The timing of the study is significant. NASA is currently planning multiple missions with durations exceeding six months in space, spanning commercial activity in low Earth orbit, the Artemis IV mission that will carry the first crewed flight to the lunar south pole in 2028, and the development of sustainable surface capabilities on the moon in preparation for eventual human journeys to Mars. Each of these endeavors will demand more human participation and more cumulative time spent in extraterrestrial environments, and each will draw on crews selected precisely because of their exceptional physical fitness and optimal health. The paradox highlighted by the new research is that the very individuals best equipped to endure the rigors of spaceflight may nonetheless carry forward hidden skeletal vulnerabilities that standard post-flight assessments do not fully capture.

The underlying physiology is well established, even if its long-term consequences have been harder to quantify. Muscle and bone loss in the microgravity environment of space is a common physiologic phenomenon among astronauts, and it is understood as an adaptive response to disuse. In the absence of gravitational loading, the skeleton receives far less mechanical stimulation than it does on Earth, and the body responds by reducing bone formation while resorption continues, gradually eroding bone mass and altering the internal architecture of load-bearing structures such as the hip. What makes this process insidious, as lead investigator Jean D. Sibonga, PhD, of NASA’s Johnson Space Center has noted, is that humans do not feel the effects of bone loss. An astronaut can return from space, feel stable, and even believe themselves fully recovered, then resume physically demanding activities despite underlying skeletal changes caused by prolonged disuse.

That disconnect between how astronauts feel and what their bones can actually withstand is central to why the new findings matter. A better understanding of bone health after spaceflight, the researchers argue, could help astronauts, patients, and clinicians assess long-term health concerns, determine appropriate care, and reduce the risk of injury. The hip is a particularly consequential site in this regard. Hip fractures are among the most serious fragility fractures in any population, associated with substantial morbidity, long recovery periods, and elevated mortality risk, especially when they occur at ages earlier than typical. A fracture rate that rises after long-duration flight, and that emerges at younger ages than would be expected in the general terrestrial population, therefore represents a warning signal that extends well beyond the immediate post-mission period.

One of the persistent obstacles in spaceflight medicine has been the sheer difficulty of gathering statistically robust data. Matthew T. Drake, MD, PhD, of the Endocrinology and Metabolic Bone Disease Service at the Hospital for Special Surgery in New York, and co-author of an accompanying editorial in the same journal, observed that while data to date on bone loss associated with spaceflight are consistent, a major limitation is accuracy, because astronaut cohort sample sizes are small and spaceflights are rare. With only a few hundred people having ever flown in space, and only a subset of those undertaking missions longer than 90 days, conventional epidemiological comparisons often lack the statistical power to detect meaningful differences in fracture outcomes. Small cohorts and rare events make it easy for real effects to hide within the noise.

To overcome this statistical limitation, the investigators took a different analytical approach. They surveyed a cohort of US-based astronauts for all fractures reported during annual clinical exams, assembling a longitudinal record of skeletal outcomes across careers that spanned missions of varying lengths. They then analyzed these data using Bayesian probabilistic modeling, a framework that allows researchers to draw more stable inferences from small samples by incorporating prior knowledge and quantifying uncertainty explicitly. The results were striking in their specificity. While the study did not find a higher incidence rate for fractures in general, the incidence rate for hip fractures in astronauts was increased after a long-duration spaceflight of more than 90 days. The effect was not a diffuse elevation of injury risk across the skeleton, but a concentrated signal at one of the body’s most mechanically critical sites.

Two features of that signal stand out. First, the increased hip fracture rate occurred at a younger age than would be expected in a non-astronaut terrestrial population, meaning astronauts were experiencing these injuries earlier in life than standard fracture epidemiology would predict. Second, the rate was greater than the rate observed before a long-duration mission, or with no spaceflight exposure at all, which points to the spaceflight itself, rather than age or occupational hazards alone, as the differentiating factor. Moshe Gertzulin, MD, also of the Endocrinology and Metabolic Bone Disease Service at the Hospital for Special Surgery and co-author of the accompanying editorial, summarized the implication: taken together, the finding of hip fracture occurrence at an age earlier than expected after long-duration spaceflight is clinical evidence that spaceflight-induced bone loss can lead to real long-term fracture consequences, which should be addressed accordingly.

