Lifespan Research Institute researchers develop a CD38 peptide vaccine that elicits a strong immune response against age-associated CD38, improving physical performance, cognitive function, and metabolic health in aged mouse models, showcasing a novel immunotherapy approach for longevity.

Key points

• CD38 peptide vaccine elicits immune clearance of CD38-positive cells, restoring NAD+/NADH balance in aged tissues.
• Vaccinated mice show improved locomotor endurance, grip strength, and cognitive performance in water maze and object recognition tests.
• Liver proteomics reveals decreased p21 senescence marker and upregulated fatty acid metabolism and PPAR signaling after vaccination.

Why it matters: Demonstrates durable vaccination to modulate NAD+ metabolism and clear senescent cells, potentially transforming aging therapeutics.

Immortal Dragons, a Singapore-based longevity fund founded by Boyang Wang, strategically funds high-risk, high–impact projects. The fund prioritizes replacement-focused approaches—such as xenotransplantation, cryopreservation, and 3D bioprinting—over purely economic returns, aiming to catalyze breakthroughs in healthspan extension and inspire broader sector investment.

Key points

• Immortal Dragons deploys a $40M AUM fund via a flexible CVC model with a single LP, enabling rapid, independent investments free of rigid mandates.
• The fund targets replacement-driven interventions—xenotransplantation, cryopreservation, ex vivo 3D bioprinting of organs and tissues, and neural tissue augmentation—to pursue high-impact anti-aging strategies.
• By emphasizing underfunded, moonshot projects and role-model outliers over blockbuster pharma ventures, the fund seeks to demonstrate lifespan extension potential and catalyze broader capital inflows.

Why it matters: By focusing on replacement-based, high-risk longevity interventions, Immortal Dragons aims to break translational bottlenecks and redefine investment incentives in anti-aging research.

The team at Northwestern University develops engineered peptide amphiphile nanofibers that self-assemble through supramolecular polymerization to capture monomeric and oligomeric amyloid beta species. By incorporating bound Aβ42 into metastable nanostructures, the approach prevents neuronal uptake and maintains cell viability in vitro. This strategy targets early-stage soluble amyloid aggregates, offering a novel chemical tool to inhibit neurodegenerative processes associated with Alzheimer’s disease.

Key points

• Glycopeptide amphiphile nanofibers self-assemble via supramolecular copolymerization to form metastable structures that bind Aβ42 monomers and oligomers.
• Trehalose-functionalized peptides enhance nanofiber reactivity, physically entrapping soluble amyloid β42 and preventing neuronal uptake in iPSC-derived neuron cultures.
• Nanofiber treatment reduces Aβ-induced neuron death by over 60% in vitro, demonstrating cytoprotective efficacy against early Alzheimer’s pathogenesis.

Why it matters: Nanofiber trapping provides a chemical intervention to neutralize early soluble amyloid β, potentially transforming Alzheimer’s treatment at its source.

Researchers publishing in Neurotherapeutics conducted a Phase 1 trial evaluating the senolytic combination dasatinib and quercetin (D+Q) in five early-stage Alzheimer’s patients. Over a 12-week intermittent dosing regimen, investigators assessed amyloid and tau pathology alongside inflammatory and transcriptomic signatures. The study revealed no statistically significant changes in key Alzheimer’s biomarkers, highlighting translational challenges for senescence-targeting therapies.

Key points

• Intermittent dosing of dasatinib (100 mg) and quercetin (1 g) administered to five early-stage Alzheimer’s patients over 12 weeks.
• Multi-modal biomarker assessment included amyloid-β and tau quantification, inflammatory cytokine panels, lipidomic shifts, and PBMC transcriptomics.
• No statistically significant changes detected in Alzheimer’s biomarkers or SASP factors despite confirmed CNS penetration of dasatinib.

Why it matters: Null results underscore challenges in translating senolytics to treat neurodegeneration, urging development of more potent aging-targeted therapies.

Researchers at the Lifespan Research Institute introduce the pathogen control hypothesis, suggesting aging acts as an adaptive genetic program. They argue that by eliminating older hosts with chronic infections, populations reduce pathogen transmission, highlighting immune-driven mechanisms as key aging drivers.

Key points

• Pathogen control hypothesis frames aging as adaptive immune-driven senescence to curb chronic infections.
• Program-centered model contrasts with damage accumulation, emphasizing genetic regulation of lifespan.
• Eusocial insect data and security harness theory explain rare non-aging mutants and lifespan plasticity.

Why it matters: This evolutionary perspective shifts aging research toward immune system rejuvenation, offering a new paradigm for longevity therapeutics over damage-focused strategies.

An international team screened 66 natural metabolites and identified apigenin as a senomorphic flavonoid that suppresses the pro-inflammatory secretory phenotype of senescent cells by binding to PRDX6 and modulating HSPA8 activity. In cell and mouse models, apigenin reduced SASP factors, enhanced chemotherapeutic cytotoxicity, and improved physical and cognitive markers in prematurely aged mice.

