3D Culture Rejuvenates Limbal Niche Cells via FOSL1
On September 8, researchers published in Aging Cell that limbal niche cells from human donor tissue were cultured for six days in Matrigel droplets, forming spheroid clusters. Compared with flat culture, these cells divided more frequently and showed fewer signs of replicative senescence.
The limbus is the border between the transparent cornea and the white sclera, and its connective tissue houses limbal niche cells that support the epithelial stem cells renewing the corneal surface. Upon repeated passaging, niche cells divide slower and acquire replicative‑senescence markers, narrowing the available cell stock for further work.
This line of inquiry grew from the group’s 2012 study, in which transferring already‑proliferated cells to three‑dimensional Matrigel restored some stem‑cell‑associated proteins. The new work asks more precisely how a 3D environment alters aging markers and which protein drives this shift.
After 3D culture, the cells contained a higher proportion of dividing cells and a lower proportion of senescence‑positive cells. Single‑cell gene‑expression analysis revealed that two senescence‑associated gene
🔗 Read original →
On September 8, researchers published in Aging Cell that limbal niche cells from human donor tissue were cultured for six days in Matrigel droplets, forming spheroid clusters. Compared with flat culture, these cells divided more frequently and showed fewer signs of replicative senescence.
The limbus is the border between the transparent cornea and the white sclera, and its connective tissue houses limbal niche cells that support the epithelial stem cells renewing the corneal surface. Upon repeated passaging, niche cells divide slower and acquire replicative‑senescence markers, narrowing the available cell stock for further work.
This line of inquiry grew from the group’s 2012 study, in which transferring already‑proliferated cells to three‑dimensional Matrigel restored some stem‑cell‑associated proteins. The new work asks more precisely how a 3D environment alters aging markers and which protein drives this shift.
After 3D culture, the cells contained a higher proportion of dividing cells and a lower proportion of senescence‑positive cells. Single‑cell gene‑expression analysis revealed that two senescence‑associated gene
🔗 Read original →
PubMed Central (PMC)
3D Culture Reverses Limbal Niche Cell Replicative Aging via FOSL1 Upregulation
Limbal niche cells (LNCs) serve as essential regulators of limbal microenvironmental homeostasis and corneal epithelial wound repair, representing a promising therapeutic resource for limbal stem cell deficiency (LSCD). However, their clinical ...
Cystine deficiency triggers metabolic shift in methionine-restricted diets
A preprint posted on bioRxiv, 9 September examined which amino acid—methionine or cystine—activates the metabolic response in methionine‑restricted diets. The researchers divided a standard methionine‑restricted regimen into its two components: reduced methionine and altered cystine levels. In a short‑term test, diets lacking cystine raised FGF21 in mice lacking the cystathionine‑γ‑lyase gene (CTH), while diets with normal cystine kept the hormone near baseline.
Over 10 months, cystine depletion produced divergent outcomes depending on CTH status. In CTH‑deficient mice, a 70 % reduction in cystine (which avoided the ~30 % acute weight loss seen with full removal) curbed age‑related weight gain, preserved lean mass, improved glucose tolerance, and increased grip strength in males. Mice with intact CTH showed stable weight, coordination, grip strength and glucose tolerance on the same diet, but males gained fat mass.
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A preprint posted on bioRxiv, 9 September examined which amino acid—methionine or cystine—activates the metabolic response in methionine‑restricted diets. The researchers divided a standard methionine‑restricted regimen into its two components: reduced methionine and altered cystine levels. In a short‑term test, diets lacking cystine raised FGF21 in mice lacking the cystathionine‑γ‑lyase gene (CTH), while diets with normal cystine kept the hormone near baseline.
Over 10 months, cystine depletion produced divergent outcomes depending on CTH status. In CTH‑deficient mice, a 70 % reduction in cystine (which avoided the ~30 % acute weight loss seen with full removal) curbed age‑related weight gain, preserved lean mass, improved glucose tolerance, and increased grip strength in males. Mice with intact CTH showed stable weight, coordination, grip strength and glucose tolerance on the same diet, but males gained fat mass.
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Brain‑Age Index Links MRI, Mood, Memory and Gut Microbiota in Healthy Adults
A study of 1,462 healthy adults aged 18–65 linked MRI‑derived brain age to memory, mood and gut bacteria. It was published September 9 in the journal eBioMedicine.
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A study of 1,462 healthy adults aged 18–65 linked MRI‑derived brain age to memory, mood and gut bacteria. It was published September 9 in the journal eBioMedicine.
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eBioMedicine
Brain-gut crosstalk associated with brain ageing in young and mid-life adults: a multicohort cross-sectional study
A connectivity-derived BAI captures reproducible variability in early brain ageing
and links large-scale brain network organisation to gut-derived biological signatures.
These findings suggest that BAI captures individual variability associated with brain…
and links large-scale brain network organisation to gut-derived biological signatures.
These findings suggest that BAI captures individual variability associated with brain…
Protein proximity map guides dual‑target antibody design
On September 9, 2026, Nature, September 9, 2026 published a method to select two targets for a single anticancer molecule based on their proximity on the tumor cell surface. The authors chose the EGFR–CDCP1 pair and tested an antibody that binds both proteins and carries a toxic payload.
To map proximity, they attached photosensitive labels to 12 surface receptors, left chemical traces on nearby proteins, and used mass spectrometry to read the traces, generating 248 proximity maps across 28 tumor cell systems. The MetaMap algorithm matched the maps and highlighted CDCP1 as a frequent EGFR neighbor in tumors but not in normal epithelial or mesenchymal cells.
The finding was validated with reciprocal labeling, an additional series of 38 CDCP1 maps in 19 tumor systems, and co‑isolated EGFR protein analysis, showing that proximity strength varied independently of each protein’s abundance.
