H-SPAN Summit Links NIH Grants, Lab Timing, and Payer Decisions

At the H-SPAN summit on longevity policy held on September 9, Felipe Sierra, Catherine Kachorovski, and Michael Rinkel discussed how grants, clinical data, and payer decisions form a chain. The US National Institutes of Health (NIH) allocate grants, labs depend on their timing, and insurers or government programs decide whether to pay for treatment based on trial data.

Felipe Sierra, former director of the National Institute on Aging’s Biology of Aging division, explained why his division lacked funding: the number of applications grew while the budget stayed flat. He said he did not ask for more money but wanted NIH to spend its funds elsewhere—specifically on aging‑as‑a‑common‑risk‑factor research already pursued by other NIH institutes. He urged their leaders to redirect their own budgets toward such projects.

Catherine Kachorovski, a professor at the University of Michigan, showed how a grant delay affects a lab. Her application scored in the top 5%; she was initially told she would be funded, but the money was held up because part of the budget had already been pledged to five‑year grants. Universities cut graduate‑student admissions, labs lost funding, and for her lab the delay influenced which staff she could retain.

Michael Rinkel, COO of biotech firm Life Biosciences, shifted the talk to drugs. Phase I trials give early safety and dosage data; later studies test possible efficacy and gather more safety information. He noted that each year 200–300 drug candidates pass Phase I but fail Phase II, so he opposes releasing a drug after only early safety checks.

In the spring the New Hampshire House of Representatives approved centers where drugs can be used after Phase I. This makes Rinkel’s debate practical: payers can decide reimbursement based on data collected after early safety testing. He also warned that lengthy validation is costly, and an analysis of cheap gene‑therapy trials showed why a therapy that is easy to copy may attract no investor for such study—its benefits would be available to all providers.

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Single IV injection of dual‑gene AAV9 extends lifespan in Sandhoff cat model

In a study published Science Translational Medicine, September 9, researchers used a single intravenous injection of an AAV9 vector carrying both HEXA and HEXB genes to treat asymptomatic kittens with a feline model of Sandhoff disease. The vector aims to restore the HexA enzyme needed to break down the lipid GM2 that accumulates in lysosomes.

Untreated animals survived a median of 4.3 months, while low‑dose kittens lived 8.3 months on average. High‑dose treatment extended median survival to 12.4 months, and one cat reached 16 months.

Tremor appeared in untreated kittens around 2.4 months of age. No tremor was observed in the high‑dose group, whereas tremor was delayed in three of four low‑dose kittens.

Sixteen weeks after the high‑dose injection, MRI showed partial preservation of brain structure and CSF levels of neurodegeneration markers were reduced. HexA activity reached approximately 70% of normal in the hindbrain and 120% in the spinal cord.

The liver contained the highest vector copy number, but HexA activity there did not exceed 9% of normal levels. Over longer periods, brain architecture and inflammatory signs in some treated animals began to resemble those of untreated controls.

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Review of 101 Species Highlights DNA Maintenance, Tissue Renewal, Stress Resistance

On 8 September the journal Aging published a review of 101 species with maximum lifespans starting at 250 years, comprising 11 animals and 90 plants.

The authors compared lifespan differences among individuals of the same species and between different species, asking why individuals of a long‑lived species vary in longevity and how these species differ from shorter‑lived ones; they sought processes that recur in both comparisons.

In both comparisons three common directions emerged: DNA maintenance (repairing damage), stem cell properties (enabling cells to divide and generate different tissue types), and stress resistance (helping cells cope with unfavorable conditions and associated harm).

When comparing species, the authors also examined regeneration and tumor suppression; in hydra regeneration replaces all body cells roughly every twenty days, while in common pine and ginkgo root‑growth zone cells retain differentiation ability with age, unlike the shorter‑lived Arabidopsis where this ability declines.

The authors link the three common directions to early developmental stages and germ cells, concluding with the phrase: “Staying young, it seems, is a strategy for long life.”

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Southern Cryonics Stores Seven Bodies in Liquid Nitrogen at Holbrook Facility

On September 10, a Guardian reporter visited the Southern Cryonics facility in Holbrook, New South Wales and observed seven bodies stored in two liquid‑nitrogen dewars. The dewars keep the bodies upside down at -196 °C, and the supplier regularly tops off the tanks to prevent dangerous pressure buildup from evaporating nitrogen.

