Computational infrastructure for longevity biology
KPP processes biological data through a three-stage pipeline. Each stage produces verifiable outputs that feed directly into the next, with a TTTPS timestamp anchoring every result to a specific point in time.
Internal execution order when calling POST /api/v1/longevity/protocol. Stages chain conditionally on bloodwork results.
| Item | Detail |
|---|---|
| Biological context | PhenoAge (Levine 2018) is a composite biomarker derived from clinical blood panels. It reliably outperforms chronological age as a predictor of all-cause mortality and disease risk. Telomere length percentile provides an orthogonal structural view of cellular aging. Together they define the intervention target before any therapeutic design begins. |
| Input parameters |
wbcWhite blood cell count (10³/µL)
rbcRed blood cell count (10⁶/µL)
hemoglobinHemoglobin (g/dL)
plateletsPlatelet count (10³/µL)
glucoseFasting glucose (mg/dL)
creatinineSerum creatinine (mg/dL)
albuminSerum albumin (g/dL)
altAlanine aminotransferase (U/L)
total_cholesterolTotal cholesterol (mg/dL)
lymphocyte_pctLymphocyte percentage (%)
ageChronological age (years), used for delta computation
|
| Output |
biological_age (years), telomere_percentile (0–100), phenoage_delta (chronological minus biological), recommended protocol stage (0–3), TTTPS timestamp
|
| Downstream use | The protocol recommendation maps directly to Stage 1 circuit targets. A delta < −5 years typically warrants senolytic intervention; the recommendation field encodes this as a structured enum for programmatic routing. |
| Item | Detail |
|---|---|
| Biological context | Senescent cells accumulate with age and secrete a pro-inflammatory SASP (Senescence-Associated Secretory Phenotype). SynNotch is a synthetic receptor system that activates gene expression only when two surface markers are co-detected, reducing off-target cytotoxicity. The AND-gate architecture ensures the payload fires only in cells that present both the primary receptor and a co-ligand, a selectivity constraint not achievable with single-input receptors. |
| Input parameters |
target_receptorPrimary surface marker on target senescent cells (e.g.
p16INK4a, B2M)payload_geneEffector gene to express upon AND-gate activation (e.g.
CASP9, IL-2)co_ligandOptional secondary marker for AND-gate specificity
cell_contextCell type background for promoter selection (
T-cell, NK, fibroblast) |
| Output | Full circuit specification: receptor binding domain, transmembrane linker, transcriptional activator, promoter cassette, payload expression construct, returned as structured JSON with optional SBOL-compatible annotation, plus TTTPS timestamp |
| Downstream use |
The circuit output passes directly into Stage 2. The payload_gene from Stage 1 becomes the target_mRNA for riboswitch design, adding a ligand-gated expression layer on top of the AND-gate logic.
|
| Item | Detail |
|---|---|
| Biological context | Riboswitches are structured RNA elements in the 5' UTR that undergo conformational change upon small-molecule binding, controlling translation of the downstream ORF. Embedding a riboswitch upstream of the Stage 1 payload gene creates a third control layer: the circuit only activates (AND-gate), in the right cell (co-ligand), and when the exogenous ligand is present. This enables dose-titratable and temporally reversible control over therapeutic expression. |
| Input parameters |
target_mrnamRNA to be regulated, typically the payload gene from Stage 1
trigger_ligandSmall molecule that triggers conformational switch (e.g.