The study’s authors argue that these conclusions carry direct implications for how space agencies monitor skeletal health. Dr. Sibonga emphasized the need to expand NASA’s current bone surveillance program beyond dual-energy X-ray absorptiometry, or DXA, measurements of bone mineral density, the long-standing standard for assessing skeletal status. DXA provides a two-dimensional summary of density but offers limited insight into the three-dimensional structure of bone, which is increasingly recognized as a critical determinant of fracture resistance. NASA has recently begun ordering quantitative computed tomography scans before and after spaceflight, a modality that can provide more detailed information about different areas of the bone and about whether astronauts have truly fully recovered. Without that finer-grained insight, astronauts could risk placing too much strain on bones that have not yet regained their preflight condition, precisely the scenario in which a fragility fracture is most likely to occur.

Beyond surveillance, the investigators advocate for prophylactic countermeasures designed to preserve the baseline, pre-flight skeletal health of the astronaut, rather than attempting to reverse damage after the fact. A fuller characterization of spaceflight-induced changes to bone mass, density, structure, and microarchitecture will determine which interventions, whether pharmaceutical agents, exercise regimens, or dietary adjustments, are most beneficial for long-term skeletal health. Current in-flight countermeasures centered on resistive exercise have slowed but not fully prevented bone deterioration on long missions, and the new fracture data suggest that residual deficits matter over timescales of years, not weeks. Identifying the right combination of countermeasures before crews embark on months-long lunar surface stays and multi-year Mars transits could mean the difference between a mission that ends with healthy crews and one that seeds decades of orthopedic problems.

The broader significance of the study extends beyond the astronaut corps. The disuse-related bone loss that astronauts experience is, in essence, an accelerated model of the immobilization and unloading that affects patients on Earth, from those confined to bed rest to individuals with spinal cord injuries or age-related osteoporosis. Insights gained from studying spaceflight-induced skeletal changes, and from the advanced imaging and modeling techniques being deployed to study them, may inform how clinicians on Earth assess and manage fragility in their own patients. For now, the message from Mayo Clinic Proceedings is unambiguous: the skeleton keeps a record of every day spent in microgravity, and for missions longer than 90 days, that record includes a heightened risk of hip fracture that surfaces earlier in life than anyone would want. As humanity prepares to spend longer stretches of time on the moon and beyond, safeguarding the bones that carry astronauts home has become a scientific challenge worthy of the ambition of the missions themselves.

Subject of Research: Long-duration spaceflight-induced bone loss and hip fracture risk in astronauts

Article Title: Study links 90+-day spaceflights to higher rates of hip fractures in astronauts

Article References: Study links 90+-day spaceflights to higher rates of hip fractures in astronauts. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: astronauts, hip fracture, bone loss, microgravity, spaceflight, NASA, Mayo Clinic Proceedings, bone mineral density, quantitative computed tomography, osteoporosis, Artemis, space medicine

Severe combined immunodeficiency is a group of inherited disorders characterized by impaired lymphocyte development, and mutations in more than twenty genes have been implicated in the condition, including CD3D, IL7R, IL2RG, RAG1, RAG2, PRKDC, LIG4, and DCLRE1C, the gene that encodes Artemis. Affected infants typically present with chronic diarrhea, oral thrush, skin rashes, and recurrent, refractory infections. Without early diagnosis and intervention, the disease can lead to life-threatening complications and a high risk of mortality. Since the 1960s, hematopoietic cell transplantation has been the primary treatment, and thousands of infants have been treated worldwide, but the Artemis-deficient form of the disease poses particular challenges that have driven researchers to seek alternatives.

