A coalition of aging researchers, clinicians, and DIY biohackers are evaluating low-dose rapamycin’s capacity to induce autophagy and extend healthspan. While animal models report significant lifespan gains, human evidence remains limited. The debate centers on regulatory constraints, ethical implications of off-label prescribing, and the economic barriers to clinical trials for generic drugs.

Key points

• Rapamycin inhibits mTORC1 to enhance autophagy and slow cellular aging in preclinical models.
• Widespread off-label prescriptions reflect growing interest but lack rigorous human trial data.
• Regulatory and economic barriers hinder formal approval of rapamycin for aging indications.

Why it matters: Validating rapamycin’s anti-aging effects could revolutionize therapeutic approaches to age-related disease and drive regulatory reform around aging as a treatable condition.

Researchers in a collaborative study evaluate DT-109, an orally deliverable tripeptide, for its effects on advanced atherosclerosis and vascular calcification in cynomolgus monkeys. Administered daily alongside a high-cholesterol diet, DT-109 significantly reduces lesion formation, inflammatory signaling, and arterial calcification while promoting smooth muscle cell contractile marker expression. These findings suggest a multifaceted therapeutic approach to combat cardiovascular disease by targeting inflammasome pathways and plaque stability.

Key points

• Orally administered DT-109 (Gly-Gly-Leu) peptide at 150 mg/kg/day in cynomolgus monkeys.
• Five-month treatment with a cholesterol-rich diet showed significant reductions in aortic and coronary lesion size.
• DT-109 downregulates pro-inflammatory genes NLRP3, AIM2, CASP1 and oxidative stress markers NCF2, NCF4.
• Treatment reduces vascular calcification and macrophage content while increasing SMC contractile markers ACTA2, CNN1, TAGLN.
• In vitro assays confirm DT-109 inhibits NLRP3 inflammasome activation and smooth muscle cell calcification.

Why it matters: These results demonstrate a novel peptide-based strategy that combines anti-inflammatory and anti-calcific actions to address advanced atherosclerosis, a leading cause of cardiovascular mortality. By demonstrating efficacy in primate models, DT-109 bridges the gap between rodent research and human application, offering a promising route to more effective, orally available therapies that can regress plaque and restore vascular function.

Researchers publishing in Aging Cell report that senescent macrophages in old skeletal muscle release the antiangiogenic VEGF-A165B isoform, impairing endothelial function and slowing revascularization in peripheral arterial disease models.

Key points

• Senescent macrophages accumulate in ischemic skeletal muscle of aged mice.
• Transplantation experiments show these macrophages inhibit revascularization.
• Senescent cells upregulate antiangiogenic VEGF-A165B isoform secretion.
• Elevated plasma VEGF-A165B correlates with disease severity in elderly PAD patients.
• Senolytics like dasatinib plus quercetin offer a strategy to clear senescent macrophages.

Why it matters: Uncovering senescent macrophages as drivers of poor vascular regeneration identifies a novel therapeutic target. This insight paves the way for senolytic interventions to improve blood flow recovery in age-related vascular diseases, potentially enhancing healthspan.

Researchers employ o-vanillin and RG-7112 in sparc–/– mice, targeting accumulated senescent cells in intervertebral discs. Oral administration clears these cells, lowers SASP-driven inflammation, improves vertebral bone quality, and reduces pain marker expression in the spinal cord through p53/MDM2 inhibition and senomorphic activity.

Key points

• Oral o-vanillin and RG-7112 synergistically clear senescent cells in sparc–/– mouse discs.
• Senolytic treatment markedly reduces SASP factor release and local inflammation in IVD tissue.
• Cleared senescence correlates with lower disc degeneration scores and restored ECM integrity.
• Vertebral bone quality improves, and expression of spinal cord pain markers decreases post-treatment.
• RG-7112 blocks p53/MDM2 interaction to induce senescent cell apoptosis; o-vanillin acts as a senomorphic agent.

Why it matters: By demonstrating that targeted senolytic therapy can reverse established disc degeneration and alleviate chronic back pain, this study shifts the paradigm from symptomatic management to disease modification. It highlights a translational pathway for combining natural senomorphics with targeted apoptosis inducers to tackle age-related disorders driven by cellular senescence.

Researchers used the 5xFAD Alzheimer’s mouse model to study microglial β2 adrenergic receptor (β2AR) signaling. They found that activating β2AR with norepinephrine agonists lowered neuroinflammation, amyloid plaque accumulation, and neuritic damage, while receptor blockade worsened pathology, identifying β2AR as a potential early therapeutic target.

Key points

• Microglial β2AR expression decreases early in 5xFAD cortex, especially near plaques.
• Blockade of β2AR worsens amyloid load, inflammation, and neuritic damage.
• β2AR stimulation via agonists reduces plaque burden and attenuates neuroinflammation.
• Early loss of cortical norepinephrine projections precedes microglial β2AR downregulation.
• Study validates β2AR-mediated noradrenergic modulation of microglia as therapeutic target.

Why it matters: By highlighting microglial β2AR as a modifiable switch in Alzheimer’s neuroinflammation, this work shifts focus from direct amyloid clearance to immune regulation. Early targeting of this pathway could enhance disease-modifying therapies and outperform existing approaches by intervening before extensive neuronal damage occurs.

Ohio State University scientists deliver PDGF-BB protein to spinal cord injuries, altering pericyte behavior from inhibitory to supportive. This promotes angiogenesis that forms conduits guiding axon regeneration in mice, leading to improved motor function and reduced pain.

Key points

• Single PDGF-BB injection applied seven days post–spinal cord injury in mice.
• PDGF-BB reprograms pericytes to switch from inhibitory to pro-angiogenic phenotype.
• Induced angiogenesis creates vascular scaffolds guiding axonal regeneration.
• Treated mice exhibit restored hind limb motor control and sensory conduction.
• Electrophysiological tests confirm functional neural reconnection and reduced pain.

Why it matters: This approach shifts the paradigm in spinal cord repair by harnessing endogenous pericyte plasticity for vascular-guided axon regeneration. It offers a targeted, protein-based therapy that outperforms cell clearance strategies, paving the way for translational advances in central nervous system trauma.

Researchers on Fight Aging! describe how a six-month methionine-restricted diet in 18-month-old mice improved multiple health markers—metabolism, neuromuscular and lung performance—and reduced frailty. Despite no change to epigenetic clock readings, snRNA-seq and ATAC-seq revealed cell-specific responses, suggesting targeted antiaging pathways.

Key points

• Late-life methionine restriction enhances metabolic, neuromuscular and lung function in aged mice.
• Dietary MetR does not alter DNA methylation-based epigenetic age in mice or human cells.
• snRNA-seq and ATAC-seq reveal cell-type-specific molecular adaptations to MetR.

Think of epigenetic clocks as molecular speedometers. In a sample of 948 US adults (mean age 62), researchers correlated self-reported physical activity with eight DNA methylation-based clocks, including GrimAge and HorvathAge. Higher exercise levels aligned with younger SkinBloodAge and LinAge readings, particularly among non-Hispanic whites with BMI 25–30 and former smokers. This suggests fitness routines could serve as practical interventions and quick biomarkers for monitoring aging trajectories.

Key points

• Physical activity associates with younger biological age across eight epigenetic clocks.
• SkinBloodAge and LinAge showed the strongest exercise-related effects, especially in specific subgroups.
• Combining fitness measures with epigenetic profiling offers a scalable approach for monitoring anti-aging interventions.