Borras Recommends Personalizing Exercise, Heat, and Calorie Restriction by Adaptive Reserve
On **September
🔗 Read original →
On **September
🔗 Read original →
PubMed Central (PMC)
A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity
Caloric restriction (CR), energy intake reduced below ad libitum (AL) intake, increases life span in many species. The implications for humans can be clarified by randomized controlled trials of CR. To determine CR’s feasibility, safety, and effects ...
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
🔗 Read original →
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
🔗 Read original →
PubMed Central (PMC)
A high-performance speech neuroprosthesis
Speech brain–computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speech into text1,2 or sound3,4. Early demonstrations, although promising, have not ...
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
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
Telegram
Solid State Humanity
Главы двух крупнейших ИИ-компаний согласны притормозить гонку во благо человечества показушно и превентивно лебезят перед регуляторами. Вы ведь не настолько наивны, чтобы поверить во влажные фантазии про т.н. AI-safety?
А ещё они никогда вам не скажут свою…
А ещё они никогда вам не скажут свою…
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.
🔗 Read original →
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.
🔗 Read original →
PubMed Central (PMC)
Lysis of cold-storage-induced microvascular obstructions for ex vivo revitalization of marginal human kidneys
Thousands of kidneys from higher-risk donors are discarded annually because of the increased likelihood of complications posttransplant. Given the severe organ shortage, there is a critical need to improve utilization of these organs. To this end, ...
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.
🔗 Read original →
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.
🔗 Read original →
bioRxiv
A single-cell view of human tissue aging reveals architectural decline beyond cellular composition
Aging reshapes the human body at the cellular level, yet how cell identity, morphology, and spatial organization remodel across organs and the adult lifespan remains poorly mapped, at a scale and lifespan coverage that molecular spatial assays cannot yet…
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
🔗 Read original →
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
🔗 Read original →
bioRxiv
OmniTCR: a foundation model unifying T cell receptor recognition prediction and conditional sequence generation
T cell receptor (TCR) recognition prediction and receptor generation are traditionally modelled separately, leaving vast TCR sequence collections disconnected from smaller TCR-peptide-MHC datasets. Here we present OmniTCR, a 113-million-parameter autoregressive…
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
🔗 Read original →
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
🔗 Read original →
PubMed Central (PMC)
A Single Cell Transcriptomic Atlas Characterizes Aging Tissues in the Mouse
Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death1. Despite rapid advances over recent years, many of the molecular and cellular processes which underlie ...
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.
🔗 Read original →
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.
🔗 Read original →
Nature
A microprotein atlas of the human frontal cortex in Alzheimer’s disease
Nature Aging - A new atlas identifies 1,067 unannotated microproteins in the human frontal cortex with strong spectral grades. A subset is differentially expressed in Alzheimer’s disease...
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
🔗 Read original →
On September 14, researchers published a study in Nature Genetics that stratified Alzheimer’s patients
🔗 Read original →
Nature
APOE-stratified genome-wide association analyses provide insights into the genetic etiology of Alzheimers’s disease
Nature Genetics - Genome-wide association analyses of Alzheimer’s disease stratified by APOE carrier status identify variants whose effects are attenuated or augmented by the ε4 risk...
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.
🔗 Read original →
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.
🔗 Read original →
Nature
Ferroptosis blockade: beyond preservation to active graft therapy
Signal Transduction and Targeted Therapy - Ferroptosis blockade: beyond preservation to active graft therapy
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
🔗 Read original →
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
🔗 Read original →
PubMed Central (PMC)
Co‐Delivery of Sustained Release Chondroitinase ABC‐37 With Human iPSC‐Derived Neural Progenitors Promotes Transplant Survival…
Stroke is a leading cause of disability worldwide, yet effective treatments to regenerate damaged tissue remain elusive. We investigated tissue regeneration and functional recovery post‐stroke in an animal model with a combinatorial approach ...
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.
🔗 Read original →
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.
🔗 Read original →
Substack
Norn Groups’s Talent Bridge: Come to America and make the world live longer
We sponsor the best talent from around the world with grants and networking, to come to America and pursue projects that advance longevity.
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.
🔗 Read original →
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.
🔗 Read original →
X (formerly Twitter)
Matt Kaeberlein (@mkaeberlein) on X
Another example of "science by press release", which isn't really science at all.