Artemis is an endonuclease that resolves DNA hairpin intermediates during V(D)J recombination, the genome-scrambling process that generates the diverse repertoire of antigen receptors on lymphocytes. After the RAG1/2 recombinase complex cleaves recombination signal sequences, Artemis, activated by DNA-PKcs, nicks the closed DNA hairpin coding ends, creating a 3-prime overhang that primes subsequent junctional diversification. The enzyme also acts as a caretaker of genomic integrity through its participation in the non-homologous end-joining DNA repair pathway. When Artemis is absent, T and B cell development is arrested, producing a radiation-sensitive form of SCID. The clinical spectrum is highly heterogeneous: null mutations generally cause classical SCID with complete arrest of lymphocyte development, while hypomorphic alleles retaining partial nuclease activity can give rise to atypical phenotypes, including Omenn syndrome and leaky SCID.

The transplantation route itself is complicated by the very biology of the disease. Patients with radiosensitive SCID are systemically sensitive to alkylating agents, the standard myeloablative drugs used before transplantation to eradicate recipient hematopoietic stem cells. Clinical studies have also indicated that ART-SCID patients remain hypersensitive to ionizing radiation and suffer more infections long after receiving an allogeneic transplant. Even with an HLA-matched sibling donor, T and B cell reconstitution after transplantation is not as efficient in ART-SCID patients as it is in other SCID genotypes. Gene delivery strategies using lentiviral vectors carrying wild-type Artemis cDNA have been explored, and replacing a strong viral promoter with the endogenous human Artemis promoter achieved robust immune recovery in affected infants after in vivo transduction of hematopoietic stem cells. However, the lingering safety concern of insertional mutagenesis, in which semi-randomly integrating vectors may activate oncogenes, persists. Meanwhile, CRISPR-Cas9 mediated homology directed repair, another gene correction approach, remains difficult to apply clinically because quiescent hematopoietic stem cells are intrinsically resistant to HDR and the error-prone NHEJ pathway competes for repair, resulting in low efficiency.

Against this backdrop, base editors have emerged as a compelling alternative. Cytosine base editors employ cytidine deaminases such as rat APOBEC1 to convert C•G base pairs to T•A via a C-to-U intermediate, while adenine base editors use evolved adenine deaminases to convert A•T to G•C through A-to-I deamination. Both consist of an engineered deaminase fused to a Cas9-derived module for guide RNA-directed DNA targeting, and neither requires a donor DNA template or creates a double-strand break. Base editors have already entered clinical trials for sickle cell disease, beta-thalassemia, and familial hypercholesterolemia, and have been used to develop universal CAR T cells. In a striking precedent, researchers delivered a cytidine base editor by electroporation into human hematopoietic stem cells to correct the CD3D mutation that causes another form of SCID, achieving approximately 71.2 percent pathogenic-allele repair.

To systematically identify suitable editing targets for ART-SCID, the research team first compiled previously reported pathogenic point mutations in Artemis and mined the ClinVar database for additional disease-associated variants, filtering out 41 mutations documented as pathogenic and highly conserved throughout Artemis evolution. Using an established Artemis-knockout 293T cell line and a coding-joint reporter assay, an extrachromosomal V(D)J recombination system in which functional Artemis enables GFP expression quantified by flow cytometry, the team screened candidate variants. They newly identified four mutations, G6E, E10G, F19L, and L110R, that severely impair Artemis activity, reducing both its exonuclease activity toward single-stranded DNA and its endonuclease activity toward 3-prime overhang and DNA hairpin substrates. Structural modeling based on the wild-type Artemis crystal structure further revealed that mutations such as G118V, G135E, and L110R substantially reduce protein stability, and that G118 coordinates a conserved water molecule bridging residues critical for activity across the related SNM1 family members SNM1A and SNM1B.

