Powerful Anti Aging Molecule Group Buy: DANA (17%+ Lifespan Extension)

#1

The study identifies a completely novel driver of systemic aging and introduces a small molecule that shows incredible synergy with rapamycin.
The molecule used in the paper is
2,3-dehydro-2-deoxy-N-acetylneuraminic acid

C9-BA-DANA (C9-butyl-amide-DANA) would probably be the best option as of now to use as it is the most extensively studied selective NEU1 inhibitor. It is over 200 times more selective for NEU1 than the other NEUs, demonstrating an IC50 of 10 µM for NEU1 but failing to inhibit the others even at 1000 µM. It has already been successfully tested in live mice to block NEU1-mediated inflammation

C9-BA-DANA paper:
Neuraminidase-1 (NEU1): Biological Roles and Therapeutic Relevance in Human Disease

Link to the anti aging paper:

Elastin-derived extracellular matrix fragments drive aging through innate immune activation

Here is a recent YouTube video about it:
This Tiny Molecule Blocks Aging

DANA + Rapamycin Show Massive Synergistic Anti-Aging Effects (17%+ Lifespan Extension)

A landmark study just published in Nature Aging identifies a completely novel driver of systemic aging — degraded elastin fragments circulating in our blood — and introduces a small molecule called DANA that blocks this pathway by inhibiting a transmembrane signaling protein called NEU1 (neuraminidase 1). On its own, DANA extended lifespan by up to 17% in naturally aged mice. Combined with rapamycin, the results were even more striking.

What’s Actually Driving the Aging?

As we age, our extracellular matrix (the structural scaffolding between cells) breaks down and releases protein fragments called matrikines into the bloodstream. The researchers measured four major types — elastin, hyaluronic acid, fibronectin, and collagen fragments — and found that all increase with age in both mice and humans. But elastin-derived fragments were by far the most damaging.

Within elastin fragments, a specific six-amino-acid sequence called the E-motif (VGVAPG) is the culprit. This motif activates monocytes and macrophages through the elastin receptor complex, where NEU1 acts as the signal transducer. The result is a cascade of chronic innate immune activation → inflammatory cytokine release (IL-1β, IL-6, MCP-1, TNF) → abnormal T and B cell expansion → full-blown systemic inflammaging. When they knocked out NEU1 specifically in myeloid cells, the entire aging cascade was abolished.

DANA Monotherapy in Naturally Aged Mice

DANA was given to wild-type, naturally aged mice (starting at ~60 weeks) via weekly intraperitoneal injection at 2.5 mg/kg. Results:

  • Lifespan extension: +17.4% median lifespan in males, +12.2% in females
  • Body composition: Significant reductions in body weight, fat mass, and abdominal fat with preserved lean tissue
  • Mobility: Improved treadmill endurance, open-field locomotor activity, and grip strength
  • Reduced kyphosis: Less spinal curvature (a classic aging phenotype)
  • Liver health: Reduced hepatic steatosis, lower AST/ALT, and lower liver triglyceride content
  • Metabolic markers: Improved glucose, LDL, and triglyceride levels
  • Inflammaging: Broad suppression of 22 inflammatory markers measured in serum

DANA + Rapamycin Synergy

This is where it gets really exciting. They co-administered DANA (2.5 mg/kg) + rapamycin (6 mg/kg), both once weekly. The combination significantly outperformed either monotherapy across the board:

  • Lifespan: The combo group lived significantly longer than DANA-only (p=0.02) and rapamycin-only (p=0.04) groups
  • Body weight & composition: Greatest reduction in body weight and best fat-to-lean tissue ratio of any group
  • Inflammation: Lowest IL-1β and MCP-1 levels — significantly better than either drug alone
  • Tissue-level improvements: Largest muscle fiber increases, greatest WAT adipocyte shrinkage, and most liver triglyceride reduction

Notably, DANA and rapamycin work through completely different mechanisms — DANA blocks the matrikine/NEU1/innate immune axis while rapamycin targets mTOR — which likely explains why they synergize so well.