Researchers then built a bispecific antibody with one arm binding EGFR, the other binding CDCP1, and a cytotoxic payload; EGFR binding was weakened to favor simultaneous engagement of both receptors. In cell assays the bispecific antibody entered tumor cells more effectively than monospecific antibodies, correlating with dual receptor engagement, while uptake in primary epithelial cells was much lower.
In mice bearing SW48 xenografts, a dose of 1 mg/kg of the bispecific antibody gave complete tumor growth inhibition, whereas an EGFR‑only antibody achieved only 43% inhibition (each group n=8). When each mouse carried two tumors—wild‑type SW48 and a CDCP1‑low variant—a dose of 3 mg/kg produced 97% inhibition in the wild‑type tumor and 46% in the CDCP1‑low tumor, underscoring CDCP1’s role in payload delivery.
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On September 9, 2026, Nature, September 9, 2026 published a method to select two targets for a single anticancer molecule based on their proximity on the tumor cell surface. The authors chose the EGFR–CDCP1 pair and tested an antibody that binds both proteins and carries a toxic payload.
To map proximity, they attached photosensitive labels to 12 surface receptors, left chemical traces on nearby proteins, and used mass spectrometry to read the traces, generating 248 proximity maps across 28 tumor cell systems. The MetaMap algorithm matched the maps and highlighted CDCP1 as a frequent EGFR neighbor in tumors but not in normal epithelial or mesenchymal cells.
The finding was validated with reciprocal labeling, an additional series of 38 CDCP1 maps in 19 tumor systems, and co‑isolated EGFR protein analysis, showing that proximity strength varied independently of each protein’s abundance.
Researchers then built a bispecific antibody with one arm binding EGFR, the other binding CDCP1, and a cytotoxic payload; EGFR binding was weakened to favor simultaneous engagement of both receptors. In cell assays the bispecific antibody entered tumor cells more effectively than monospecific antibodies, correlating with dual receptor engagement, while uptake in primary epithelial cells was much lower.
In mice bearing SW48 xenografts, a dose of 1 mg/kg of the bispecific antibody gave complete tumor growth inhibition, whereas an EGFR‑only antibody achieved only 43% inhibition (each group n=8). When each mouse carried two tumors—wild‑type SW48 and a CDCP1‑low variant—a dose of 3 mg/kg produced 97% inhibition in the wild‑type tumor and 46% in the CDCP1‑low tumor, underscoring CDCP1’s role in payload delivery.
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Nature
Proximity-guided graph learning reveals tumour-associated proximity antigens
Nature - A proximity-mapping atlas defines tumour-associated proximity antigens, revealing disease-associated membrane spatial communities, and identifies EGFR–CDCP1 as a co-target pair that...
Allogenetics Secures €3.8 Million for Gene‑Edited Donor Lung Trial
On September 9, German biotech Allogenetics closed a €3.8 million financing round. The funds will support preclinical work needed for an IND filing for its ALG-115 program, which aims to treat donor lungs with gene therapy before transplantation.
In ALG-115, donor lungs are kept alive on a perfusion device and receive gene therapy that lowers MHC I and II expression on the organ’s cells. By reducing these molecules, the recipient’s immune system is less likely to recognize the transplant as foreign, potentially decreasing rejection risk while still preserving the lung’s ability to fight infections.
As transplant surgeon Jeffrey Platt of the University of Michigan Medical School explained, “When the intervention is directed at the donor organ, the recipient’s immune system can be preserved.”
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On September 9, German biotech Allogenetics closed a €3.8 million financing round. The funds will support preclinical work needed for an IND filing for its ALG-115 program, which aims to treat donor lungs with gene therapy before transplantation.
In ALG-115, donor lungs are kept alive on a perfusion device and receive gene therapy that lowers MHC I and II expression on the organ’s cells. By reducing these molecules, the recipient’s immune system is less likely to recognize the transplant as foreign, potentially decreasing rejection risk while still preserving the lung’s ability to fight infections.
As transplant surgeon Jeffrey Platt of the University of Michigan Medical School explained, “When the intervention is directed at the donor organ, the recipient’s immune system can be preserved.”
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Science Translational Medicine
Knockdown of swine leukocyte antigen expression in porcine lung transplants enables graft survival without immunosuppression
Down-regulation of swine leukocyte antigen expression supports graft survival after allogeneic lung transplantation in minipigs.
Bacterial B12 Extends Worm Lifespan via Mitochondrial Renewal When rict-1 Is Off
On 14 September 2026, Nature Communications, 14 September 2026 reported that bacterial vitamin B12 extends the lifespan of *Caenorhabditis elegans* when the rict-1 gene is knocked out, by promoting mitochondrial renewal.
Worms obtain B12 from the bacteria they eat; a diet rich in the HT115 strain increases both longevity and osmotic stress resistance in rict-1 mutants, and the same effect occurs with B12 supplementation of the standard OP50 feed, but only when sufficient methionine is present.
Earlier work linked rict-1 to diet and lifespan (2009 study), and the same lab found a B12‑dependent longevity path in flr-4 mutants (2022 study); this paper pinpoints the exact pathway connecting B12 to the rict-1 effect.
The researchers disabled B12‑dependent enzymes involved in methionine and propionate metabolism, which raised succinate levels; blocking succinate formation reduced stress resistance and lifespan, while adding succinic acid restored them, identifying succinate as a crucial link.
Succinate then drives mitochondrial fission via DRP-1; inhibiting DRP-1 lowered stress resistance and lifespan, and enhanced mitophagy—detected with a fluorescent sensor—required pink-1 and pdr-1; loss of those genes diminished mitophagy, stress resistance, and the lifespan advantage of rict-1 mutants.