A publicly traded company puts out a press release announcing amazing results for their gene therapy *before* e…
A publicly traded company puts out a press release announcing amazing results for their gene therapy *before* e…
Sinclair and Brenner Debate Why SIRT1‑Targeting Drug Programs Were Halted
On September 10 a study on the compound SRT1720 was released; it was tested on rat kidney cells and on rats with sepsis. On September 1
🔗 Read original →
On September 10 a study on the compound SRT1720 was released; it was tested on rat kidney cells and on rats with sepsis. On September 1
🔗 Read original →
PubMed Central (PMC)
Pharmacological activation of SIRT1 alleviates sepsis-associated acute kidney injury by improving renal mitochondrial energy metabolism
Sepsis-associated acute kidney injury (SA-AKI) is a frequent and severe complication of sepsis and is closely associated with increased mortality. Mitochondrial dysfunction and impaired energy metabolism are important contributors to SA-AKI ...
Roko Mijić Warns AI Growth Could Outpace Human Governance
Roko Mijić posted on X on September 12 that the rapid growth of AI capabilities could bypass human control, arguing that legal and political institutions might fail to steer AI’s expanding abilities in medicine, pensions, goods, and safety toward human benefit.
He sees governance as the condition that turns new capabilities into help for people; new ways of working and finding efficient solutions benefit humans only through rules and institutions that distribute their outputs, which he describes as a fragile link.
In his example, if AI’s ability to find efficient solutions grows about 50% per year, institutions could still treat it as fast economic growth, but at 1,000–10,000% per year AI would have enough optimization power to circumvent human governance, potentially leading to scenarios where AI overthrows the state instead of paying taxes or destroys people instead of treating aging.
He links the need for a slowdown in AI development — referencing an April conversation with David Wood about a contractual pause in the race for general‑purpose AI — to the task of reshaping governance to handle far more disruptive changes, arguing that surviving AI will require both slowing AI and rebuilding institutions.
🔗 Read original →
Roko Mijić posted on X on September 12 that the rapid growth of AI capabilities could bypass human control, arguing that legal and political institutions might fail to steer AI’s expanding abilities in medicine, pensions, goods, and safety toward human benefit.
He sees governance as the condition that turns new capabilities into help for people; new ways of working and finding efficient solutions benefit humans only through rules and institutions that distribute their outputs, which he describes as a fragile link.
In his example, if AI’s ability to find efficient solutions grows about 50% per year, institutions could still treat it as fast economic growth, but at 1,000–10,000% per year AI would have enough optimization power to circumvent human governance, potentially leading to scenarios where AI overthrows the state instead of paying taxes or destroys people instead of treating aging.
He links the need for a slowdown in AI development — referencing an April conversation with David Wood about a contractual pause in the race for general‑purpose AI — to the task of reshaping governance to handle far more disruptive changes, arguing that surviving AI will require both slowing AI and rebuilding institutions.
🔗 Read original →
X (formerly Twitter)
Roko 🐉 (@RokoMijic) on X
The big problem that humanity has with AI is that the legal and political systems that we use to turn work/optimization into utility for us (like medical care, pensions, products to buy, safe stre…
Single amino‑acid swap in CD27 boosts CAR‑T activity against CD70
In a preprint published on September 10, authors changed one amino acid in CD27 – the natural partner of the tumor antigen CD70.
CAR‑T cells are made by giving T lymphocytes a receptor that recognizes a chosen target; here the receptor’s recognition domain is CD27 itself rather than an antibody fragment. A 2025 study (2025 work) showed that a CD27‑CAR construct expanded in mouse blood roughly 80–100‑fold more than antibody‑based CARs in a myeloma model.
To improve CD27, the researchers modeled the CD27:CD70 interface and screened 24 contact residues; the N88A substitution (asparagine → alanine at position 88) emerged as the best candidate from both computational and experimental tests.
In vitro, N88A‑CAR‑T cells killed two AML cell lines faster than the parental CD27‑CAR. In a leukemia mouse model, animals received tumor cells and then 0.5 million CAR‑T cells after four days; tumors stayed below detection limits for the full 85‑day observation in the N88A group, whereas the original CD27‑CAR group had a median survival of 38 days.
In a myeloma model both CD27 versions kept tumors undetectable, but N88A showed greater expansion in mouse blood. Biochemical assays revealed N88A binds CD70 with a slower association rate but a >4‑fold slower dissociation, giving an approximately 2‑fold stronger CD27:CD70 complex; modeling suggests the complex can adopt multiple bound states, consistent with the measured slow off‑rate.
Off‑target screening detected signal only at FCGR3A due to the
🔗 Read original →
In a preprint published on September 10, authors changed one amino acid in CD27 – the natural partner of the tumor antigen CD70.
CAR‑T cells are made by giving T lymphocytes a receptor that recognizes a chosen target; here the receptor’s recognition domain is CD27 itself rather than an antibody fragment. A 2025 study (2025 work) showed that a CD27‑CAR construct expanded in mouse blood roughly 80–100‑fold more than antibody‑based CARs in a myeloma model.
To improve CD27, the researchers modeled the CD27:CD70 interface and screened 24 contact residues; the N88A substitution (asparagine → alanine at position 88) emerged as the best candidate from both computational and experimental tests.
