Longevity InTime: Autonomous AI Institute. Anti-Aging Digital Health Immortality Transhumanist AI Channel
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Blood Age Shift


A recent analysis of 48 DNA segments found that changes in immune cells explained most of the decade-long shift in blood methylation. On August 19, a preprint was published with paired blood samples from 86 elderly participants over ten years. After accounting for the estimated change in immune cell composition, 32.2% of the original rate of shift in the 48-segment metric remained; this residue was not statistically different from zero.

Methylation refers to chemical marks on DNA, which are used to build epigenetic age indicators. However, a blood test always contains a mixture of immune cells, each with their own methylation patterns. If the proportions of these cells change over the years, the average blood signal shifts, even without a similar shift within each cell type. The preprint author took a metric from 48 preselected DNA segments and tracked it in two longitudinal cohorts.

For the Danish cohort of 86 participants, the author estimated changes in the proportions of seven types of immune cells using a separate set of DNA markers and included these changes in the calculation. The rate of shift in the metric dropped to 32.2% of the original, and the model with changing cell composition explained 36.4% of the variance in metric change between participants. Comparing a person to themselves removes their constant features, including their usual blood composition, which can change over ten years.

In a 2024 study, the IntrinClock model was calibrated so that its readings did not change between ten validated types of immune cells. In purified naive CD8+ T cells, its metric still increased with age. Reanalysis of blood should show the shift in immune composition and what remains after such correction separately. Then, one figure does not mix the rearrangement of cells with the change in marks within them, as reported in Nature Aging, July 2026.

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Brain Ultrasound


The SonoMod module attaches to a mouse's head, focusing ultrasound on a brain area while simultaneously recording its response with a miniature camera. On August 18, authors published a preprint on SonoMod, releasing files for assembly, optics, analysis software, and data. Focused ultrasound concentrates sound wave energy in a small brain point.


The device allows for simultaneous stimulation and recording, overcoming previous setup limitations that required head fixation or separate sessions for stimulation and recording. According to the authors, "in neuroscience, tools for intervening in neural circuits and reading their response have traditionally relied on incompatible physics." In SonoMod, light and sound pass through a single module, with a transparent niobate disk converting an electrical signal into ultrasound.


The UCLA Miniscope v4, an open miniature microscope for experiments with freely moving animals, is used with the SonoMod module. Authors tested the device in a series of experiments, first verifying that the camera can see the brain through the module, and then directing ultrasound to the secondary motor cortex (M2). The results were published in a preprint repository and are awaiting review in a neuroscience journal.

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Virtual Gene Knockout

The authors of a preprint compared eight methods that attempt to predict the consequences of gene knockout based on single-cell RNA data. In a test on K562 leukemia cells, the direction predicted by the linear version of CellOracle matched the experiment in 18 out of 44 "transcription factor — gene" pairs. The data on single-cell RNA shows which genes are usually active together, allowing researchers to build a hypothesis about the regulatory network and choose a gene for the next experiment.


The actual gene knockout answers a different question: how will the work of each specific gene change after intervention. The authors tested four transcription factors — proteins that control the work of other genes — and 11 glycolysis genes, the first stage of a cell obtaining energy from glucose. In Perturb-seq, researchers use CRISPRi to suppress the work of a selected gene and then read the RNA of individual cells. The average activity of these 11 genes decreased in all four factors.


The measurements were then compared to the signs of coefficients in the linear version of CellOracle. The sign of the coefficient describes the relationship between genes in the RNA data, and CRISPRi shows their response to intervention. The directions matched in 18 out of 44 cases, as reported in the preprint of August 19.

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AI Model Helps Find Gene

Researchers combined an AI model with data on gene activity in individual blood stem cells, genetic regulator testing, and cell transplantation in mice. They found that the Pbx1 gene is involved in the age-related shift: after transplantation, old cells are less effective at restoring erythrocytes and more likely to produce thrombocyte precursors.