Norm
🔗 Read original →
On 14 September 2026, Nature Communications, 14 September 2026 reported that bacterial vitamin B12 extends the lifespan of *Caenorhabditis elegans* when the rict-1 gene is knocked out, by promoting mitochondrial renewal.
Worms obtain B12 from the bacteria they eat; a diet rich in the HT115 strain increases both longevity and osmotic stress resistance in rict-1 mutants, and the same effect occurs with B12 supplementation of the standard OP50 feed, but only when sufficient methionine is present.
Earlier work linked rict-1 to diet and lifespan (2009 study), and the same lab found a B12‑dependent longevity path in flr-4 mutants (2022 study); this paper pinpoints the exact pathway connecting B12 to the rict-1 effect.
The researchers disabled B12‑dependent enzymes involved in methionine and propionate metabolism, which raised succinate levels; blocking succinate formation reduced stress resistance and lifespan, while adding succinic acid restored them, identifying succinate as a crucial link.
Succinate then drives mitochondrial fission via DRP-1; inhibiting DRP-1 lowered stress resistance and lifespan, and enhanced mitophagy—detected with a fluorescent sensor—required pink-1 and pdr-1; loss of those genes diminished mitophagy, stress resistance, and the lifespan advantage of rict-1 mutants.
Norm
🔗 Read original →
Nature
RICTOR regulates an interspecies crosstalk that influences longevity through a methionine cycle-mitophagy axis
Nature Communications - Physiological traits are modulated in response to diet. Here the authors show that RICTOR restrains host responses to vitamin B12 in C. elegans by modulating organellar...
Preprint links iPSC‑derived vascular cells to improved blood flow in mice
A preprint published September 9 combined 68 preclinical studies of vascular cells made from induced pluripotent stem cells. In the primary analysis of 51 works with 114 comparisons, tissue blood flow after cell therapy was on average 1.96‑fold higher than in control groups.
Limb ischemia occurs when blood supply to tissues is inadequate, causing oxygen shortage. In the lab, iPSCs can be turned into various specialized cells, including the endothelial lining of blood vessels. Researchers injected these cells into mice with hindered limb
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A preprint published September 9 combined 68 preclinical studies of vascular cells made from induced pluripotent stem cells. In the primary analysis of 51 works with 114 comparisons, tissue blood flow after cell therapy was on average 1.96‑fold higher than in control groups.
Limb ischemia occurs when blood supply to tissues is inadequate, causing oxygen shortage. In the lab, iPSCs can be turned into various specialized cells, including the endothelial lining of blood vessels. Researchers injected these cells into mice with hindered limb
🔗 Read original →
bioRxiv
Evaluation of the Translational Readiness of Pluripotent Stem Cell–Derived Vascular Cell Therapy for Limb Ischemia: A Systematic…
Background For the first time, pluripotent stem cell (PSC)-derived endothelial cells were administered to a human for peripheral artery disease (PAD), in August 2026. This translation is based on a large preclinical literature claiming that donor cells build…
Heart lymphatic vessels decay before fibrosis in aging mice
In old mice, heart lymphatic vessels thin before scarring and thickening; the cause is the nuclear form of
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In old mice, heart lymphatic vessels thin before scarring and thickening; the cause is the nuclear form of
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Nature
Age-associated loss of lymphatic vessels promotes cardiac inflammation
Nature Cardiovascular Research - Wagner et al. reveal that age-related impairment of lymphatic integrity is driven by increased nuclear interleukin-33 expression in lymphatic endothelial cells and...
AI drug‑discovery models Boltz‑2 and Nesso‑1 falter on rare protein families, simple method wins
On September 13, independent researchers published the MIRAGE preprint benchmark, showing that on proteins scarcely represented in public databases both Boltz‑2 and Nesso‑1 lose to a simpler, cheaper method.
Boltz‑2 was released in June 2025 by MIT and Recursion (Nasdaq: RXRX), with a press release claiming it approaches the accuracy of costly physics‑based binding‑energy calculations while being up to 1,000 times faster. Recursion’s scientific director Nadjat Khan stressed that early‑molecule selection is a fundamental drug‑discovery challenge.
Over a year later Recursion’s Valence Labs released Nesso‑1, which Khan said matches or exceeds Boltz‑2 on public benchmarks; the MIRAGE preprint was used to test this claim.
Suspicions that the models memorize protein families rather than learning binding physics were examined across the full spectrum of family representation. Accuracy of Boltz‑2 and Nesso‑1 rose with family representation, while controls deprived of family data showed no improvement.
Even after removing cases where the model could have seen the exact protein before, the effect persisted, indicating recognition of whole families rather than single entries. On families rarely seen, a simple random forest without family data outperformed both neural nets.
To test on a truly low‑representation target, the authors used binding data released in May 2026; neither Boltz‑2 nor Nesso‑1 nor classical docking tools could reliably beat the baseline of predicting activity from molecular mass alone. Boltz‑2 fell below this baseline, Nesso‑1 was barely above but the difference was deemed statistically insignificant.
Adding evolutionary alignment as an input boosted Boltz‑2’s accuracy on unfamiliar families from 2% to 46%, while performance on familiar families remained unchanged; the released model does not receive this signal.
The MIRAGE authors conclude that selecting models by average accuracy favors familiarity with already solved protein families, and advise checking how well a target’s family is represented in the training data before trusting predictions.
🔗 Read original →
On September 13, independent researchers published the MIRAGE preprint benchmark, showing that on proteins scarcely represented in public databases both Boltz‑2 and Nesso‑1 lose to a simpler, cheaper method.