In vitro, N88A‑CAR‑T cells killed two AML cell lines faster than the parental CD27‑CAR. In a leukemia mouse model, animals received tumor cells and then 0.5 million CAR‑T cells after four days; tumors stayed below detection limits for the full 85‑day observation in the N88A group, whereas the original CD27‑CAR group had a median survival of 38 days.
In a myeloma model both CD27 versions kept tumors undetectable, but N88A showed greater expansion in mouse blood. Biochemical assays revealed N88A binds CD70 with a slower association rate but a >4‑fold slower dissociation, giving an approximately 2‑fold stronger CD27:CD70 complex; modeling suggests the complex can adopt multiple bound states, consistent with the measured slow off‑rate.
Off‑target screening detected signal only at FCGR3A due to the
🔗 Read original →
bioRxiv
Deep Learning-based Modeling Enhances Efficacy of Natural Ligand CAR Binders Targeting CD70
CD70 is well-recognized as a promising “pan-cancer” chimeric antigen receptor (CAR) T-cell target. Prior work has shown that a “natural ligand” (NL)-based CAR targeting CD70, employing its physiological interaction partner CD27, may have therapeutic advantages…
PHAROS preprint introduces algorithm to find drug sequences for desired cell states
On September 10 the PHAROS preprint appeared, describing a system that takes the current and desired states of a cell group and searches for an order of drug perturbations that, according to its calculations, brings the first state closer to the second. The approach relies on the STATE model, which is trained to predict how a cell group changes after a drug is applied. Unlike a standard cellular‑response model that predicts the effect of a given drug, PHAROS begins with the initial and target cell states.
The authors frame therapy discovery as a reverse question: “Which interventions are most likely to shift a heterogeneous cell population from its present state to a desired one?” PHAROS applies drugs one at a time; after each step
🔗 Read original →
On September 10 the PHAROS preprint appeared, describing a system that takes the current and desired states of a cell group and searches for an order of drug perturbations that, according to its calculations, brings the first state closer to the second. The approach relies on the STATE model, which is trained to predict how a cell group changes after a drug is applied. Unlike a standard cellular‑response model that predicts the effect of a given drug, PHAROS begins with the initial and target cell states.
The authors frame therapy discovery as a reverse question: “Which interventions are most likely to shift a heterogeneous cell population from its present state to a desired one?” PHAROS applies drugs one at a time; after each step
🔗 Read original →
bioRxiv
PHAROS: turning single-cell perturbation models into target-directed drug-combination screens
Combination therapies are central to cancer treatment, but exhaustive screening is impractical. We introduce PHAROS, a framework that turns a pretrained single-cell perturbation model into a target-directed search engine for drug combinations. PHAROS predicts…
New perspective proposes assay for tissue repair and tumor risk after cancer therapy
On September 11 Adriana Paulina Gudino Reyes published a perspective on restoring normal tissue after cancer treatment. She proposes checking the recovery of damaged tissue together with signs that the intervention might support tumor growth. Oncology metrics track tumor burden, progression and survival; Reyes adds a separate outcome: can damaged normal tissue regain its function. Tissue repair and tumor adaptation may use the same cellular signals. In aged mice, activating the Igf2 gene restored the liver’s regenerative capacity, while blocking the IGF1R protein‑receptor reduced tumor burden in a hepatoblastoma model. In healthy growing mice the same blocker decreased liver size and body mass. One growth pathway participated in both tissue repair and tumor growth under different conditions. Tissue repair engages inflammation, angiogenesis and extracellular‑matrix remodeling; in tumors the same processes occur among malignant, immune and stromal cells. “The same signaling network can support normal‑tissue repair while simultaneously helping the tumor survive, invade or evade immunity.” Reyes recommends moving from simple models to complex ones: first compare normal and tumor human cells before damage, after damage and during recovery; then add stromal and immune cells. Organoids and co‑cultures allow testing their interactions, as do microphysiological systems that replicate tissue functions. In each model she suggests pairing normal‑tissue repair readouts with tumor‑cell proliferation, invasion, angiogenic signaling, genetic integrity and therapy sensitivity. As an example she analyzes stromal cells from Wharton’s jelly – umbilical‑cord tissue – whose properties depend on source, purity, culture conditions, passage number, genetic stability, sterility and traceability from donor to sample. These data let one assess how a specific cell product behaves alongside a particular tumor.