From this catalog, the team selected three loss-of-function mutations amenable to correction by established base editors: c.49G>A (D17N) and c.404G>A (G135E), both targetable by adenine base editors, and c.181T>C (C61R), a representative cytidine-base-editor target. The clinical stakes of these variants are well documented. The c.49G>A mutation was identified in a Japanese SCID study in which two of eight patients harbored the homozygous variant, presenting before six months of age with severe infections and profound T cell deficiency. The c.404G>A mutation was reported in a study of four ART-SCID patients, two of whom carried the homozygous variant with a T-negative, B-negative, NK-positive immunophenotype; one presented with persistent varicella-zoster virus infection, and both ultimately succumbed to severe complications including multiorgan failure. Before editing, the team also assessed predicted bystander substitutions within the editing windows, finding that S62L moderately attenuates activity, I16M and Y133C cause minor reductions, T134A has negligible impact, and I16V has no detectable effect, confirming the three sites as suitable and comparatively safe targets.

The ex vivo editing results were encouraging. For the c.181T>C mutation, the team tested several cytidine deaminases incorporated into the BE4max backbone, including rat APOBEC1, APOBEC3A, and evoFERNY, alongside narrow-window variants and a combination of rat APOBEC1 with SpRY-HF1, a PAM-relaxed, high-fidelity Cas9 variant. Deep sequencing showed that rAPOBEC1-SpRY-HF1-BE4max paired with a suitable guide RNA achieved approximately 50 percent editing efficiency at the target site, with no significant off-target activity at any of five computationally predicted genomic loci per guide, as assessed by targeted deep sequencing and CRISPResso2 analysis. Flow cytometry confirmed that editing partially restored Artemis endonuclease activity in the mutant cells. Haplotype-level analysis of bystander mutations revealed that most co-occurring substitutions were silent due to codon degeneracy, with the predominant functional bystander being S62L, which only moderately reduces activity.

For the adenine base editor experiments, five editors were tested, including ABE7.10, ABEmax, ABE8e, ABE8e-SpRY-HF1, and ABE8e-NRRH. ABE8e achieved approximately 35 percent correction at the c.49G>A site, comparable to ABE8e-NRRH with a PAM-relaxed guide, and flow cytometry demonstrated significantly increased Artemis activity following correction, with no significant off-target mutations at predicted sites and a dominant bystander, I16V, that does not impair function. The c.404G>A site proved more difficult: ABE8e and ABE8e-SpRY-HF1 reached roughly 20 percent editing efficiency, but Artemis activity was not restored. The culprit appears to be a frequent bystander mutation, D136G, which completely abolishes enzyme activity. The authors suggest that prime editing, which couples Cas9 to a reverse transcriptase and an exogenous RNA template to enable precise nucleotide correction with markedly reduced bystander effects, may be better suited for mutations of this type.

The authors are candid about the limitations of the work. All editing experiments were performed in 293T cells, which provide a convenient and robust evaluation system but do not fully recapitulate the biology of human hematopoietic stem and progenitor cells, which exhibit distinct DNA repair pathway preferences and greater sensitivity to editing-associated cytotoxicity. Future studies in patient-derived CD34-positive cells will require clinically relevant delivery methods such as electroporation of ribonucleoprotein complexes, specialized culture conditions to preserve stemness, and long-term engraftment assays in immunodeficient mouse models to confirm safety and self-renewal capacity. The off-target analysis was also limited to predicted sites, and genome-wide evaluation will be needed. Moreover, base editing cannot address patients with homozygous large genomic deletions, though correcting a single allele in compound heterozygous patients is supported by the observation that parents carrying only one mutant allele remain asymptomatic. Nevertheless, by linking precise nucleotide correction to functional recovery of a critical immune gene, the study establishes a theoretical foundation for base-editing therapies for ART-SCID and related monogenic disorders, and underscores how rapidly evolving editor toolkits, including newer glycosylase-based editors capable of C-to-G and T-to-G conversions, continue to expand the range of mutations that may one day be corrected at the bedside.