Boltz‑2 was released in June 2025 by MIT and Recursion (Nasdaq: RXRX), with a press release claiming it approaches the accuracy of costly physics‑based binding‑energy calculations while being up to 1,000 times faster. Recursion’s scientific director Nadjat Khan stressed that early‑molecule selection is a fundamental drug‑discovery challenge.
Over a year later Recursion’s Valence Labs released Nesso‑1, which Khan said matches or exceeds Boltz‑2 on public benchmarks; the MIRAGE preprint was used to test this claim.
Suspicions that the models memorize protein families rather than learning binding physics were examined across the full spectrum of family representation. Accuracy of Boltz‑2 and Nesso‑1 rose with family representation, while controls deprived of family data showed no improvement.
Even after removing cases where the model could have seen the exact protein before, the effect persisted, indicating recognition of whole families rather than single entries. On families rarely seen, a simple random forest without family data outperformed both neural nets.
To test on a truly low‑representation target, the authors used binding data released in May 2026; neither Boltz‑2 nor Nesso‑1 nor classical docking tools could reliably beat the baseline of predicting activity from molecular mass alone. Boltz‑2 fell below this baseline, Nesso‑1 was barely above but the difference was deemed statistically insignificant.
Adding evolutionary alignment as an input boosted Boltz‑2’s accuracy on unfamiliar families from 2% to 46%, while performance on familiar families remained unchanged; the released model does not receive this signal.
The MIRAGE authors conclude that selecting models by average accuracy favors familiarity with already solved protein families, and advise checking how well a target’s family is represented in the training data before trusting predictions.
🔗 Read original →
bioRxiv
Boltz-2: Towards Accurate and Efficient Binding Affinity Prediction
Accurately modeling biomolecular interactions is a central challenge in modern biology. While recent advances, such as AlphaFold3 and Boltz-1, have substantially improved our ability to predict biomolecular complex structures, these models still fall short…
Insilico Launches Longevity Vaccines Program to Reprogram T‑Cells In Vivo
On September 15 Insilico Medicine announced its Longevity Vaccines program, which uses cyclic RNA in a lipid nanoparticle to temporarily teach a patient’s T‑cells to hunt and destroy senescent cells, activated fibroblasts and autoreactive lymphocytes. The first target is senescent immune cells, whose accumulation weakens vaccine responses and raises susceptibility to infections and cancer with age.
The approach mirrors CAR‑T therapy: an RNA‑encoded receptor turns the patient’s own T‑cells into carriers that attack the chosen culprit cells, then the RNA degrades,
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On September 15 Insilico Medicine announced its Longevity Vaccines program, which uses cyclic RNA in a lipid nanoparticle to temporarily teach a patient’s T‑cells to hunt and destroy senescent cells, activated fibroblasts and autoreactive lymphocytes. The first target is senescent immune cells, whose accumulation weakens vaccine responses and raises susceptibility to infections and cancer with age.
The approach mirrors CAR‑T therapy: an RNA‑encoded receptor turns the patient’s own T‑cells into carriers that attack the chosen culprit cells, then the RNA degrades,
🔗 Read original →
Insilico
Insilico Launches AI-driven Longevity Vaccines Research for Aging-related Diseases and Human Longevity
The program applies generative AI and programmable RNA medicine to design single-administration, self-limiting in vivo cell therapies that clear the earliest culprit cells of age-related disease.
LSD1 enzyme prolongs DNA‑damage signal, driving cellular senescence
On 15 September, the Journal of Clinical Investigation published a study from the Mayo Clinic and Tongji University showing that the enzyme LSD1 builds up in aged mouse kidneys, heart, liver and in artificially aged cells because the cell cannot degrade it efficiently. LSD1 removes a methyl group from the ATM protein at residue 3016, preventing ATM from turning off after DNA repair and keeping the damage signal active.
When ATM stays active, the phosphatase WIP1 cannot bind well to the unmethylated site, so the DNA‑damage alarm persists longer than needed. This prolonged signal pushes the cell into a stable growth arrest — senescence — where it secretes harmful factors that damage surrounding tissues.
Normally, LSD1 is cleared by autophagy through binding to LC3 and Beclin1; with age autophagy weakens, the LSD1‑LC3/Beclin1 link breaks, and LSD1 accumulates in the nucleus where ATM resides. Enhancing autophagy with rapamycin lowers LSD1 levels even in old organs, while blocking autophagy raises LSD1 even in young ones.
Senolytic drugs that eliminate senescent cells also reduced LSD1 and senescence markers in the kidneys, heart and liver of old mice; a regimen of dasatinib + quercetin restored the kidney‑protective protein Klotho and lessened fibrosis.
The LSD1 inhibitor ORY-1001 (iadademstat), already tested in humans for acute myeloid leukemia, myelodysplastic syndrome and small‑cell lung cancer, decreased DNA damage and aging signs in the kidneys, heart and liver of irradiated and aged mice, and protected them from radiation‑induced hair graying. These effects on aging have been demonstrated only in mice and cells so far.
Together, the work links two hallmarks of aging — persistent DNA‑damage signaling and declining cellular cleanup — to a single switch on ATM: LSD1 does not decide whether the alarm sounds, but how long it lasts, determining whether a cell returns to division or becomes stuck in senescence.
🔗 Read original →
On 15 September, the Journal of Clinical Investigation published a study from the Mayo Clinic and Tongji University showing that the enzyme LSD1 builds up in aged mouse kidneys, heart, liver and in artificially aged cells because the cell cannot degrade it efficiently. LSD1 removes a methyl group from the ATM protein at residue 3016, preventing ATM from turning off after DNA repair and keeping the damage signal active.