The study, published on August 21 in Science Advances, used the Geneformer AI model to identify the Pbx1 gene as a key regulator of this shift. The model was trained on ten datasets of young and old mouse HSC cells and used to predict which genes, when activated, would make young cells resemble old cells.

The team then tested the prediction in cells by activating 143 genetic regulators associated with blood formation in young HSC cells and tracking the CD48 marker. They found that increased Pbx1 activity slowed the appearance of CD48, and that its activity was higher in old HSC cells.

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Mambbot Project


Molecular biologist Майкл Левин proposes using a series of AI-driven experiments to search for the desired form of living tissue. On 21 августа, he released a lecture on "free lunches," where he describes Mambbot, a collaborative project that uses AI to suggest light, vibration, temperature, or chemical signals to apply to cells to search for a biobot with a specific form and function.


The concept of a "free lunch" refers to the gap between what a system provides and the effort explicitly invested in it through design, selection, or training. According to Levin, this gap defines the next experiment: what property of the system produced the result, and how can it be induced again. This idea grows out of his laboratory's long-standing work at Университете Тафтса on morphogenesis, or how cellular collectives assemble, repair, and change body shape.


In a 2021 article, the authors described ksenobots, mobile constructs made from frog embryo cells. These clusters assembled free cells into new clusters, and an algorithm selected forms that reproduced better. In work on anthrobots, adult human airway cells self-organized into mobile constructs, and in neural cultures, they accelerated the closure of damaged areas. These results provided researchers with a material in which to observe the form and function of cellular collectives after changing conditions.

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Gene Regulator Found


Researchers have discovered that the NHR-49 gene regulator in worms prevents egg cells from maturing without sperm and preserves the organism's reserve. On August 22, the journal Nature Communications published an article on how nutrition is linked to the decision to expend resources on reproduction in the roundworm C. elegans.


When the nhr-49 gene was disrupted, egg cells matured and were released without sperm, causing the organism to lose its yolk and fat reserves, and its lifespan was reduced. In C. elegans, sperm serve as a signal to initiate reproduction, and without this signal, egg cells remain in the oviduct.


A 2025 study by the same group found that sperm-free lines at 25 °C accumulated more fat and lived longer. The current article seeks to identify the molecular mechanism that maintains this waiting state, which was found to be NHR-49, a protein that regulates genes related to nutrition and fat metabolism.

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AI Research Evaluation


Authors propose evaluating AI researchers based on a trail of research decisions. On August 18, nine authors posted a framework for assessing scientific AI agents on ChemRxiv, a preprint repository. The framework's unit is the "discovery episode": a preserved sequence of hypotheses, actions, data, and revisions.


The authors suggest evaluating the entire sequence, including episodes of discovery, which record what was known before the next step, the action chosen by the agent, what was observed, and how the plan changed afterwards. For each step, the episode records the code version, instrument settings, human involvement, and safety rules.


The framework breaks down research work into three connected parts: hypothesis, execution, and interpretation. The authors advise starting with limited tasks, which have a clear goal, can be automatically evaluated, and fit within acceptable time and cost. The separate stages can then be connected into episodes and tested through independent repetition, allowing the evaluator to trace the path from decision to data and the next question, as published in ChemRxiv.

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Brain Immunity Hub

Researchers have discovered structures in the skull's bone marrow where the immune system recognizes antigens, molecular markers from the brain. On August 19, a study in Nature revealed that in mice, these immune cell clusters responded to antigens from the brain. In a glioma brain tumor model, suppressing these clusters weakened the anti-tumor immune response and reduced animal survival.


The brain is surrounded by cerebrospinal fluid, which bathes the brain and spinal cord. Channels between the brain's hard shell and the skull's bone marrow allow this fluid and its dissolved substances to reach neighboring tissue. A 2022 study traced this path and its effect on innate immune cells. The current article's authors investigated whether immune cells in the skull's bone marrow can recognize antigens from the brain.


In the back of the skull's bone marrow, the authors found clusters of B cells, which produce antibodies, T helper cells, and cells that show antigens to T cells. The B cells showed signs of germinal centers, where they are selected and mature to produce antibodies. Comparison with bone marrow from the breastbone and thigh bone, microscopy, and single-cell analysis revealed that such clusters are characteristic of the back of the skull's bone marrow.