Validated in Pigs and Humanized Mice

They didn’t stop at mice. In Yorkshire pigs given E-motif injections twice weekly for 16 weeks, co-administration of DANA normalized markers of liver function (AST, ALP, albumin), kidney function (BUN, creatinine), and metabolic health (glucose, LDL, triglycerides). In immune-humanized mice injected with actual human elastin fragments, DANA produced nearly identical protective effects across the same biomarkers.

Human Cohort Data

Analysis of 1,068 human serum samples confirmed that circulating elastin fragment levels strongly correlate with age (p<0.0001) and are positively associated with BMI, hypertension, liver dysfunction, dyslipidemia, kidney impairment, hyperglycemia, chronic inflammation, and even mild thyroid dysfunction. Individuals in the “high elastin fragment” group had significantly worse outcomes across virtually every aging-related biomarker measured.

Safety & Dosing Considerations

  • Dose used: 2.5 mg/kg once weekly (IP injection in mice and pigs)
  • No reported adverse effects across any of the animal models
  • DANA shares a parent molecular scaffold with FDA-approved neuraminidase inhibitors like zanamivir (Relenza) and oseltamivir (Tamiflu), which have well-established human safety profiles
  • DANA works downstream of the elastin fragments themselves — it doesn’t immediately reduce circulating fragment levels, but long-term treatment gradually lowers them as the aging process slows
5 Likes
#2

What is the correct name of the compound {DANA]?

As a basic search DANA shows nothing as compound.

#3

See related discussion here: Elastin Fragments Identified as Drivers of Systemic Aging

1 Like
#4
  • DANA (2,3-dehydro-2-deoxy-N-acetylneuraminic acid) – weak NEU1 inhibitor, proof-of-concept. Can combine with rapamycin for synergy.

See full discussion here: Elastin Fragments Identified as Drivers of Systemic Aging

1 Like
#5

FWIW…

Quick search

Key purchasing details for this compound (CAS 24967-27-9 ) include:

  • Purity Levels : Available in purities ranging from ≥93% (TLC) to ≥95% (HPLC/TLC).
  • Physical Properties : It appears as a white to pale yellow powder with a melting point of 227–228 °C (for the sodium salt) or 134 °C (free acid), and is soluble in water.
  • Storage Requirements : Products must be stored at −20°C in a desiccated environment due to hygroscopic nature.
  • Applications : Widely used as a tool compound to inhibit bacterial, viral, and mammalian neuraminidases (sialidases) in research regarding viral infections , vaccine development , and cell signaling .
  • Pricing : Costs vary by supplier and quantity, with examples ranging from $37 for 1 mg (Cayman Chemical) to $149.24 for 5 mg (Sigma-Aldrich).
#7

The above info is not useful to the thread

#8

@MolecularResearch Curious why you say that? He identified couple sources and their price. do you have cheaper sources?

1 Like
#9

Any studies in humans?

#10

A summary and analysis of the video posted earlier on this topic:

I. Executive Summary

This report evaluates a popularized interpretation of recent research concerning extracellular matrix (ECM) degradation, specifically focusing on elastin-derived matrikines and their role in mammalian aging. The core thesis posits that aging is not a passive decay process but an active, cyclical inflammatory cascade initiated by ECM fragmentation. The source transcript correctly identifies that breakdown products—notably elastin fragments containing the VGVAPG hexapeptide (E-motif)—act as damage-associated molecular patterns (DAMPs). These matrikines bind to the elastin receptor complex, activating Neuraminidase-1 (Neu1), which subsequently drives downstream cellular senescence, characterized by the upregulation of p16, p21, and p53, alongside canonical inflammatory markers.

The translational promise highlighted in the transcript centers on DANA (2-deoxy-2,3-dehydro-N-acetylneuraminic acid), a small-molecule sialidase inhibitor. The presented preclinical data (murine and porcine models) demonstrates that Neu1 inhibition via DANA ameliorates metabolic dysfunction, preserves lean tissue, and extends murine lifespan by approximately 10-17%. While biologically plausible and evolutionarily conserved, the speaker aggressively extrapolates these preclinical findings to human longevity applications, minimizing critical translational gaps.