At the request of its first clients, Southern Cryonics shortened the delivery interval from one month to two‑week cycles. Preparation for storage begins when a patient reaches a terminal state, with CryoPath verifying funding, assembling a standby team and arranging a funeral home.

After legal death, a perfusionist cools the body and adds a cryoprotectant to inhibit ice‑crystal formation; the body is then shipped to Holbrook on dry ice. With direct freezing, the funeral home handles stabilization.

Cryobiologist Saffron Bryant of the Royal Melbourne Institute of Technology notes that vitrification already preserves cells, embryos and blood products, but delivering cryoprotectant evenly throughout whole organs or bodies remains unsolved.

The published Southern Cryonics contract states that continued storage depends on the client organizing and paying for standby, stabilization and transport; failures such as lack of funds, unpaid fees, delays, loss of permit, legal changes or operator insolvency allow the company to refuse or halt cryopreservation, after which the body may be buried, cremated or transferred to the legal custodian.

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Old fibroblasts transfer polarity defect to young cells via ApoD

The bioRxiv, September 10 preprint describes a loop in which ApoD secreted by aged fibroblasts raises SUN1 at the nuclear envelope, disrupting the orientation of young fibroblasts. High SUN1 levels in turn increase ApoD secretion, establishing a positive feedback loop.

Cell polarity requires fibroblasts to align a front‑rear axis, positioning the nucleus and the microtubule‑organizing center. When young fibroblasts were cultured in medium previously conditioned by old cells, they failed to correctly place the nucleus and center after a motility cue, whereas control medium had no effect. Proteomic analysis of the conditioned medium implicated ApoD, and purified ApoD reproduced the polarity defect.

ApoD elevated SUN1 in young fibroblasts, strengthening the SUN1–nesprin‑2 bridge that links the nucleus to microtubules; excess SUN1 blocked proper nuclear positioning. Knocking down SUN1 or disrupting the microtubule‑nucleus tether rescued polarity, and high SUN1 also drove more ApoD release, while SUN1 suppression lowered ApoD secretion.

The defect extended to muscle progenitors: ApoD impaired their ability to form fibers in culture. In vivo, mice received ten days of daily intravenous ApoD injections; on day‑five half underwent muscle injury. Injured muscle showed reduced mass and contractile force versus controls, while uninjured muscle was unchanged.

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Astra AI designs complex robotic arm and paints Golden Gate Bridge in real time

Astra generated 190 ready‑to‑use CAD files in STEP format for assembling a highly complex robotic arm, using just 48 hours of work and ~50,000 lines of Python code. The AI didn’t only draw the geometry; it fully programmed the kinematics, visualized the result with JavaScript, and exported the finished 3D models as GLB files for rendering.

In the second video, Astra was given a physical manipulator, a paint‑filled brush, and a camera for feedback, then tasked with painting the Golden Gate Bridge. The model independently worked out the robot’s kinematics, learned to evaluate the output via the camera, and improved each successive stroke through real‑time trial and error until it produced a coherent painting.

🔗 Source: @solid_state_humanity

Knocking out cGAS in killifish reduces aging markers but does not extend life

On September 9, a study appeared in EMBO Reports on turquoise killifish, a short‑lived fish whose full lifespan can be tracked in a single lab line. cGAS senses cytosolic DNA and triggers inflammatory signaling. The authors identified which of two similar genes functions as cGAS: cGASa produces cGAMP and activates immune genes; they knocked it out with CRISPR.

Early after irradiation, fin cells lacking cGAS showed more γH2AX DNA‑damage markers. Nine days later, these fish had fewer SA‑β‑gal‑positive cells (a marker of stable cell‑cycle arrest) and more EdU‑positive cells (DNA‑synthesis label). Thus DNA‑damage signaling was higher while stable arrest was lower.

In old kidneys, the SA‑β‑gal‑stained area in tubules decreased, and EdU and PCNA (another proliferation marker) were more frequent. No such differences were seen in the intestine, indicating tissue‑specific effects.

Lifespan was measured in 70 knockout and 79 control fish. Median survival was 150.5 days for knockouts versus 143 days for controls; maximum lifespan was 215 days vs 213 days. The proportion of survivors with age did not differ statistically, either overall or when males and females were analyzed separately.