In another experiment, mouse neurons were engineered to produce a model protein antigen to track its path. It was detected in the cerebrospinal fluid, brain membranes, and skull bone marrow; immune T and B cells recognizing this protein were activated there. The authors also injected glioma cells with the same antigen either into the brain or under the skin on the mouse's side. When the tumor was inside the brain, the reaction occurred in the skull's bone marrow, while a tumor on the side triggered a response in the inguinal lymph nodes.

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Mouse Lung Repair


Researchers found that disabling genes that transmit tension to the nucleus of connective tissue cells in mice improved lung recovery after injury. On August 18, authors published a preprint on bioRxiv about damaged mouse lungs. When they genetically disabled two genes in fibroblasts, by day 28, this group had less scarring and severely damaged tissue.


Alveoli, the air sacs where blood receives oxygen, are restored by AT2 cells after injury. Nearby alveolar fibroblasts send signals to the epithelium needed for repair. After severe damage, tissue stretching can alter their function for an extended period. To separate the action of stretching from toxic damage, authors partially removed the lung, causing the remaining tissue to stretch more.


In another experiment, they tied off a bronchus of one lobe, reducing stretching in that area. With increased stretching, fibroblasts temporarily lost signs of their normal alveolar state, while reduced stretching preserved them. The researchers had previously shown in a 2024 study that the connection between fibroblasts and epithelium after injury could lead to pathological tissue remodeling; now they checked how physical signals maintained this change. The LINC complex, including Sun1 and Sun2, transmits nuclear tension from intracellular fibers.

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Longevity Support


Aleksey Strigin called on participants in the longevity movement to regularly support strong texts from colleagues. On August 22, the author of the "Economy of Life Extension" channel asked people to spend 10-20 seconds liking or reposting when colleagues ask for help spreading their work, and to ask for such support themselves.

Strigin suggests making mutual recommendations a common practice, so that texts about aging can reach people beyond the usual circle of readers. A strong text can remain in a small channel, where it will be seen mainly by already interested subscribers. A repost shows the text to a different audience: readers trust the person sharing the link and decide whether to read further.

In Facebook, likes, comments, and reposts become signals for the feed that the service selects for each user. The Meta company, which owns Facebook, explains that one of its predictions estimates the likelihood of a repost; this prediction participates in selecting the order of posts. Strigin formulates his stake as: Attention. It is more important than money. It attracts money, talent, and other resources.

A repost associates a person's name with someone else's text. Strigin recalls that he used to be shy about making such requests. The entire community receives a new audience, and each distributor decides whether they are ready to recommend specific material. Mutual support is based on selection. A person first reads the text, then shares what they are willing to be responsible for in front of their subscribers. Repeated recommendations give strong material new audiences, if people continue to choose what they are willing to support with their name.

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Muscle Strength Boost


Researchers found that disabling the P311 gene helped damaged muscles in old mice develop 19% more strength. On August 22, in an article in npj Aging, authors described an experiment on 24-month-old mice: they disabled the P311 gene throughout the body and chemically damaged the tibialis anterior muscle.


Through 28 days after injury, this muscle developed 19% more strength than in similar old mice with P311 enabled. As muscles age, damaged areas often heal with excess collagen, forming scar tissue that hinders fiber function. The authors chose P311 because previous work linked the protein it codes to TGF-β production, a signaling molecule that promotes such tissue formation.


After injury, P311 and TGF-β levels in old muscle increased more than in young muscle. The authors first checked the tissue part of this chain: 14 days after injury, mice without P311 in muscle had less collagen and lower fibrosis-related gene activity. By 28 days, the average cross-sectional area of recovering fibers was 25% larger, and the same tibialis anterior muscle developed 19% more strength.