Subject of Research: Base editing correction of Artemis gene mutations as a potential gene therapy approach for Artemis-deficient severe combined immunodeficiency

Article Title: Base editing of Artemis mutations ex vivo sheds light on gene therapy for Artemis-deficient SCID

Article References: Base editing of Artemis mutations ex vivo sheds light on gene therapy for Artemis-deficient SCID. (n.d.). https://doi.org/10.1007/s44307-026-00115-w

Image Credits: AI Generated

DOI: 10.1007/s44307-026-00115-w

Keywords: Artemis, ART-SCID, base editing, CRISPR, cytidine base editor, adenine base editor, V(D)J recombination, severe combined immunodeficiency, gene therapy, ex vivo editing, DCLRE1C, off-target effects

The stakes are unusually high because electricity on the Moon is not a convenience but a survival system. Every spacecraft subsystem, from life support to propulsion to scientific instrumentation, depends on electrical power, and a review of spaceflight history shows that electrical system failures remain a leading cause of spacecraft losses even after decades of refined safety regulation, expanding documentation requirements, and escalating mission costs. On the lunar surface, a power outage that would be an inconvenience on Earth can lead to catastrophic equipment failure and astronaut health emergencies within a matter of hours, when thermal management and life support cease functioning in an environment where nighttime temperatures plunge below 100 Kelvin.

Williams argues that for the first time in history, private companies will begin offering power provision as a service on the lunar surface, and that the coming mismatch between power producers and power consumers creates a genuine engineering problem. Generators and end users vary widely in power quality, risk tolerance, and demand profiles, which can force customers to dedicate significant mass budget to their own power subsystems even when shared infrastructure exists. According to NASA’s risk classification framework, payloads are risk-classified on Earth before launch, and any grid intended to serve payloads with a risk designation above sub-class D must therefore offer semi-autonomous functionality, distributed sensing, and fault tolerance from its very first day of operation. A grid with single points of failure or ineffective autonomy simply cannot safely power the major loads of upcoming missions, including habitats, surface mobility systems, resource extraction technology, and stand-alone science payloads.

The paper begins by walking through the anatomy of an electrical grid: generation, storage, transmission, distribution, and end-user technology. On Earth, fossil fuel and nuclear plants account for roughly 78.6 percent of United States generation, with hydroelectric, wind, and solar filling out the remainder, and the rise of distributed photovoltaic generation has already forced grid engineers to develop entirely new fault protection schemes for networks that no longer carry current in just one direction. Williams contends that this terrestrial experience with distributed solar is directly relevant to the Moon, where initial generation will likewise be dominated by solar arrays, blurring the traditional boundary between high-voltage transmission and local distribution because the distances involved are comparatively short and the generator fleet is small and dispersed.

For lunar generation specifically, the review highlights two NASA programs as the current state of the art: the Vertical Solar Array Technology effort, which produced mobile, vertically oriented 10-kilowatt solar arrays designed for cyclic operation in the persistently lit polar regions, and the Fission Surface Power program, targeting self-contained reactor systems of 40 kilowatts and above that could be deployed almost anywhere on the lunar or Martian surface. Nuclear options promise constant power independent of sunlight, but they carry drawbacks including fuel security requirements, radiation shielding near human activity, maintenance concerns, and thermal rejection challenges. Energy storage will likely begin with conventional space-rated lithium-ion batteries, including cells developed for cryogenic hibernation that can survive below 100 Kelvin, before space-rated flywheels and other technologies join the mix as lunar material production matures.

On the transmission question, the paper weighs wired against wireless architectures and finds that each may compensate for the other’s weaknesses. NASA’s Glenn Research Center has evaluated radial, ring, and mesh wired networks across a range of voltages and frequencies, concluding that dual-line fault tolerance through mesh networks may be necessary when humans or high-value robotic systems are on the line, even though the simplest grid would be radial. Open questions persist over alternating current versus direct current transmission, over conductor materials, where aluminum extracted from polar regolith could eventually enable in-situ cable production, and over whether cables should be buried, laid on the surface where they threaten astronauts and rovers with tripping hazards, or strung overhead where they are vulnerable to breaks and difficult to repair. Radiation-tolerant power electronics based on wide band gap semiconductors remain at low technology readiness, and semiconductor converters are still vulnerable to total ionizing dose effects and single-event upset.

