marks are chemically modifiable, and a rapidly expanding toolkit of epigenetic therapies already exists. If researchers can determine precisely which regulatory marks keep Jonathan’s DNA repair and energy-production genes functioning as they did in his youth, they may be able to design interventions that restore similar regulation in ageing human tissues. The study, the first of its kind in any giant tortoise, provides the reference map from which such work can begin.

Jonathan himself remains very much a working animal rather than a museum specimen. He has spent nearly all of his 194 years in the grounds of Plantation House, grazing, resting and, famously, continuing to seek out mates well into extreme old age. Gerlach described the experience of working with him in unusually warm terms: “There are few creatures that could tell us more about ageing than the giant tortoises of the Galapagos and Seychelles islands. Working with a really old giant tortoise is such a privilege: you get a sense of the tortoise being your collaborator, not your study subject.” The remark captures something important about the study’s approach. Rather than treating Jonathan as an inert biological sample, the researchers framed the work as a collaboration with an animal whose body has already run the experiment that longevity science is trying to understand.

The giant tortoises of the Galapagos and Seychelles islands are, as the researchers note, the extraordinary last survivors of animals that once dominated the ecology of many of the world’s islands. Before human arrival, these slow-moving herbivores shaped vegetation, dispersed seeds and engineered landscapes across archipelagos from the Indian Ocean to the Pacific. Hunting, habitat destruction and introduced predators drove most island tortoise populations to extinction, and the survivors, including the Aldabra giant tortoise, now survive only in small, carefully protected populations. Jonathan’s longevity is thus not only a scientific curiosity but a reminder of what has been lost: lineages that may have carried similar longevity adaptations, extinguished before anyone could study them.

For now, Jonathan continues his slow rounds on St Helena, unaware that his blood and tissue samples have become some of the most closely examined biological material in the study of ageing. The study, published under the title reporting epigenetic insights into extreme longevity in the world’s oldest terrestrial animal, documents an experimental investigation of a single, irreplaceable individual, and its findings will need to be extended to other giant tortoises and related species to establish how general these mechanisms are. But the central message is already clear. Extreme lifespan is not an accident of circumstance; it is written in gene variants that protect the integrity of DNA, calm inflammation, restrain growth signals and defeat cancer, and it is maintained by an epigenome that refuses to drift out of calibration even after 194 years. In the shell of one very old tortoise, researchers have found a blueprint for cellular resilience that evolution spent millions of years perfecting, and that medicine is now eager to read.

Subject of Research: Epigenetic and genomic determinants of extreme longevity in the world's oldest land animal, an Aldabra giant tortoise

Article Title: Genetic analysis of the world's oldest land animal reveals secret of living 194 years

Article References: Genetic analysis of the world's oldest land animal reveals secret of living 194 years. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: Jonathan the tortoise, Aldabra giant tortoise, longevity, epigenome, DNA repair, ageing, gene variants, insulin signalling, cancer suppression, inflammation, St Helena, Science Advances

The biological foundation of this promise lies in duckweed’s extraordinary body plan. The family comprises five genera, Spirodela, Landoltia, Lemna, Wolffiella, and Wolffia, forming an evolutionary gradient from the rooted, structurally complex Spirodela to the rootless, millimeter-scale Wolffia, the smallest flowering plant known. This simplification is the product of reductive evolution: as ancestral land plants returned to water, they progressively shed roots, extensive vascular tissue, and woody structures. What remains is a leaf-like frond that reproduces clonally every one to three days, driven by meristematic activity in budding pouches at the frond base. That doubling rate, among the fastest of any vascular plant, translates directly into short production cycles and high volumetric yields in a biomanufacturing context.

Duckweeds also display remarkable developmental plasticity. Under nutrient starvation, crowding, or shortening days, many species switch from rapid vegetative growth to producing turions, dense dormant propagules packed with starch and lipids. Abscisic acid signaling initiates this program, cell division ceases, and storage compounds accumulate massively; breaking dormancy requires prolonged cold followed by warming and light, after which stored reserves fuel a new frond. Light quality offers another tuning dial: red versus blue light differentially steers biomass toward starch or protein, a lever that could let producers tailor output for biofuels, animal feed, or protein-rich products. Even the plant’s elemental composition shifts with its body plan, as rootless species show markedly lower tissue calcium and magnesium than their rooted relatives.