When ATM stays active, the phosphatase WIP1 cannot bind well to the unmethylated site, so the DNA‑damage alarm persists longer than needed. This prolonged signal pushes the cell into a stable growth arrest — senescence — where it secretes harmful factors that damage surrounding tissues.
Normally, LSD1 is cleared by autophagy through binding to LC3 and Beclin1; with age autophagy weakens, the LSD1‑LC3/Beclin1 link breaks, and LSD1 accumulates in the nucleus where ATM resides. Enhancing autophagy with rapamycin lowers LSD1 levels even in old organs, while blocking autophagy raises LSD1 even in young ones.
Senolytic drugs that eliminate senescent cells also reduced LSD1 and senescence markers in the kidneys, heart and liver of old mice; a regimen of dasatinib + quercetin restored the kidney‑protective protein Klotho and lessened fibrosis.
The LSD1 inhibitor ORY-1001 (iadademstat), already tested in humans for acute myeloid leukemia, myelodysplastic syndrome and small‑cell lung cancer, decreased DNA damage and aging signs in the kidneys, heart and liver of irradiated and aged mice, and protected them from radiation‑induced hair graying. These effects on aging have been demonstrated only in mice and cells so far.
Together, the work links two hallmarks of aging — persistent DNA‑damage signaling and declining cellular cleanup — to a single switch on ATM: LSD1 does not decide whether the alarm sounds, but how long it lasts, determining whether a cell returns to division or becomes stuck in senescence.
🔗 Read original →
PubMed Central (PMC)
LSD1-mediated demethylation of the DNA damage response factor ATM promotes senescence and organ aging
Aging occurs heterogeneously across organs, leading to progressive tissue dysfunction. Cellular senescence is a stress response triggered by age-associated insults, yet the mechanisms regulating senescence and organ aging remain incompletely ...
Loss of liver protein hepatopoietin accelerates aging and impairs regeneration in old mice
The liver‑secreted protein hepatopoietin (also known as FGL1) declines with age in both mice and humans, and its loss worsens outcomes after partial liver removal in aged animals. Mice lacking the hepatopoietin gene show higher mortality and poorer liver regeneration following surgery compared with normal old and young mice.
When two‑thirds of the liver were removed, 87% of normal old mice survived to day seven, whereas only 40% of hepatopoietin‑deficient mice lived; the deficient mice restored just half of the lost liver mass versus 64% in controls. Young mice showed little effect from the protein loss because compensatory pathways maintain AMPK activity.
Hepatopoietin binds the hepatocyte receptor ANXA2 and triggers the ERK → p90RSK → LKB1 cascade that activates AMPK, the cell’s main energy sensor. Without hepatopoietin AMPK is weakened, mTOR becomes hyperactive, and autophagy and cell division are blocked, contributing to the aged liver’s poor regenerative capacity.
Direct activation of AMPK with the drug AICAR, or pretreatment with recombinant hepatopoietin, restored regeneration and improved survival in the deficient mice; hepatopoietin was nontoxic even at a dose 20 times the effective level. These treatments also enhanced liver mass recovery in normal old mice.
Although hepatopoietin/FGL1 is better known in oncology for binding the immune checkpoint LAG‑3, the study shows that age‑related liver decline can be countered either by boosting AMPK directly or by replenishing hepatopoietin. Pharmacologic AMPK activation (e.g., ATX‑304 from Cambrian Bio) has already reduced liver fat in humans, though similar agents have carried side‑effect risks such as cardiac enlargement.
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The liver‑secreted protein hepatopoietin (also known as FGL1) declines with age in both mice and humans, and its loss worsens outcomes after partial liver removal in aged animals. Mice lacking the hepatopoietin gene show higher mortality and poorer liver regeneration following surgery compared with normal old and young mice.
When two‑thirds of the liver were removed, 87% of normal old mice survived to day seven, whereas only 40% of hepatopoietin‑deficient mice lived; the deficient mice restored just half of the lost liver mass versus 64% in controls. Young mice showed little effect from the protein loss because compensatory pathways maintain AMPK activity.
Hepatopoietin binds the hepatocyte receptor ANXA2 and triggers the ERK → p90RSK → LKB1 cascade that activates AMPK, the cell’s main energy sensor. Without hepatopoietin AMPK is weakened, mTOR becomes hyperactive, and autophagy and cell division are blocked, contributing to the aged liver’s poor regenerative capacity.
Direct activation of AMPK with the drug AICAR, or pretreatment with recombinant hepatopoietin, restored regeneration and improved survival in the deficient mice; hepatopoietin was nontoxic even at a dose 20 times the effective level. These treatments also enhanced liver mass recovery in normal old mice.
Although hepatopoietin/FGL1 is better known in oncology for binding the immune checkpoint LAG‑3, the study shows that age‑related liver decline can be countered either by boosting AMPK directly or by replenishing hepatopoietin. Pharmacologic AMPK activation (e.g., ATX‑304 from Cambrian Bio) has already reduced liver fat in humans, though similar agents have carried side‑effect risks such as cardiac enlargement.
🔗 Read original →
Nature
Hepassocin prevents age-related liver senescence and facilitates liver regeneration by activating AMPK
Signal Transduction and Targeted Therapy - Hepassocin prevents age-related liver senescence and facilitates liver regeneration by activating AMPK
Restoring IGFBP5 in aged dental stem cells reverses senescence and boosts bone repair
Researchers from Sichuan University reported on 15 September in International Journal of Oral Science that dental follicle stem cells lose the protein IGFBP5 with age, and restoring IGFBP5 suppresses the aging marker WNT5B, thereby reversing cellular senescence and improving periodontal healing in rats.