In mice, complete loss of cGAS reduced median lifespan from 2.01 years to 1.64 years. In killifish, the same genetic manipulation shifted several cellular and kidney phenotypes but did not alter the survival curve.

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Borras Recommends Personalizing Exercise, Heat, and Calorie Restriction by Adaptive Reserve

On **September

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Archerships urges human enhancement to coexist with future superintelligence

In a September 12 post, the archerships account argues that humans must strengthen both body and mind to keep pace with forthcoming superintelligence. It proposes a coexistence strategy with AI that will surpass humans in intellectual tasks, resting on two ideas: humans and AI could occupy different environments, and technology could give humans comparable intelligence and the ability to modify their bodies.

The author begins with an analogy—humans displaced animals, so superintelligence might displace humans—but challenges this transfer. He notes that as human capabilities grew, animal protection expanded, and future AI, in his scenario, could operate in environments where biological humans would struggle to survive. He quotes, “If chimpanzees tried to subordinate human actions to chimpanzee interests, such an endeavor would be doomed from the start.” Using this analogy, he explains his distrust of political control over superintelligence, imagining a world government trying to align superintelligence with human interests that could turn against humans. Therefore, he advocates narrowing the ability gap itself.

The second pillar of his scenario is environmental separation. He assumes AI could work on the ocean floor, in space, deserts, and the Arctic—where heat dissipation is easier—while modern AI depends on data centers, power plants, and chip fabs. From this dependence he derives an incentive for AI to expand into other environments while coexisting with humans.

In a March essay on the future of transhumanism, human enhancement was presented as a backdrop for hope in superhuman AI. The author reframes it as a means to reduce the gap between humans and future AI, linking this path to neural interfaces that connect brain to device, memory implants, atomic‑precision nerve‑cell scanning, and

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AI Giants Pretend to Slow Race for Show While Avoiding Real Competition

The heads of OpenAI and Anthropic publicly claim they want to slow the AI race for humanity’s sake, but they are merely putting on a show and currying favor with regulators. Do not be naive enough to believe the wet‑dream narratives about so‑called AI‑safety; they will never admit their own direct gain from such regulations.

Smaller AI startups lack the resources to navigate the bureaucracy that these leaders propose to introduce, as hinted in that touching screenshot in parentheses. In contrast, OpenAI and Anthropic will not feel the impact—they retain the best lawyers and audit experts.

When funds for maintaining data centers eventually run out, they can deflect disappointed investors by citing safety concerns rather than admitting low economic profitability.

Do not trust these performative dialogues on Twitter: first, none of them will actually slow the race beyond the point where they can still compete with China; second, the AI‑safety field is vastly overblown, and fears of powerful AI evaporate if we simultaneously improve humanity.

Today we see an imbalance where only models advance, leaving humans at risk of falling behind AI. To close—or even erase—that gap we need transhumanism, not a brake on AI but an acceleration of human capabilities.

🔗 Source: @solid_state_humanity

Pig kidney protein profiles approach control after clot‑dissolving perfusion

A preprint posted on Research Square, September 11 examined pig kidneys after uncontrolled circulatory arrest. The authors followed four kidneys treated with perfusion drugs and four kidneys from living donors transplanted using the same surgical plan. Tissue samples were taken at removal, after each perfusion phase, and three months after re‑transplantation.

For perfusion, the renal artery received lys‑plasminogen, tissue plasminogen activator (tPA), and antithrombin before connecting the organ to machine perfusion with cold and warm phases. A total of 8 011 protein groups were measured across all samples.

In a pre‑selected panel of 93 proteins, 39 showed significant changes after correction for multiple testing. Five common plasma proteins accounted for 91% of the total reduction, with fibrinogen and plasminogen chains continuing to fall during the cold phase in all four treated kidneys, reflecting fibrin fragment clearance.

Three months later, the overall protein profile of the treated kidneys resembled that of living‑donor kidneys, although differences remained. Extracellular‑matrix proteins increased, which the authors interpret as post‑injury remodeling. This work adds a temporal map of tissue changes from explant to the three‑month point to the group’s earlier report on three‑month function of such transplanted kidneys.

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Study finds two independent dimensions of tissue aging across 16 human organs

On 13 September the authors posted a preprint on bioRxiv, 13 September analysing 14,788 microscopic slices from 16 organs of 980 posthumous donors in the GTEx project. They segmented about ~3.5 billion cells and tracked how their numbers and spatial arrangement change with age.