The genomic era has decoded the logic behind this minimalism. Chromosome-scale assemblies for Spirodela polyrhiza and Lemna minor, and a highly complete genome for Wolffia australiana, reveal a genus-by-genus contraction of gene families tied to lost structures, including lignocellulose biosynthesis, root development, and stomatal function. Yet reduction has been selective: Spirodela shows tandem expansions of disease-resistance genes and antimicrobial peptide genes, while an expanded flavonoid pathway supports ultraviolet protection at the water surface. Cytogenomic surveys of all 36 duckweed species have cataloged a complex history of whole-genome duplication, hybridization, and polyploidy, with triploid hybrids surprisingly common because the genetic pathways enforcing reproductive isolation appear weakened.

Perhaps the most consequential discovery for engineers is duckweed’s radically simplified epigenome. Spirodela polyrhiza has lost key components of the canonical RNA-directed DNA methylation pathway, resulting in very low levels of 24-nucleotide small interfering RNAs and drastically reduced cytosine methylation in gene bodies and repeats. Degenerated transposable elements are instead marked by alternative heterochromatin modifications such as H3K9me1 and H3K27me1, while only intact, potentially active elements retain a focused residual silencing mechanism. For biotechnologists, this matters enormously: reduced gene-silencing machinery lowers the risk that an introduced transgene will be epigenetically shut down, promising more predictable and stable expression of engineered traits than in conventional plant platforms.

Single-cell and metabolomic studies are filling in the remaining blueprint. Single-nucleus and single-cell RNA sequencing of Wolffia australiana resolved just four principal cell clusters, aquatic and aerial parenchyma plus epidermis, with remarkably few genes defining tissue specialization, confirming its status as a streamlined organism. A preliminary atlas of Lemna minuta highlighted mesophyll cells rich in elemental transport genes, consistent with the genus’s phytoremediation prowess. Meanwhile, a genome-wide association study of 137 Spirodela genotypes across 42 metabolites exposed a fundamental growth-metabolism trade-off: biomass correlates positively with free amino acids but negatively with specialized metabolites like flavonoids. The authors propose a two-phase cultivation strategy, first maximizing biomass, then triggering production pathways, mirroring approaches long used in microbial fermentation.

Genetic tooling has advanced just as dramatically. Early Agrobacterium-mediated protocols in Lemna gibba and Lemna minor relied on slow callus cultures, exemplified by an Indian isolate protocol that took 11 to 13 weeks and achieved only 3.8 percent transformation frequency. The Frond Transformation System changed the calculus by bypassing callus entirely, cutting stable line generation from eight or nine months to roughly three and extending compatibility to previously recalcitrant genotypes. CRISPR-Cas9 editing arrived in Lemna aequinoctialis in 2019 with a five-to-six-week cycle and a 14.3 percent biallelic mutant rate. More recently, a so-called duckweed dip method uses plasmid DNA wrapped around carbon nanotubes that plants absorb directly from their medium, and optimized platforms for Spirodela now report efficiencies exceeding 90 percent at every stage, completed in weeks. Endogenous promoters such as LpSUT2 from Landoltia punctata address another chronic problem, maintaining robust expression under stress conditions where the viral 35S promoter becomes methylated and silenced.

These tools are already yielding functional products. Duckweed has been engineered to express the Porcine Epidemic Diarrhea Virus spike protein, the conserved M2e peptide of avian influenza H5N1 at up to 1.96 percent of total soluble protein, and chicken interleukin-17B, which acted as an effective oral mucosal vaccine adjuvant in poultry. A duckweed-based edible vaccine recently conferred complete protection against avian infectious bronchitis virus by inducing robust mucosal and systemic immunity. Transient viral-vector systems achieve yields above one milligram per gram fresh weight within days. Compared with tobacco, the incumbent plant chassis, duckweed offers distinct advantages: it is naturally edible and free of alkaloid contaminants, its cell walls are low in lignin, simplifying extraction, and its obligate aquatic, rarely flowering habit provides built-in biological containment that mitigates transgene escape.

Traditional applications reinforce the platform’s credentials. Duckweed cover on irrigated paddies can almost entirely offset ammonia volatilization induced by water-saving irrigation, through a tripartite mechanism of physical gas blocking, direct ammonium uptake, and reduced water temperature. Replacing up to 15 percent of wheat and soybean meal in laying hen diets with Lemna minor maintained egg production while enhancing yolk color and showing hepatoprotective signs. Under combined nutrient limitation and elevated carbon dioxide, Landoltia punctata accumulated starch to more than 72 percent of dry weight at 10.4 grams per square meter per day, while mixotrophic bioreactor cultivation has reached growth rates of 152.3 grams per square meter per day, projecting yields near 50 tonnes of dry biomass per hectare annually. Duckweed systems also remove over 80 percent of chemical oxygen demand, over 90 percent of total phosphorus, and over half of total nitrogen from wastewater streams.