Key points

• Apigenin binds PRDX6 to inhibit PLA2 activity, reducing arachidonic acid-mediated pro-inflammatory signaling.
• Disruption of HSPA8 interaction attenuates ATM–p38MAPK and PI3K/Akt/mTOR pathways, suppressing SASP factor secretion in senescent cells.
• In murine xenograft and irradiation-induced aging models, apigenin enhances chemotherapeutic apoptosis, reduces tumor burden, and reverses age-related functional decline.

Why it matters: By inhibiting PRDX6-driven SASP, apigenin offers a novel senotherapeutic strategy that enhances chemotherapy efficacy and mitigates age-related decline.

Researchers demonstrate that p62 protein depletion drives skin cell senescence through USP7 pathway dysregulation and show that replenishing p62 delays senescence markers in fibroblasts and keratinocytes, offering a novel target for anti-aging skin therapies.

Key points

• p62 directly binds USP7, preserving autophagic degradation and preventing p53/p21/p16-mediated senescence in dermal fibroblasts and keratinocytes.
• p62 knockout in keratinocytes accelerates skin thinning and increases inflammatory SASP markers (interleukins, TNF-α) in a mouse model.
• p62 overexpression halves UV-induced senescence rates in skin cells and reduces expression of USP7 and senescence biomarkers.

Why it matters: Targeting p62 replenishment offers a novel senomorphic strategy to maintain skin health and delay visible signs of aging.

A team led by Michael Levin at Tufts University’s Allen Discovery Center reveals that bioelectric voltage gradients across non-neuronal cells act as programmable “software” atop genetic “hardware.” By modulating ion channel and gap junction activity, they induce amphibian limb regeneration, cancer suppression, and novel organism constructs, offering new avenues for tissue engineering and longevity.

Key points

• Targeted ion channel drugs alter membrane voltage in planarian and frog models, inducing multi-headed regeneration without genetic changes.
• Maintaining electric connectivity in tumor-bearing amphibian cells suppresses oncogenic growth despite persistent oncoprotein expression.
• Programming bioelectric circuits in frog embryonic and human tracheal epithelial cells yields self-motile xenobots and anthrobots with self-replication and wound-healing capabilities.

Why it matters: Bioelectric pattern modulation represents a paradigm shift, offering a reversible, non-genetic approach to direct tissue regeneration, cancer suppression, and anti-aging therapies.

A team publishing in Aging Cell demonstrates that partial inhibition of pantothenate kinase reduces coenzyme A and iron-sulfur cluster levels, leading to HLH-30/TFEB activation and enhanced chaperone-mediated proteostasis in C. elegans and human cells. This mechanism improves stress resilience without lifespan extension, suggesting TFEB upregulation as a potential target for proteostasis disorders such as Alzheimer’s disease.

Key points

• Partial inhibition of pantothenate kinase in C. elegans reduces CoA and ISC levels to activate HLH-30/TFEB–driven chaperone expression.
• RNAi-mediated PanK reduction boosts proteostasis under heat and chemical stress in C. elegans and human cell models.
• CoA supplementation reverses benefits, confirming that decreased CoA–ISC levels drive TFEB activation for enhanced protein folding.

Why it matters: Targeting the PanK–CoA–ISC–TFEB axis offers a novel strategy to enhance proteostasis, potentially treating age-related neurodegenerative diseases.

Gero scientists present a quantitative thermodynamic model showing that human aging arises from both slow, irreversible entropy accumulation and dynamic stress-response instabilities. They classify interventions into Level-1 (molecular hallmarks), Level-2 (noise reduction), and Level-3 (entropic damage reversal) therapies to target age-related decline.

Key points

• Dual aging mechanism: irreversible entropic damage and reversible stress fluctuations
• Level-1 therapies target molecular hallmarks: CR mimetics, senolytics, telomere activators
• Level-2 interventions aim to reduce physiological noise and extend healthspan by 30–40 years
• Level-3 strategies focus on halting or reversing accumulated entropic damage to push lifespan beyond 150 years
• Caloric restriction and rapamycin remain top benchmarks for lifespan extension in animal models
• Quantitative model predicts resilience divergence near maximal human lifespan (120–150 years)

Why it matters: This framework shifts longevity research from isolated hallmarks to a system-level, entropy-driven view, highlighting why incremental therapies cannot fully arrest aging. It provides clear directives for next-generation interventions capable of extending both healthspan and maximum lifespan beyond existing limits.

A pilot study by OneSkin and academic collaborators evaluates the senomorphic peptide OS-01 in women aged 60–90. Over 12 weeks, researchers applied the peptide topically and monitored skin barrier function, transepidermal water loss, and systemic cytokine profiles via mass spectrometry. They observed localized peptide retention, reduced IL-8 levels, and notable improvements in hydration, elasticity, and appearance.

Key points

• OS-01, a senomorphic peptide, was topically applied to skin areas in 60 women aged 60–90.
• Mass spectrometry confirmed OS-01 remains localized, with no detectable systemic presence.
• Treated cohort exhibited significant reductions in pro-inflammatory cytokines IL-8 and balanced IL-10.
• Instrumental assays showed improved barrier function, increased moisture, and reduced transepidermal water loss.
• Participants reported enhanced skin elasticity, hydration, and visual appearance post-treatment.