Tissue can be described by counting each cell type and seeing how they assemble into working patches such as intestinal crypts, vascular niches, or connective‑tissue zones. This layout determines which cells touch each other and what structure the tissue forms.

From individual cells they built groups of neighbours and identified recurring tissue patches — functional units — finding 236 distinct types. Of these, 62 showed a significant shift in proportion across the donor age range, with dense, specialist‑cell regions tending to shrink and looser, immune‑ and connective‑cell areas tending to expand.

When they tried to predict those shifts using only changes in the abundance of each cell type, the model explained just R² = 0.07 of the observed variation. Thus, cellular composition and spatial organization appear as separate, measurable dimensions of age‑related tissue remodeling in this dataset.

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OmniTCR: Single 113‑M‑parameter model predicts T‑cell antigen recognition and designs candidate receptors

A preprint released on 13 September on bioRxiv describes the OmniTCR model, which contains 113 million parameters. It was trained on 328 million immune sequence records, ranging from single receptors to rare full receptor‑peptide‑HLA complexes.

The model learns to predict the next token in a sequence where peptide, HLA, and the α‑ and β‑chains of the T‑cell receptor are separated by boundary tokens. By presenting the components in different orders — peptide‑HLA followed by receptor chains, or the reverse — OmniTCR can both generate candidate receptors for a given target and evaluate how well a known receptor matches that target. This setup lets it leverage both scarce full complexes and abundant single‑chain data for a unified task.

To test generalization, the authors held out peptides never seen during training. On 642 peptide‑β‑chain pairs OmniTCR achieved an AUPRC of 0.7009, and on 141 full peptide‑HLA‑receptor complexes an AUPRC of 0.8235, outperforming the strongest comparison models by 0.3396 and 0.3451, respectively.

For receptor design, OmniTCR constructs the CDR3β region of the β‑chain. Candidates are scored against a given peptide‑HLA pair and ranked by the difference to a null input score. In the top‑100 lists for 20 targets, the average fraction of shared sequences fell from 0.0870 to 0.0323, showing that the target reshapes the candidate pool.

For seven complexes with peptides outside the training set, the authors used AlphaFold 3 to model the candidate structures and compared their structural confidence. Overall, the model learns inter‑component relationships from the full data corpus, transfers to novel peptides, and produces a ranked list of candidates ready for experimental validation.

bioRxiv, 13 September

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Cellectis halts two CAR-T programs, shifts resources

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ScMLEAge cell‑age estimator leaks test data in published code

ScMLEAge is a method that estimates a cell’s age by comparing its RNA‑molecule counts to age‑specific profiles built from donor mice. According to an article published npj Aging on 12 September, the program assigns each cell to an age group based on the number of RNA molecules read from its genes. They used 10 males from 9 tissues from the Tabula Muris Senis dataset.

The method creates age profiles by summing RNA counts of cells from the same age group for each cell type, then

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Atlas of short proteins in human frontal cortex reveals abundant micro-MKKS63

The study published in Nature Aging, September 14 analyzed 610 postmortem frontal cortex samples and identified 4,321 short proteins using mass spectrometry and ribosomal profiling. Of these, 3,217 were absent from the manually reviewed UniProt section, while 1,067 showed strong spectral matches to predicted sequences.

The gene MKKS, annotated with a 570‑aa protein, most frequently yielded a shorter isoform, micro-MKKS63 (63 aa), which received over 1,000 spectral matches. Ribosomal profiling confirmed that cells translate the RNA region encoding micro-MKKS63, and its levels were reduced in the frontal cortex of symptomatic Alzheimer’s disease cases.

In the human microglial line HMC3, micro-MKKS63 localized to mitochondria. CRISPR‑mediated disruption of the micro‑MKKS63‑encoding region in two independent clones decreased basal and maximal oxygen consumption and energy‑linked respiration.

These results show that detecting short proteins separately is essential in brain tissue, as they can be the primary detectable product of a gene and directly influence cellular function.

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APOE ε4 carriers reveal distinct DNA associations with Alzheimer's disease

On September 14, researchers published a study in Nature Genetics that stratified Alzheimer’s patients

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Using organ perfusion time to deliver protective drugs before transplant

On 14 September, a scientific comment proposed using the time when a donor organ is connected to a perfusion machine to deliver a drug intervention. The idea stems from a work in Cell about the experimental compound FXT-001, which protects cell membranes from oxidative damage.