Significant hurdles remain before duckweed becomes an industrial workhorse. Large-scale cultivation must solve self-shading in dense mats, oxygen limitation under mixotrophic conditions, contamination in open water, and the fragility of fronds during harvesting, where mechanical skimming achieves 60 to 80 percent recovery and filtration exceeds 90 percent but clogs easily. Long-term transgene stability across hundreds of clonal generations lacks empirical data, and regulatory pathways for recombinant products from a novel aquatic host remain uncharted. The review’s authors call for integrated omics databases, universal genetic toolkits with standardized reporting, and scalable bioreactor designs to bridge the gap from proof of concept to production. If those pieces come together, the world’s smallest flowering plants may carry a disproportionate share of the sustainable manufacturing burden ahead.

Subject of Research: Duckweed biology and genetic engineering as a sustainable plant chassis for biotechnology

Article Title: Duckweeds: from fundamental biology to a sustainable plant chassis for biotechnology

Article References: Yin, G.-M., Yang, L., Li, S., & Zhang, Y. (2026). Duckweeds: from fundamental biology to a sustainable plant chassis for biotechnology. Advanced Biotechnology, 4(2), Article 16. https://doi.org/10.1007/s44307-026-00110-1

Image Credits: AI Generated

DOI: 10.1007/s44307-026-00110-1

Keywords: duckweed, Lemnaceae, plant chassis, molecular farming, CRISPR-Cas9, epigenome, phytoremediation, biopharmaceuticals, synthetic biology, genomics, starch production, sustainable biotechnology

The study, led by Sophie van Baalen, Thomas Verra and Michelle Habets of the Rathenau Instituut in the Netherlands, together with colleagues at Wageningen University and Erasmus MC, conducted nineteen semi-structured interviews with scientists working in academia and industry between September 2023 and January 2024. Fifteen of the respondents were academic researchers and four worked for commercial companies, with expertise spanning biomedical research, plant science and microbiology. Using snowball sampling and thematic analysis with Atlas.ti software, the team captured the views of researchers across ten European countries and one respondent from the United States, continuing recruitment until no new themes emerged from the transcripts.

The technical logic behind epigenetic editing explains much of its appeal. Unlike CRISPR-Cas9 gene editing, which slices both strands of the DNA double helix to alter the genetic sequence, epigenetic editing tools such as CRISPR-dCas9 and zinc finger proteins bind to specific DNA sequences without cutting them. Instead of changing the letters of the genetic code, they attach or remove chemical marks on the DNA and its associated proteins, dialing gene activity up or down. Because no DNA breaks are introduced, researchers assume the risk of genomic instability is dramatically reduced. Off-target effects, a persistent worry in gene editing, are viewed as less dangerous in the epigenetic version because misplaced edits do not coincide with strand cuts and may fade over time as the cell’s own machinery reverses the marks.

Respondents also described epigenetic editing as fundamentally more subtle than gene editing. Where gene editing acts like a binary switch, introducing or eliminating genetic functions outright, epigenetic editing was compared to a thermostat that fine-tunes the volume of gene expression. Because cells naturally modify their epigenome constantly as part of ordinary biology, scientists framed the technique as working with, rather than against, the cell’s native processes. Several researchers contrasted this precision favorably with epigenetic drugs, a class of therapeutics that targets epigenetic enzymes broadly and is notorious for lacking specificity. One interviewee emphasized the absence of the translocation problems and genetic instability that plague strand-cutting technologies, noting that unlike base editing, prime editing or conventional gene editing, epigenetic editing never cuts the DNA at all.

Yet the same scientists who endorsed this dominant vision simultaneously questioned its foundations, sometimes without being prompted. The reservations clustered around three scientific uncertainties: reversibility, heritability and complexity. On reversibility, researchers acknowledged that while a limited number of studies have shown epigenetic edits can be reversed or remain stable, it is currently impossible to predict whether an edit at a particular genomic location will persist or vanish, and for how long. This creates an awkward paradox, because the stability needed for durable medical treatments and agricultural applications is exactly what undermines the promised safety net of reversibility. As one respondent explained, scientists do not really know what makes some epigenetic modifications stick around for years while others disappear within days, and following patients long enough to find out would require decades-long cohort studies.