Wireless power transfer, particularly laser beaming, emerges as a serious contender precisely because the Moon lacks the constraints that killed comparable concepts on Earth. There is no atmosphere to attenuate beams, no existing wired infrastructure to compete with, and a premium on mass, which matters because even high-voltage cables can become prohibitively heavy for transmission across tens of kilometers. Laser systems can in principle deliver substantial power over distances exceeding 1,000 kilometers, but they suffer from poor conversion efficiency, thermal rejection challenges at both ends, and low overall technology readiness. Surface-based optical links need relays to reach over the horizon, with less than 2.5 kilometers of range at ground level but more than 10 kilometers using relay towers tens of meters tall. Relay mirrors are far lighter than full receiver-retransmission stations but demand precise beam steering and independent health-monitoring sensors, and dust melted into mirror surfaces during operation can degrade efficiency. Because generation and consumption are decoupled in wireless systems, every element needs its own dedicated sensors, controllers, and communications, since the transmitter cannot know how much power actually arrived at the receiver.

The review then systematically catalogs failure modes, borrowing directly from terrestrial experience. Equipment malfunction, overloading, voltage fluctuation, and line faults all have lunar analogs: dust and micrometeorite impacts replace vegetation and weather, thermal mismatch between lit and shadowed regions replaces lightning, and human error remains human error. Detection relies on the same sensor families used on Earth, with temperature sensors likely to be the most common because of their low cost and the extreme importance of catching thermal runaway, supplemented by current transformers, power quality analyzers, vibration sensors that become indispensable once reactors come online, and reflectometry techniques that pinpoint the location of breaks in distribution lines. Crucially, the paper notes that a lunar grid will be built from the ground up, allowing prognostics and health management systems to be integrated with automation and fault management from the start rather than retrofitted onto legacy hardware. Repair is the hardest constraint of all: extravehicular activity requires long preparation and months of training, resupply takes weeks, and robots alone are unlikely to complete complex repairs before cascading damage occurs, so systems must either be heavily redundant or designed for repair by teleoperated robots or astronauts working through bulky gloves.

The paper’s original contribution is a proposed control architecture built on NASA’s Platform for Autonomous Systems, which distinguishes between brute-force autonomy, in which predefined responses cover anticipated scenarios, and thinking autonomy, in which software builds its own models of system health and devises responses to anomalies it was never explicitly programmed for. Williams envisions a solar-based wired grid organized into Local Agents, each managing a functional group of elements with its own sensors, coordinated by a Global Agent that schedules tasks, prioritizes fault isolation, and can disconnect damaged branches before other proposed tasks. Endpoint users, from science instruments drawing 0.2 to 1 kilowatt, to habitats needing 2 to 20 kilowatts, to resource extraction systems consuming 22 to 60 kilowatts or more, could connect behind a demarcation point and draw power without interacting with the grid’s control scheme. Demand modeling in the paper suggests Artemis-related loads could exceed 140 kilowatts by 2032, while currently planned generation delivers only about 50 kilowatts, though adjusted assumptions on element lifetimes and initial resource-extraction demand show that two additional 10-kilowatt vertical solar arrays could enable genuine grid development within the decade. Human operators will still be essential, requiring new classes of interfaces to monitor lunar-tolerant equipment and intervene when autonomous algorithms encounter sensor data outside their training envelope. If the analysis holds, the transition from single-lunar-day sorties to multi-year, night-surviving lunar operations may hinge less on new power sources than on the unglamorous work of switches, sensors, and software that keep a grid alive when the nearest repairman is a quarter million miles away.

Subject of Research: Architectural concepts for a robust, autonomous electrical microgrid to support long-term human and robotic operations on the lunar surface.

Article Title: Lunar electrical grid development concepts

Article References: Williams, H. (2026). Lunar electrical grid development concepts. Space and Planetary Resources, 2(1), Article 10. https://doi.org/10.1007/s44461-026-00016-9

Image Credits: AI Generated

DOI: 10.1007/s44461-026-00016-9

Keywords: lunar grid, microgrid, space power systems, fission surface power, vertical solar arrays, laser power beaming, fault management, grid autonomy, energy storage, Artemis, in-situ resource utilization, lunar night