Why it matters: Targeting skin senescence with a localized peptide that also lowers systemic inflammation suggests a novel therapeutic avenue for aging-related disorders. By modifying harmful cell signals rather than destroying cells, OS-01 may offer safer, more targeted interventions over existing senolytics, paving the way for broader applications in healthy aging.

An aging research team applies miRNA enrichment analysis and an age-related genetic database to isolate a four-strand microRNA cocktail (E5) within stem-cell–derived extracellular vesicles. Delivered to senescent fibroblasts, E5 downregulates p16, p21 and inflammatory interleukins, outperforming native vesicles. In naturally aged mice, systemic E5 injections reduce senescence and DNA damage markers in liver tissue, highlighting a non-senolytic approach to cellular rejuvenation.

Key points

• Four-miRNA cocktail (E5) derived from stem cell EVs modulates senescence.
• Delivery via extracellular vesicles reduces SA-β-gal activity by ~30% in fibroblasts.
• E5 downregulates p21, p16, IL-1β and IL-6 through PCAF and HIPK2 suppression.
• In 24-month-old mice, systemic E5 dosing lowers senescence and DNA damage markers in liver tissue.
• Non-senomorphic approach spares cell viability while targeting aging pathways.

Why it matters: This miRNA-loaded EV approach offers a non-senolytic alternative that reprograms aging cells without inducing cell death, potentially reducing side effects of current therapies. By targeting multiple senescence pathways, it could pave the way for precise, rejuvenative treatments in age-related diseases.

Researchers at UT Health San Antonio define immune resilience as the capacity to balance inflammation and immune defense, stratifying over 17,000 participants into preservers, reconstituters, or degraders based on T-cell markers and TCF7 expression. Their analysis reveals a significant survival advantage linked to robust immune profiles.

Key points

• Classified ~17,500 individuals into IR-preservers, reconstituters, and degraders using CD4/CD8 ratios
• Identified SAS-1 and MAS-1 molecular signatures via transcriptomic and proteomic profiling
• Demonstrated TCF7 transcription factor’s central role in maintaining T-cell multipotency and survival
• Found up to 15-year survival advantage for high-resilience individuals aged 40–70
• Highlighted midlife (40–70 years) as a critical intervention window for preserving immune resilience

Why it matters: This research reframes aging trajectories by positioning immune resilience as a modifiable determinant of longevity. By identifying TCF7 and molecular signatures linked to survival, it opens avenues for targeted interventions to preserve immune function and mitigate age-associated mortality risk.

Vascular calcification arises when phosphate triggers calcium crystals in arteries, stiffening them. In cell and mouse models, fisetin raised DUSP1 levels to block the p38/MAPK pathway, reversing calcification markers. This suggests a new senolytic approach to safeguard vascular health in chronic kidney disease contexts.

Key points

• Fisetin increases DUSP1 to inhibit p38/MAPK, reducing vascular calcification markers in cells.
• Mouse studies confirm fisetin’s ability to prevent arterial calcium deposition in vivo.
• Targeting senescence pathways offers a novel intervention for blood vessel stiffening, especially in CKD models.

A recent 48-week randomized trial by Lifespan.io explored rapamycin's impact on aging. The study found that women experienced significant lean mass improvements and reduced pain compared to men. These results suggest that controlled low-dose rapamycin could influence healthspan, warranting further investigation in longevity research.

A recent study reported by Lifespan.io revealed that engineered exosomes laden with OSK plasmids can reprogram aging spinal disc cells in rats. This innovative method, akin to resetting cellular clocks, restored disc integrity and alleviated pain. The findings offer a promising strategy for regenerative therapies targeting chronic back conditions.

Researchers at UCSF, under Dr. Dena Dubal and reported by Anna Drangowska-Way in April 2025, discovered that reactivation of the silent X chromosome in aged female mice’s hippocampi is linked to enhanced cognition. Using cross-strain experiments, they observed increased PLP1 expression, suggesting innovative intervention strategies for age-related cognitive decline.

A 2025 study revealed that targeting ADAM19, a protein linked to cellular aging, significantly cuts down senescence markers and inflammation. Researchers from the Buck Institute and Lifespan Research Institute used flies, mice, and human cells to demonstrate reduced gut permeability when ADAM19 activity was blocked. This finding opens the door for innovative strategies in longevity research.

The article by Josh Conway (Mar 31, 2025) offers a detailed insight into how aging alters adrenal gland function, notably affecting DHEA and cortisol production. In a well-documented context, it illustrates how such imbalances can influence overall wellbeing, providing an example of the health challenges faced with advancing age.

In a 2025 Aging Cell study, researchers under Dr. Vadim Gladyshev demonstrated that elamipretide, administered via osmotic pumps in Black 6 mice, reduced frailty and enhanced cardiac performance. This intervention underscores the potential of mitochondrial therapies for age-related conditions.