Heritability raised equally thorny questions. For epigenetic editing to work in medicine or agriculture, edits must survive cell division, a property called mitotic heritability, and respondents disagreed about whether they reliably do. The possibility of intergenerational and transgenerational inheritance troubled some biomedical researchers, who worried about unintended effects on the offspring of treated patients, while some plant scientists actually counted on epigenetic edits fading out over generations, reasoning that edited crops escaping into the wild would lose their modifications naturally. The third concern, complexity, struck at the heart of the technology’s predictability. Gene expression is governed by intertwined networks in which cause and effect are not linear; altering an epigenetic mark at one location can trigger cascades of unforeseen changes across hundreds of other genes, especially when the three-dimensional folding of DNA and crosstalk between cells enter the picture. One respondent noted that outside of genomic imprinting, they could not think of a single epigenetic network that is well enough characterized to guarantee a clear therapeutic output.

Despite these doubts, three distinct visions of the technology’s medical future emerged among respondents. The prevailing outlook was hopeful but modest: epigenetic editing could eventually treat cancers driven by epigenetic changes, boost the effectiveness of CAR-T immunotherapies, and address rare diseases caused by epimutations, with early clinical trials restricted to patients who have exhausted all other options. Some argued that medicine routinely advances without fully understanding a drug’s mechanism, so demanding perfection before testing would mean never developing the therapy at all. At the cautious extreme, a minority, particularly basic researchers outside translational work, warned that epigenetic editing could prove less safe than gene editing, since introducing epimutations might reactivate dormant transposons or derail cellular identity in ways scientists can no longer control once edited cells are inside the body. At the opposite pole, a small group envisioned a medical revolution in which epigenetic editors retune multiple genes simultaneously, potentially transforming treatment of autoimmune disease, diabetes, Alzheimer’s and even aging, with speculative applications ranging from skin-rejuvenating creams to cures for HIV and chronic hepatitis B.

The agricultural picture diverged sharply. Plant scientists interviewed for the study did not consider epigenetic editing a commercially viable breeding technology, largely because seed companies require traits that remain stable across generations and environmental conditions, from the controlled greenhouse to the unpredictable open field. Backcrossing can eliminate unwanted off-target changes in plants, removing one of epigenetic editing’s main selling points. Still, respondents sketched hypothetical applications that could eventually prove transformative, such as plant varieties that switch on disease-resistance genes only when a pathogen is actually present, or epigenetic control of flowering, which could dramatically shorten breeding cycles for seed production.

The study’s timing makes its findings particularly pointed. While most respondents questioned whether the technology is ready for real-world deployment, companies are already racing ahead: OMEGA Therapeutics completed a first-in-human clinical trial using epigenetic editing to suppress the oncogene c-MYC in twenty-four participants before filing for bankruptcy in early 2025, and Tune Therapeutics is currently recruiting patients for a trial of an epigenetic silencing therapy for chronic hepatitis B. The authors highlight a mismatch between the private sector’s focus on common, profitable conditions such as high cholesterol and obesity, exemplified by celebrated preclinical results showing durable cholesterol reduction in mice and primates, and the academic community’s caution. They argue that the dominant safety narrative is performing rhetorical work, positioning epigenetic editing as publicly acceptable in ways that may prove premature, and warn of a hype-disappointment cycle reminiscent of the gene therapy backlash of the 1990s. The researchers call for explicit reflexivity within the field, public engagement and citizen participation in shaping the technology’s future, and urge scientists to clearly articulate what evidence is truly needed before epigenetic applications move toward the clinic, arguing that making these visions explicit allows scientists, policymakers and the public to reflect on, adapt and co-create the trajectory of this emerging technology rather than simply inherit whatever future the loudest promises deliver.

Subject of Research: Scientific visions, expectations and reservations regarding epigenetic editing and its responsible innovation

Article Title: Visions, expectations, and reservations in epigenetic editing: towards responsible innovation

Article References: van Baalen, S., Verra, T., Macnaghten, P., Bunnik, E., & Habets, M. G. (2026). Visions, expectations, and reservations in epigenetic editing: towards responsible innovation. Epigenetics Communications, 6(1), Article 6. https://doi.org/10.1186/s43682-026-00047-5

Image Credits: AI Generated

DOI: 10.1186/s43682-026-00047-5

Keywords: epigenetic editing, epigenome, CRISPR-dCas9, gene expression, responsible innovation, gene editing, biotechnology, clinical trials, plant breeding, science and technology studies, research ethics, public acceptance