---
vault_clearance: KETER
halo:
  classification: INTERNAL
  confidence: MEDIUM
  front: "LifeSong — BOOK (literature + methods registry)"
  custodian: "The Architect"
  created: 2026-03-28
  updated: 2026-04-03
  wing: UNASSESSED
  containment: "Bibliography + methods; not a substitute for README / WORLDLINE / BOUNTY"
---

# LifeSong — BOOK

Canonical project literature and methods registry for **18_Project_LifeSong**. Conventions: [`BOOK_Protocol.md`](../BOOK_Protocol.md). Orientation and lab framing: [`README.md`](README.md). Open work: [`BOUNTY_BOARD.md`](BOUNTY_BOARD.md). **Orthodox vs temporal intervention map:** [`FORM.md`](FORM.md). Rows below **arm** FORM §B–E (what to cite when beating constitutive / dose-only baselines).


### Local registry slice (EYE / STAFF / STARS)

| Surface | Pointers |
|---------|----------|
| **EYEs** | Runs: [`README.md`](README.md) / [`WORLDLINE.md`](WORLDLINE.md) (if present). Registry: [`EYE_PROTOCOL.md`](../EYE_PROTOCOL.md) |
| **STAFF** | Runnable tools: [`STAFF_catalogue.json`](../STAFF_catalogue.json) — filter `project_dir` for this folder. |
| **STARS** | This file; rules: [`BOOK_Protocol.md`](../BOOK_Protocol.md). |
| **Audit sheet** | [`LOGGING_AND_REGISTRY_CHECKLIST.md`](../99_Archive/root_reports/2026-04/LOGGING_AND_REGISTRY_CHECKLIST.md) |


---

## 1. Senescence, SASP, and temporal ordering

| ID | Kind | Title / note | Identifier |
|----|------|----------------|------------|
| LS-B1 | Review | Cellular senescence in ageing — mechanisms to therapeutic angles | [`10.1038/s41580-020-00314-w`](https://doi.org/10.1038/s41580-020-00314-w) |
| LS-B2 | Review | SASP as the “dark side” of tumor suppression | [`10.1146/annurev-pathol-121808-102144`](https://doi.org/10.1146/annurev-pathol-121808-102144) |
| LS-B3 | Primary | Oncogene-induced senescence as a tumorigenesis barrier via DNA damage checkpoints | [`10.1038/nature05268`](https://doi.org/10.1038/nature05268) |
| LS-B4 | Primary | Oncogene-induced senescence as a DDR triggered by DNA hyper-replication | [`10.1038/nature05327`](https://doi.org/10.1038/nature05327) |
| LS-B5 | Context | Cross-project **GEM** (senescence timing / cascade order) — do not duplicate here | [`10_Project_GEM/README.md`](../10_Project_GEM/README.md) |

**Use when:** building the **senescence cascade order** narrative, SASP timing, or linking LifeSong claims to GEM’s temporal graph.

---

## 2. Epigenetic maintenance: UHRF1, DNMT1, TRIM28, SETDB1

| ID | Kind | Title / note | Identifier |
|----|------|----------------|------------|
| LS-B10 | Mechanism | UHRF1 reads hemi-methylated DNA and recruits DNMT1 | Search: *Sharif / Bostick UHRF1 DNMT1 maintenance* — add stable DOI when curating chapter |
| LS-B11 | Mechanism | TRIM28 / KAP1 co-repressor complex and heterochromatin | Canonical reviews on KAP1-mediated silencing (add DOI per sub-claim) |
| LS-B12 | Mechanism | SETDB1 / H3K9me3 in stable silencing | Pair with SUV39H1 literature for constitutive vs facultative distinction |

**Use when:** grounding **UHRF1 → DNMT1 → TRIM28 → SETDB1** maintenance logic from README §3 in primary literature.

---

## 3. Reprogramming and partial / cyclic (pulsed) OSKM

| ID | Kind | Title / note | Identifier |
|----|------|----------------|------------|
| LS-B20 | Landmark | Induction of pluripotent stem cells (Yamanaka factors) | [`10.1016/j.cell.2006.07.024`](https://doi.org/10.1016/j.cell.2006.07.024) |
| LS-B21 | Primary | **In vivo** amelioration of age-associated hallmarks by **partial reprogramming** (cyclic OSKM) | [`10.1016/j.cell.2016.11.052`](https://doi.org/10.1016/j.cell.2016.11.052) |
| LS-B22 | Extension | Cyclic / restricted expression in specific lineages (e.g. neurons) — compare duty cycle to README “pulsed” framing | [`10.1038/s42003-024-06328-w`](https://doi.org/10.1038/s42003-024-06328-w) |
| LS-B23 | Translation | Targeted partial reprogramming — healthspan markers in models | [`10.1126/scitranslmed.adg1777`](https://doi.org/10.1126/scitranslmed.adg1777) |

**Use when:** **LS-P2** (pulsed vs constitutive literature scan), OSKM risk/benefit framing, and alignment with **t_L = 9T/2** (LENG) as a *design constraint* not a citation.