By comparing RNA from young cells and cells aged by oxidative stress or repeated divisions, the team identified IGFBP5 as a sharply downregulated factor — its expression fell 69‑fold in the division‑based aging model — despite its known role in promoting osteogenic differentiation.
Functional tests showed that knocking down IGFBP5 in young cells triggered senescence and reduced bone formation, whereas reintroducing IGFBP5 in aged cells cleared senescence markers and restored osteogenic capacity; this effect was mediated by decreased WNT5B and downstream c‑Jun activity, while the canonical Wnt pathway remained unchanged.
When direct IGFBP5 rescue was ineffective in severely aged cells, administering an antibody against WNT5B partially alleviated senescence, confirming the causal axis.
For therapeutic application, the scientists embedded IGFBP5‑rejuvenated cells in a hydrogel containing hydroxyapatite hydrogel nanoparticles; implantation into rat periodontitis lesions yielded greater bone density and volume, lower inflammation, richer collagen, and heightened expression of osteogenic genes compared with empty hydrogel or hydrogel with untreated cells.
Treated tissue also showed reduced GLB1 (a senescence marker), elevated IGFBP5, and lowered WNT5B, mirroring the in‑vitro findings; the authors conclude that preconditioning aged stem cells before implantation — rather than transplanting naïve cells — markedly enhances periodontal bone regeneration and may benefit other age‑related bone disorders.
🔗 Read original →
Researchers from Sichuan University reported on 15 September in International Journal of Oral Science that dental follicle stem cells lose the protein IGFBP5 with age, and restoring IGFBP5 suppresses the aging marker WNT5B, thereby reversing cellular senescence and improving periodontal healing in rats.
By comparing RNA from young cells and cells aged by oxidative stress or repeated divisions, the team identified IGFBP5 as a sharply downregulated factor — its expression fell 69‑fold in the division‑based aging model — despite its known role in promoting osteogenic differentiation.
Functional tests showed that knocking down IGFBP5 in young cells triggered senescence and reduced bone formation, whereas reintroducing IGFBP5 in aged cells cleared senescence markers and restored osteogenic capacity; this effect was mediated by decreased WNT5B and downstream c‑Jun activity, while the canonical Wnt pathway remained unchanged.
When direct IGFBP5 rescue was ineffective in severely aged cells, administering an antibody against WNT5B partially alleviated senescence, confirming the causal axis.
For therapeutic application, the scientists embedded IGFBP5‑rejuvenated cells in a hydrogel containing hydroxyapatite hydrogel nanoparticles; implantation into rat periodontitis lesions yielded greater bone density and volume, lower inflammation, richer collagen, and heightened expression of osteogenic genes compared with empty hydrogel or hydrogel with untreated cells.
Treated tissue also showed reduced GLB1 (a senescence marker), elevated IGFBP5, and lowered WNT5B, mirroring the in‑vitro findings; the authors conclude that preconditioning aged stem cells before implantation — rather than transplanting naïve cells — markedly enhances periodontal bone regeneration and may benefit other age‑related bone disorders.
🔗 Read original →
Nature
Impact of allogeneic dental pulp stem cell injection on tissue regeneration in periodontitis: a multicenter randomized clinical…
Signal Transduction and Targeted Therapy - Impact of allogeneic dental pulp stem cell injection on tissue regeneration in periodontitis: a multicenter randomized clinical trial
Clearing senescent p16‑positive cells improves heart relaxation in aged mice
In old mice, genetic removal of p16‑positive senescent cells reduced ventricular wall thickening and fibrosis and restored normal diastolic relaxation. The study appeared 14 September in Experimental Physiology from the Montreal Heart Institute.
Using the INK‑ATTAC line, the drug AP20187 was given from 12 to 18 months of age to kill p16‑positive cells; untreated mice showed increased left‑ventricular wall thickness, fibrosis, and slowed relaxation over six months, while clearance attenuated all three changes.
A p16‑positive cell is senescent: it has stopped dividing but remains alive and secretes factors that damage nearby tissue. INK‑ATTAC cells carry a fluorescent switch so that AP20187 eliminates only the labeled cells, allowing precise tracking; with age the p16‑positive fraction rises in all heart cell types, especially immune cells and fibroblasts.
Six months of AP20187 versus placebo left treated mice with little increase in left‑ventricular mass or wall thickness, whereas controls showed significant growth; isovolumic relaxation time stayed youthful in treated mice and rose in controls. Ejection fraction and contractility were unchanged, indicating a selective effect on relaxation, not contraction.
Flow cytometry and staining revealed that the drug lowered the p16‑positive fraction in fibroblasts and cardiomyocytes but not in vascular cells, accompanied by decreased Myh7 hypertrophy gene activity and collagen content, confirmed by both tissue staining and biochemical assays.
In an ex‑vivo experiment, hydrogen peroxide‑induced senescent fibroblasts placed near healthy cardiomyocytes across a permeable membrane triggered hypertrophy genes in the muscle within two days, demonstrating a paracrine effect; although there is a theoretical risk of losing cardiomyocytes, clearance was accompanied by functional improvement, not tissue loss.
After myocardial infarction in middle‑aged mice, Navitoclax reduced scar area to 13.6% versus 18.9% in controls; experiments used males and systemic clearance, and the INK‑ATTAC model originates from the 2016 work linking p16‑positive accumulation to shortened mouse lifespan.
Earlier studies by senior author Stanley Nattel on atria and rhythm showed that in a 2025 human trial the senolytic quercetin lowered post‑operative atrial fibrillation incidence by >75%; the current study extends this logic to the ventricle and diastolic dysfunction, a common cause of heart failure in older people.
🔗 Read original →
In old mice, genetic removal of p16‑positive senescent cells reduced ventricular wall thickening and fibrosis and restored normal diastolic relaxation. The study appeared 14 September in Experimental Physiology from the Montreal Heart Institute.