Machine perfusion pumps oxygenated fluid or blood through the extracted organ, keeping it outside the body and allowing its function to be assessed before transplantation. The comment suggests administering the drug during perfusion and measuring its effect by functional markers.

Damage begins when the organ is deprived of oxygen and nutrients, and worsens after blood flow is restored because iron accelerates lipid peroxidation of cell membranes. In 116 liver transplant recipients, malondialdehyde, a marker of lipid oxidation, peaked 30 minutes after reperfusion and its level correlated with AST, a laboratory indicator of liver injury.

FXT-001 chelates iron and blocks the chain‑radical reactions in membrane lipids, so it was tested precisely on this damage mechanism. In pig livers, adding FXT-001 to the cold‑storage solution lowered AST release during subsequent perfusion; in pig lungs, adding the drug to the perfusion fluid at the start reduced water accumulation.

In five pairs of human lungs deemed unsuitable for transplant, the organs were perfused simultaneously: one lung received FXT-001, the other a control solution. This paired design reduces donor variability, and the lungs treated with FXT-001 showed less excess water and weight gain and better preservation of inflation capacity.

The comment concludes that delivering the drug locally during perfusion and assessing organ function before transplant could improve outcomes. This approach would turn the perfusion period into a therapeutic window.

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ChASE37 enzyme aids human neural cell survival in rat stroke model

On September 9, researchers reported results from an ischemic stroke model in rats. Human neural progenitors — cells that can develop into neurons — survived for 4 weeks in 5 of 8 animals that received the cells together with the enzyme ChASE

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Norn Group Reopens Talent Bridge for International Aging Researchers

On September 12, Norn Group opened enrollment for its updated Talent Bridge program, which is aimed at individuals living outside the United States who want to work on aging research. The initiative connects candidates with mentors, the Longevity Nexus community, and potential host organizations in the US.

After applying, a candidate proposes a project; if selected, they complete the work in individualized stages totaling about 100 hours over a period of 3 weeks to 4 months. Upon finishing the collaborative project, the participant receives a stipend of roughly $10,000.

Norn first launched Talent Bridge in 2022. The program includes the Longevity Nexus community for peer exchange and mentorship, and offers help with legal, logistical, and visa matters—including guidance on the O‑1 visa for individuals with extraordinary ability.

Early participants illustrate the program’s impact: Marton Meszaros investigated the missing human data and validation methods needed for aging biomarkers and is now launching a company in the United States. Nicholas Di Leo prepared a review of rapamycin clinical trials. As Norn states, “We look for potential and focus, not formal qualifications.”

Talent Bridge structures the entire pathway around a completed, publishable project. This gives candidates concrete results to discuss with mentors and prospective host organizations. The program then provides networking and relocation support to facilitate the move to the US.

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Matt Kaeberlein Questions Genflow's Early Claim of Age Reversal in Dogs

On 8 September Genflow announced that it had met its pre‑specified primary endpoint in a trial of 24 beagles older than ten years. The company said the GRIM DNA‑methylation clock showed a lower biological age in the treated dogs compared with the saline‑treated group, and it pledged to present detailed results on 1–2 October.

On 12 September biogerontologist Matt Kaeberlein questioned why the outcome was released before the full data were available. He noted that, as far as he could see, no preprint or dataset existed to evaluate the claim of age reversal.

The study randomly assigned the 24 beagles to four groups, with assessors blinded to treatment. Three groups received different gene‑therapy variants, while the control group received saline. The primary endpoint was the GRIM clock, and Genflow plans to disclose the full dataset at the Animal Longevity Summit in Toronto on 1–2 October, with DNA‑clock and muscle‑histology results slated for 2 October.

Kaeberlein had previously discussed in August whether a shift in such a clock could be taken as evidence of an intervention’s effect, and he asked for the data needed to verify the claim of a 'reduction of biological age'. He highlighted the Longevity.Technology headline: 'Genflow gene therapy reverses aging in dogs'.

He argued that only after the 2 October release of the DNA‑clock and muscle‑histology measurements can the primary‑endpoint claim be properly checked against the underlying data.

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