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Longevity Research Funding


Biogerontologist Matt Kieberlain wrote that exaggerated claims about life extension may undermine trust in data and complicate funding for aging research. Investor Carl Pfleger suggested testing this connection using historical examples. In a detailed post, Kieberlain links gerontology - the study of aging biology - to two conditions: funding for work and data that colleagues are willing to trust.


To move faster, both resources and quality science are needed, he writes. This year, Kieberlain visited the US Congress offices four times, and in three cases, his interlocutors, who had already heard about aging science, associated it with hype and "snake oil". Before discussing new research, he had to return the conversation to the question of whether the data could be trusted.


Kieberlain sees the historical cause of this concern in Sirtris, a biomedicine company that GSK announced it would acquire in 2008 for $720 million. According to Kieberlain, exaggerated expectations around Sirtris long complicated the flow of resources to aging research. Carl Pfleger, an investor in rejuvenation startups, suggests testing this connection using historical examples, citing the 1970s cancer research as a comparable case.

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Epigenetic Clocks

Мартин Йенсен proposed checking epigenetic clocks against health outcomes before measuring therapy effects. He responded to TranslAGE, a new database on epigenetic clock responses to interventions, on August 22. The database, introduced in Nature Medicine on August 21, contains 3,128 samples from 51 longitudinal studies.


The authors calculated 16 epigenetic clocks for each dataset, which estimate age-related changes or mortality risk based on DNA chemical marks. The study allows comparison of how different clocks change after medications, diets, and other interventions. Йенсен suggests comparing these shifts with patient-important outcomes, such as organ function, disease, or mortality.


He uses the COSMOS study as an example, where daily multivitamins did not significantly reduce overall cardiovascular or mortality outcomes over a median of 3.6 years in 21,442 elderly participants. Йенсен proposes an independent test to validate the clocks, where developers make predictions for a set of interventions without knowing the outcomes, and then compare the predictions with the actual data.

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Oliver Barton Releases mTOR Atlas


The mTOR Atlas is a navigator for 322 works on the cellular system affected by rapamycin. Version 1.0.0 was released on August 22 and contains 45 topics, each with a model, intervention, and measured outcome to relate the publication to the question it answers.


The mTOR protein and signaling system, named after it, influences cell growth, protein synthesis, and autophagy through nutrient availability. Experiences in cell culture clarify the mechanism, experiences in animals test it in an organism, and human studies measure the outcome in humans. The Atlas index for each work preserves a link to the original publication, model, intervention, and outcome.


Two markings perform different functions: the pyramid shows how close the data stands to the outcome measured in humans, and levels A–D distinguish types of evidence. In the open upload, 29 level B works were conducted on humans, 84 level C works were conducted on animals, and 205 level D entries comprise mechanistic works and reviews. Such marking helps match the result with the conditions of the experience, as seen in fly experiments where the same dose of rapamycin on different diets changed the sign of the effect on lifespan.


One of the ten pages with open questions is dedicated to mTORC1 and mTORC2, two protein complexes of this system, and separates known results from a "justified hypothesis" about the rapamycin regimen that suppresses mTORC1 and spares mTORC2. To verify this, the Atlas suggests an experiment on mice: comparing lifespan, insulin sensitivity, and mTORC2 activity under different rapamycin regimens, as described in Nature Aging, July 2026.

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Liver Age Tool Released


The authors have released LivAge, an open tool for assessing the age of mouse livers based on gene activity. On August 21, an article about LivAge was published in Aging Cell. The tool receives RNA-seq results and provides an estimate of the mouse liver age in months. The authors have also made the calculation code available.


In aging experiments, it can be difficult to determine whether a diet, medication, or genetic modification affects tissue condition, as the passport age of the control and experimental groups may be the same, and differences in lifespan may take a long time to become apparent. LivAge reduces a large table of gene activity to a single indicator that can be used to compare groups.


The authors trained the model on 432 liver samples from healthy C57BL/6 mice from 23 studies. The age of the animals ranged from one to 30 months, and only control groups without genetic modifications or interventions were included. The algorithm selected 268 genes whose joint activity determines the liver age estimate. The final test was conducted on 134 samples from four other studies that were not used for training and model tuning.

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