Using the INK‑ATTAC line, the drug AP20187 was given from 12 to 18 months of age to kill p16‑positive cells; untreated mice showed increased left‑ventricular wall thickness, fibrosis, and slowed relaxation over six months, while clearance attenuated all three changes.
A p16‑positive cell is senescent: it has stopped dividing but remains alive and secretes factors that damage nearby tissue. INK‑ATTAC cells carry a fluorescent switch so that AP20187 eliminates only the labeled cells, allowing precise tracking; with age the p16‑positive fraction rises in all heart cell types, especially immune cells and fibroblasts.
Six months of AP20187 versus placebo left treated mice with little increase in left‑ventricular mass or wall thickness, whereas controls showed significant growth; isovolumic relaxation time stayed youthful in treated mice and rose in controls. Ejection fraction and contractility were unchanged, indicating a selective effect on relaxation, not contraction.
Flow cytometry and staining revealed that the drug lowered the p16‑positive fraction in fibroblasts and cardiomyocytes but not in vascular cells, accompanied by decreased Myh7 hypertrophy gene activity and collagen content, confirmed by both tissue staining and biochemical assays.
In an ex‑vivo experiment, hydrogen peroxide‑induced senescent fibroblasts placed near healthy cardiomyocytes across a permeable membrane triggered hypertrophy genes in the muscle within two days, demonstrating a paracrine effect; although there is a theoretical risk of losing cardiomyocytes, clearance was accompanied by functional improvement, not tissue loss.
After myocardial infarction in middle‑aged mice, Navitoclax reduced scar area to 13.6% versus 18.9% in controls; experiments used males and systemic clearance, and the INK‑ATTAC model originates from the 2016 work linking p16‑positive accumulation to shortened mouse lifespan.
Earlier studies by senior author Stanley Nattel on atria and rhythm showed that in a 2025 human trial the senolytic quercetin lowered post‑operative atrial fibrillation incidence by >75%; the current study extends this logic to the ventricle and diastolic dysfunction, a common cause of heart failure in older people.
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PubMed Central (PMC)
Clearance of p16‐positive cardiac cells improves age‐related cardiac remodeling in mice
Senescent cells are characterized by expression of markers like p16 and secretion of profibrotic and proinflammatory factors. The role of cellular senescence in age‐related cardiac remodeling and dysfunction is incompletely understood. This study ...
U‑shaped DNA methylation mirrors mortality, yielding new aging clocks
Препринт МГУ, 14 сентября
Researchers from Moscow State University compared blood DNA methylation across 16 chronic human diseases with aging and mortality data from 42 mammalian species. They sought to see whether epigenetic changes follow the same U‑shaped mortality curve observed across the lifespan.
In the four species with infant methylation data — human, cat, zebra, and dolphin — between a quarter and half of significant methylation sites changed with age in a U‑shaped pattern. Specifically, 24.8% of sites in humans, 43.2% in zebras, 49.8% in dolphins, and 50.2% in cats mirrored this curve, echoing the non‑
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Препринт МГУ, 14 сентября
Researchers from Moscow State University compared blood DNA methylation across 16 chronic human diseases with aging and mortality data from 42 mammalian species. They sought to see whether epigenetic changes follow the same U‑shaped mortality curve observed across the lifespan.
In the four species with infant methylation data — human, cat, zebra, and dolphin — between a quarter and half of significant methylation sites changed with age in a U‑shaped pattern. Specifically, 24.8% of sites in humans, 43.2% in zebras, 49.8% in dolphins, and 50.2% in cats mirrored this curve, echoing the non‑
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Did you know that racket sports are considered the most life-extending? Research shows they combine interval effort, coordination, and social interaction — key drivers of longevity.
That’s why Longevity InTime is investing in pickleball: the most accessible racket sport for all ages. Easy to start, fun to play, and built for community.
Here’s what we’re starting with:
🔥 Preparing the selection of the best of the best in pickleball!
🎯 Goal: to send 4 athletes from Russia to the European Open in Turkey.
🏆 Categories: men's and women's doubles.
📊 Format: We'll announce it tomorrow.
This is just the beginning.
What comes next will be a game-changer for 190 nations.
We unite the best in the world. Become part of Pickleball Partners right now:
https://t.me/PickleballPartners
That’s why Longevity InTime is investing in pickleball: the most accessible racket sport for all ages. Easy to start, fun to play, and built for community.
Here’s what we’re starting with:
🔥 Preparing the selection of the best of the best in pickleball!
🎯 Goal: to send 4 athletes from Russia to the European Open in Turkey.
🏆 Categories: men's and women's doubles.
📊 Format: We'll announce it tomorrow.
This is just the beginning.
What comes next will be a game-changer for 190 nations.
We unite the best in the world. Become part of Pickleball Partners right now:
https://t.me/PickleballPartners
Telegram
Pickleball Partners
Uniting the best in pickleball worldwide. Forming national teams, hosting international tournaments, supporting athletes, and organizing longevity forums.
The sports arm of @LongevityInTime.
Collaboration:
@InTimeDigitizeMeToLive120
The sports arm of @LongevityInTime.
Collaboration:
@InTimeDigitizeMeToLive120
Longevity InTime: Autonomous AI Institute. Anti-Aging Digital Health Immortality Transhumanist AI Channel pinned «Did you know that racket sports are considered the most life-extending? Research shows they combine interval effort, coordination, and social interaction — key drivers of longevity. That’s why Longevity InTime is investing in pickleball: the most accessible…»
Adult Drosophila thigh muscle rebuilds destroyed myofibrils in a week
On September 15, biologists from Dalhousie University showed in a non‑peer‑reviewed preprint on bioRxiv how adult Drosophila thigh muscle recovers after severe damage. The muscle’s structure and mobility returned almost fully within a week.