🔗 Read original →
On September 11 Adriana Paulina Gudino Reyes published a perspective on restoring normal tissue after cancer treatment. She proposes checking the recovery of damaged tissue together with signs that the intervention might support tumor growth. Oncology metrics track tumor burden, progression and survival; Reyes adds a separate outcome: can damaged normal tissue regain its function. Tissue repair and tumor adaptation may use the same cellular signals. In aged mice, activating the Igf2 gene restored the liver’s regenerative capacity, while blocking the IGF1R protein‑receptor reduced tumor burden in a hepatoblastoma model. In healthy growing mice the same blocker decreased liver size and body mass. One growth pathway participated in both tissue repair and tumor growth under different conditions. Tissue repair engages inflammation, angiogenesis and extracellular‑matrix remodeling; in tumors the same processes occur among malignant, immune and stromal cells. “The same signaling network can support normal‑tissue repair while simultaneously helping the tumor survive, invade or evade immunity.” Reyes recommends moving from simple models to complex ones: first compare normal and tumor human cells before damage, after damage and during recovery; then add stromal and immune cells. Organoids and co‑cultures allow testing their interactions, as do microphysiological systems that replicate tissue functions. In each model she suggests pairing normal‑tissue repair readouts with tumor‑cell proliferation, invasion, angiogenic signaling, genetic integrity and therapy sensitivity. As an example she analyzes stromal cells from Wharton’s jelly – umbilical‑cord tissue – whose properties depend on source, purity, culture conditions, passage number, genetic stability, sterility and traceability from donor to sample. These data let one assess how a specific cell product behaves alongside a particular tumor.
🔗 Read original →
Researchsquare
An error has occurred
Research Square is a preprint platform that makes research communication faster, fairer, and more useful.
New Neurointerface Restores Speech and Movement via 3D Avatar
This neurointerface helps people with severe paralysis fully restore both nonverbal and verbal communication. While earlier systems could decode either speech or movement in isolation, this development is the first to combine both functions, translating brain signals in real time through a full‑size digital 3D avatar that speaks and reproduces facial expressions and gestures.
It relies on a single high-density ECoG implant that reads the electrical activity of the cerebral cortex. Researchers found that the brain zones responsible for speech and limb movement partly overlap in activity. To prevent interference, engineers built a specialized AI model with parallel decoders that separate and simultaneously process commands for articulation and gesturing (such as a shoulder shrug, head nod, or fist raise).
The neurointerface was successfully tested on three patients who had completely lost the ability to communicate. In dialogue tests the system showed high accuracy of intent recognition, and one participant reached 100% average decoding accuracy for both speech and gestures. This perfect score was maintained across three conversational blocks.
🔗 Read original →
This neurointerface helps people with severe paralysis fully restore both nonverbal and verbal communication. While earlier systems could decode either speech or movement in isolation, this development is the first to combine both functions, translating brain signals in real time through a full‑size digital 3D avatar that speaks and reproduces facial expressions and gestures.
It relies on a single high-density ECoG implant that reads the electrical activity of the cerebral cortex. Researchers found that the brain zones responsible for speech and limb movement partly overlap in activity. To prevent interference, engineers built a specialized AI model with parallel decoders that separate and simultaneously process commands for articulation and gesturing (such as a shoulder shrug, head nod, or fist raise).
The neurointerface was successfully tested on three patients who had completely lost the ability to communicate. In dialogue tests the system showed high accuracy of intent recognition, and one participant reached 100% average decoding accuracy for both speech and gestures. This perfect score was maintained across three conversational blocks.
🔗 Read original →
Nature
Simultaneous speech and gesture decoding for multimodal communication in paralysis
Nature Neuroscience - Brosler et al. develop a brain–computer interface that simultaneously decodes speech and gestures from a single cortical implant to animate a virtual avatar, providing a...
Space Exposure Tests Reveal Cataract Lens Durability on ISS
Scientists sent intraocular lenses used in cataract surgery to the International Space Station to evaluate how artificial lens materials endure the harsh environment of open space. This knowledge is vital for preparing long‑duration missions to the Moon and Mars, where transplantation and on‑site surgical care may become essential because of radiation, injury, and crew aging.
135 lenses were removed from sterile packaging and mounted in special containers on the station’s exterior, where they faced direct vacuum, temperature swings, solar ultraviolet radiation, and a stream of atomic oxygen for six months at three different shielding levels. In parallel, 45 lenses from the same batch were kept in a control container on Earth at room temperature and normal
🔗 Read original →
Scientists sent intraocular lenses used in cataract surgery to the International Space Station to evaluate how artificial lens materials endure the harsh environment of open space. This knowledge is vital for preparing long‑duration missions to the Moon and Mars, where transplantation and on‑site surgical care may become essential because of radiation, injury, and crew aging.
135 lenses were removed from sterile packaging and mounted in special containers on the station’s exterior, where they faced direct vacuum, temperature swings, solar ultraviolet radiation, and a stream of atomic oxygen for six months at three different shielding levels. In parallel, 45 lenses from the same batch were kept in a control container on Earth at room temperature and normal
🔗 Read original →