Systemic Neu1 inhibition in humans carries immense unaddressed safety risks. Congenital Neu1 deficiency causes sialidosis (mucolipidosis type I), a severe lysosomal storage disorder leading to neurodegeneration and early mortality. The therapeutic window for a neurominidase inhibitor to safely blunt matrikine signaling without inducing lysosomal pathology remains entirely undefined in clinical populations. Furthermore, the speaker transitions abruptly from discussing experimental Neu1 inhibition to promoting commercially available, unvalidated biomarker algorithms and extreme “dolphin-like” omega-3 indices. These lifestyle interventions, while directionally aligned with general anti-inflammatory principles, are mechanically divorced from the specific Neu1/matrikine pathway detailed in the primary thesis. Actionable clinical intelligence from this transcript is limited to standard inflammatory surveillance; the targeted pharmacological manipulation of the ECM-aging axis remains strictly experimental.

II. Insight Bullets

  1. Active ECM Dynamics: The extracellular matrix is a bioactive signaling reservoir, not an inert structural scaffold.
  2. Matrikine Generation: Enzymatic degradation of the ECM yields matrikines—bioactive protein fragments that drive systemic signaling.
  3. Elastin as DAMP: Elastin fragments (ELN) function as damage-associated molecular patterns, triggering innate immune responses.
  4. Correlative Human Data: Elevated circulating elastin fragments correlate with metabolic syndrome and advanced chronological age in humans (n=1,068).
  5. Murine Causality: Intravenous administration of ELN fragments in mice induces accelerated biological aging phenotypes.
  6. Senescence Induction: ELN fragments directly upregulate canonical senescence markers (p16, p21, p53).
  7. The E-Motif Trigger: The specific biological trigger is a six-amino-acid sequence within elastin: VGVAPG (valine-glycine-valine-alanine-proline-glycine).
  8. Target Pathway: The E-motif initiates cellular cascades via activation of the enzyme Neuraminidase 1 (Neu1).
  9. Pharmacological Intervention: DANA is utilized as a small-molecule inhibitor of Neu1 to block this specific signal transduction.
  10. Preclinical Efficacy: Neu1 inhibition via DANA improves body composition, hepatic lipid accumulation, and skin integrity in murine models.
  11. Murine Lifespan Extension: DANA administration extended lifespan by 17.4% in male mice and 12.2% in female mice.
  12. Porcine Conservation: Yorkshire pig models confirm metabolic conservation of the ELN/Neu1 pathway in higher-order mammals.
  13. Cyclical Pathology: Aging operates as a positive feedback loop: inflammation drives ECM breakdown, producing matrikines that drive further inflammation.
  14. Upstream Effects of Downstream Blocks: Long-term Neu1 inhibition eventually lowers circulating ELN fragments by breaking the inflammatory feedback loop.
  15. Translational Divergence: No current human therapeutic specifically targets the E-motif/Neu1 axis; actionable advice pivots entirely to general anti-inflammatory lifestyle protocols.

III. Adversarial Claims & Evidence Table

Claim from Video Speaker’s Evidence Scientific Reality (Current Data) Evidence Grade Verdict
Elastin fragments in blood strongly associate with older age and poor metabolic health. Observational study of 1,068 individuals. Validated. Elastin-derived peptides correlate with cardiovascular and metabolic pathology. Source unverified in live search, proxy validation via literature. Level C Strong Support
The E-motif (VGVAPG) drives systemic aging and early death. Tail injections in mice causing physical decline and senescence. VGVAPG is a known pathogenic driver in vascular and pulmonary tissue in vitro and in vivo. Source unverified in live search. Level D Plausible
DANA safely extends lifespan and healthspan by blocking Neu1. Animal models (mice, pigs) showing 12-17% lifespan increase. DANA is a pan-sialidase inhibitor. Long-term human safety is completely unproven. Neu1 loss-of-function in humans causes Sialidosis. Source unverified in live search. Level D Translational Gap / Safety Warning
An extreme “dolphin-like” Omega-3 index dramatically lowers biological age to ~15.4 years. Personal anecdote, PhenoAge test, “100 Health” app. High O3 index reduces triglycerides and cardiovascular risk. Extreme supraphysiological levels risk atrial fibrillation and hemorrhage. PhenoAge algorithms are easily skewed by isolated biomarkers. Source unverified in live search. Level E Unsupported / Safety Warning
“A protocol” can triple LDLR mRNA to drop ApoB without statins. Teased proprietary app insight. Unverified claim. While PCSK9 inhibitors and berberine affect LDLR recycling/transcription, the specific undisclosed intervention cannot be evaluated for safety or efficacy. Level E Unsupported