Damage was induced by expressing light‑ or heat‑sensitive channels and then exposing flies to red light or heating to 37 °C for one‑two hours, causing continuous contraction without surgery. Immediately after stimulation the flies were nearly paralyzed, but movement speed returned to baseline after seven days, regardless of damage method.
Fluorescent Z‑disk markers showed that 50–60% of muscle area lost structure right away, but this proportion fell to zero by day three. Electron microscopy confirmed the Z‑disk spacing increased from 191 to 897 nm and returned to 187–191 nm after a week.
The key player was the protein filamin, which sits on the Z‑disk and crosslinks actin filaments of neighboring sarcomeres, switching between open and closed forms under load. Flies with normal filamin developed mild damage by week two and severe damage by week three, while those locked in the closed form showed protein aggregates already by week one and impaired recovery.
In 2024 the same lab showed filamin protects Z‑disks in wing muscle during contraction, but did not test whether muscle could rebuild myofibrils after severe destruction—this study answers that. Human filamin C mutations cause hereditary myofibrillar myopathies, linking the fly findings to
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On September 15, biologists from Dalhousie University showed in a non‑peer‑reviewed preprint on bioRxiv how adult Drosophila thigh muscle recovers after severe damage. The muscle’s structure and mobility returned almost fully within a week.
Damage was induced by expressing light‑ or heat‑sensitive channels and then exposing flies to red light or heating to 37 °C for one‑two hours, causing continuous contraction without surgery. Immediately after stimulation the flies were nearly paralyzed, but movement speed returned to baseline after seven days, regardless of damage method.
Fluorescent Z‑disk markers showed that 50–60% of muscle area lost structure right away, but this proportion fell to zero by day three. Electron microscopy confirmed the Z‑disk spacing increased from 191 to 897 nm and returned to 187–191 nm after a week.
The key player was the protein filamin, which sits on the Z‑disk and crosslinks actin filaments of neighboring sarcomeres, switching between open and closed forms under load. Flies with normal filamin developed mild damage by week two and severe damage by week three, while those locked in the closed form showed protein aggregates already by week one and impaired recovery.
In 2024 the same lab showed filamin protects Z‑disks in wing muscle during contraction, but did not test whether muscle could rebuild myofibrils after severe destruction—this study answers that. Human filamin C mutations cause hereditary myofibrillar myopathies, linking the fly findings to
🔗 Read original →
Frequent feeding cuts female killifish lifespan by a third, leaves males unchanged
Researchers at the Medical University of Vienna built a low‑cost automatic feeder for turquoise killifish (Nothobranchius furzeri) and tested feeding frequencies from two to 36 feedings per day while keeping the total daily food amount constant. The species naturally lives only four to six months, making it a rapid vertebrate model of aging.
Frequent feeding accelerated growth in both sexes, but female median lifespan fell from 21.9 to 15.1 weeks (≈30% reduction), whereas male median lifespan remained unchanged at 20–22 weeks. In a parallel experiment, vgll3‑edited males grew faster but lived 15% shorter.
The feeder uses an Arduino‑controlled stepper motor and interchangeable tubes to dispense food with milligram precision, costing about ≈€500 per 100 aquariums. It was deemed cheaper and more accurate than existing commercial options.
With fatty feeds such as Biomar and Otohime, females laid more eggs early but embryo survival dropped sharply, compressing the reproductive period
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Researchers at the Medical University of Vienna built a low‑cost automatic feeder for turquoise killifish (Nothobranchius furzeri) and tested feeding frequencies from two to 36 feedings per day while keeping the total daily food amount constant. The species naturally lives only four to six months, making it a rapid vertebrate model of aging.
Frequent feeding accelerated growth in both sexes, but female median lifespan fell from 21.9 to 15.1 weeks (≈30% reduction), whereas male median lifespan remained unchanged at 20–22 weeks. In a parallel experiment, vgll3‑edited males grew faster but lived 15% shorter.
The feeder uses an Arduino‑controlled stepper motor and interchangeable tubes to dispense food with milligram precision, costing about ≈€500 per 100 aquariums. It was deemed cheaper and more accurate than existing commercial options.
With fatty feeds such as Biomar and Otohime, females laid more eggs early but embryo survival dropped sharply, compressing the reproductive period
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Nature
An antagonistically pleiotropic gene regulates vertebrate growth, maturity, and lifespan
Nature Communications - Here they use killifish to reveal a stark genetic trade-off in aging. They found that disrupting the vgll3 gene accelerates early-life maturation and growth but directly...
HexemBio raises $15.5 million to rejuvenate blood stem cells, targets 2027 first‑in‑human trial
HexemBio has secured a total of $15.5 million for a therapy that temporarily returns aged hematopoietic stem cells to a lab‑made copy of the embryonic yolk‑sac niche where they originate. The round closed on 15 September with new investor Happiness Capital joining existing backers Draper Associates and Boost VC. The same synthetic yolk‑sac niche under
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HexemBio has secured a total of $15.5 million for a therapy that temporarily returns aged hematopoietic stem cells to a lab‑made copy of the embryonic yolk‑sac niche where they originate. The round closed on 15 September with new investor Happiness Capital joining existing backers Draper Associates and Boost VC. The same synthetic yolk‑sac niche under
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Nature
Modelling post-implantation human development to yolk sac blood emergence
Nature - A genetically inducible stem cell-derived embryoid model of early post-implantation human embryogenesis captures the codevelopment of embryonic tissue and extra-embryonic endoderm and...