theophylline, tetracycline)switch_type
ON (ligand activates translation) or OFF (ligand suppresses translation)n_candidatesNumber of candidate sequences to return (default 3)
|
| Output | For each candidate: nucleotide sequence, secondary structure dot-bracket notation, minimum free energy (MFE, kcal/mol), predicted switching efficiency (%), confidence score, TTTPS timestamp. Sequences ranked by MFE delta between apo and holo states. |
| Downstream use | Candidate sequences are ready for synthesis and in-vitro validation. The MFE and confidence scores provide a ranked shortlist for experimental prioritization. All three outputs are included in the full-pipeline consolidated report. |
| Item | Detail |
|---|---|
| Biological context | The longevity protocol endpoint chains Stage 0 → 1 → 2 in a single call. Intermediate results are passed automatically; the caller supplies all inputs upfront and receives a consolidated output plus a three-link TTTPS audit chain that anchors the entire computation to immutable timestamps. |
| Input parameters |
Union of Stage 0, 1, and 2 inputs. Blood markers are required. Circuit parameters (target_receptor, payload_gene, trigger_ligand) are required for the downstream stages. Absent parameters cause the pipeline to halt at the last completable stage and return partial results.
|
| Output |
phenoage_result (Stage 0 output), circuit_design (Stage 1 output), riboswitch_candidates (Stage 2 output), tttps_chain (array of 3 timestamps, one per stage), pipeline_version
|
| Downstream use |
The tttps_chain provides the audit record required for regulatory submissions. Each timestamp is independently verifiable against the KPP root certificate. FDA 21 CFR Part 11 and EU MDR audit trail requirements are satisfied by the chain alone, without additional logging infrastructure on the caller's side.
|
Every API call returns a TTTPS (TLS Time Token Protocol Specification) timestamp, a cryptographically signed record binding the computation output to a precise point in time.
For the full pipeline endpoint, the response contains a tttps_chain array with three entries, one per stage. Regulators can verify the chain to confirm that Stage 2 riboswitch candidates were derived from the specific Stage 0 blood values in the same computation, with no opportunity to substitute intermediate results. This satisfies FDA 21 CFR Part 11 electronic records requirements and EU MDR Annex II documentation obligations without additional infrastructure on the caller side.
# Install pip install httpx import httpx client = httpx.Client( base_url="https://kpp.kenosian.com", headers={"X-API-Key": "your-key"} ) # Stage 0: Biological age stage0 = client.post("/api/v1/analyze/bloodwork", json={ "age": 52, "wbc": 5.8, "rbc": 4.6, "hemoglobin": 14.2, "platelets": 220, "glucose": 94, "creatinine": 0.9, "albumin": 4.1, "alt": 22, "total_cholesterol": 188, "lymphocyte_pct": 28.4 }) bio_age = stage0.json()["biological_age"] # e.g. 44.7 delta = stage0.json()["phenoage_delta"] # +7.3 years younger ts0 = stage0.json()["tttps_timestamp"] # TTTPS anchor # Stage 1: Senolytic circuit design stage1 = client.post("/api/v1/design/synnotch", json={ "target_receptor": "p16INK4a", "payload_gene": "CASP9", "co_ligand": "B2M", "cell_context": "NK" }) # Stage 2: Riboswitch for conditional payload control stage2 = client.post("/api/v1/design/riboswitch", json={ "target_mrna": "CASP9", "trigger_ligand": "theophylline", "switch_type": "ON", "n_candidates": 3 }) candidates = stage2.json()["candidates"] # [{"sequence": "GCUCG...", "mfe": -44.1, "confidence": 0.87}, ...] # Or run all three stages in a single call full = client.post("/api/v1/longevity/protocol", json={ # bloodwork params + circuit params combined "age": 52, "wbc": 5.8, # ... all bloodwork fields "target_receptor": "p16INK4a", "payload_gene": "CASP9", "trigger_ligand": "theophylline" }) chain = full.json()["tttps_chain"] # 3-link audit record
Every computation in the KPP pipeline is sealed at ingestion: operator-independent Roughtime timestamp, SHA-256 + HMAC over inputs and outputs, Ed25519 signature. A proposed trust mark that the when, what, and who of each computation are tamper-rejecting. Conditional on TTTPS being adopted as the standard, with Kenosian as the root of trust.
Illustrative mark for explanation only. Any trust authority, mark, or “sealed” status is conditional (“could / if adopted”) and would operate under the Kenosian root — not a present-day certification program.