IV. Actionable Protocol (Prioritized)

High Confidence Tier (Level A/B Evidence)

  • ApoB & Lipid Surveillance: Continuous monitoring of Apolipoprotein B as the primary driver of atherogenic ECM damage.
  • Standard Inflammatory Profiling: Regular monitoring of high-sensitivity C-Reactive Protein (hsCRP). Maintain levels strictly below 1.0 mg/L to minimize systemic matrix metalloproteinase (MMP) activation.
  • Omega-3 Optimization: Maintain an Omega-3 Index of 8% to 12%. Do not pursue the speaker’s “dolphin-like” extremes, as RCTs indicate an inflection point where supraphysiological EPA/DHA intake increases the risk of atrial fibrillation and lipid peroxidation.

Experimental Tier (Level C/D Evidence with High Safety Margins)

  • Advanced Cytokine Tracking: Monitoring TNF-α and IL-1β can provide deeper visibility into the senescent-associated secretory phenotype (SASP), which drives the degradation of elastin.
  • Myeloperoxidase (MPO) & MDA: Tracking oxidative stress markers to proxy the oxidative degradation of structural tissues.

Red Flag Zone (Safety Data Absent)

  • Neu1 / Sialidase Inhibitors: Attempting to source or synthesize DANA (or similar small molecules like zanamivir/oseltamivir off-label) for systemic longevity purposes. Neu1 is required for normal lysosomal clearance; inhibition poses severe risks of neurodegeneration and intracellular toxic accumulation.
  • Unverified LDLR Transcript Manipulation: Engaging in opaque supplement protocols aimed at tripling LDLR mRNA without clinical oversight. Hepatotoxicity and unintended lipid compartmentalization are primary risks.

V. Technical Mechanism Breakdown

The transcript outlines the transition from structural biology to signal transduction via the Elastin Receptor Complex (ERC).

  1. ECM Cleavage & Matrikine Formation: Endogenous matrix metalloproteinases (MMPs), elastases, and cathepsins upregulate in response to baseline oxidative stress or minor injury. These enzymes cleave highly cross-linked elastin polymers, releasing soluble elastin-derived peptides (EDPs), specifically exposing the hydrophobic hexapeptide VGVAPG (the E-motif).
  2. ERC Activation: The VGVAPG motif acts as an agonistic ligand for the Elastin Binding Protein (EBP), a spliced variant of beta-galactosidase. EBP is non-covalently associated on the cell surface with protective protein/cathepsin A (PPCA) and the membrane-bound sialidase Neuraminidase 1 (Neu1).
  3. Sialidase Activity & Propagation: Ligand binding to EBP triggers a conformational change that fully activates Neu1. Neu1 subsequently strips sialic acid residues from adjacent cell-surface glycoproteins, notably Toll-like Receptor 4 (TLR4) and the Insulin-like Growth Factor 1 Receptor (IGF-1R).
  4. Downstream Pro-Aging Kinase Cascades: The desialylation of TLR4 removes steric hindrance, leading to receptor dimerization, recruitment of MyD88, and downstream activation of NF-κB. This upregulates the transcription of pro-inflammatory cytokines (IL-1β, TNF-α) and further MMPs. Simultaneously, the pathway drives cellular senescence programs via the stabilization of cyclin-dependent kinase inhibitors p16^(INK4a) and p21^(Cip1), and the tumor suppressor p53.
  5. The Pharmacological Blockade (DANA): 2-deoxy-2,3-dehydro-N-acetylneuraminic acid is a transition-state analog that competitively inhibits Neu1. By occupying the active site of Neu1, DANA prevents the desialylation of TLR4 and other receptors, thereby aborting the signal transduction from the VGVAPG matrikine before it can initiate NF-κB transcription or stabilize p53, severing the feed-forward loop of age-related ECM degradation.