---

## 4. Photobiomodulation (PBM): mechanisms, dosing, skepticism

| ID | Kind | Title / note | Identifier |
|----|------|----------------|------------|
| LS-B30 | Review | PBM mechanisms — cytochrome *c* oxidase, NO, evidence critique | [`10.1089/photob.2020.4905`](https://doi.org/10.1089/photob.2020.4905) |
| LS-B31 | Review | Mitochondrial redox signaling in PBM (Hamblin) | [`10.1111/php.12864`](https://doi.org/10.1111/php.12864) |
| LS-B32 | Engineering | README’s **660 nm / 850 nm**, **10 Hz vs 40 Hz** — treat as **hypothesis**; expand this table with wavelength/irradiance studies per **LS-H1–H2** | *(bounty-driven)* |

**Use when:** **LS-H1–H2** (LED matrix + safe exposure envelope), harmonizing with **12** (Orem) and **07** (Command) without over-claiming.

---

## 5. Circadian rhythm, cell cycle, and multi-scale timing

| ID | Kind | Title / note | Identifier |
|----|------|----------------|------------|
| LS-B40 | Concept | Circadian clock and cell-cycle gating (curate primary set per LS-M2) | Add DOIs when M2 narrows organism/context |
| LS-B41 | Methods | Time-course scRNA-seq / pseudotime for **ordering** senescence transitions | GEO / ArrayExpress accession per experiment |

**Use when:** **LS-M1–M4** (temporal graph, synchronization, discretization, verification).

---

## 6. Hormesis, fasting, cold — entry points (high level)

| ID | Kind | Title / note | Identifier |
|----|------|----------------|------------|
| LS-B50 | Survey | Hormesis and stress-response pathways (use as index, not prescription) | Curate per **LS-P3** outcomes |
| LS-B51 | Survey | Time-restricted feeding / fasting-mimicking — circadian and metabolic coupling | Curate per wet-lab **LS-W*** scope |

**Use when:** **LS-P3** (48h fast + cold exposure literature pass) and **LS-W1–W3** wet-lab design.

---

## 7. Open data, code, and hardware baselines

| ID | Kind | Resource | Identifier / note |
|----|------|----------|-------------------|
| LS-D1 | Data | GEO (time-course expression) | [`https://www.ncbi.nlm.nih.gov/geo/`](https://www.ncbi.nlm.nih.gov/geo/) |
| LS-D2 | Data | ArrayExpress | [`https://www.ebi.ac.uk/biostudies/arrayexpress`](https://www.ebi.ac.uk/biostudies/arrayexpress) |
| LS-T1 | Tool | Arduino / embedded PWM for LED timing | Official docs + project firmware under **LS-H*** |
| LS-T2 | Safety | Laser / LED exposure standards (regional) | IEC / FDA / EU MDR pointers — add exact refs when **LS-H2** locks geography |

---

## 8. STARS — US and international anchors

**Trial registries and literature** alongside §7 (GEO / ArrayExpress). Use for human-subject and regulatory context.

### How to read STARS (context)

**STARS** (`LS-S*`) are **regulatory and literature portals** for human-subject and intervention framing. **§§1–7** hold **biology and methods** DOIs; STARS do **not** replace primary papers for senescence or PBM mechanisms.

| ID | What this STAR denotes | Typical use in this BOOK | Not / caveats |
|----|-------------------------|--------------------------|---------------|
| LS-S1 | ClinicalTrials.gov | **Trial registration** lookup | Registry entry ≠ peer-reviewed outcome paper. |
| LS-S2 | CTIS | **EU trial** workflow | Policy and registration; read national rules for site. |
| LS-S3 | PubMed | **Biomedical** abstract index | Abstracts are not full methods. |
| LS-S4 | DailyMed | **FDA label text** via NLM | Labels are regulatory, not off-label practice guidance. |

| ID | Region | Kind | Note | Identifier |
|----|--------|------|------|------------|
| LS-S1 | US | Clinical trials registry | ClinicalTrials.gov (NIH) | [clinicaltrials.gov](https://clinicaltrials.gov/) |
| LS-S2 | EU | EU clinical trials | CTIS (European Medicines Agency workflow) | [euclinicaltrials.eu](https://euclinicaltrials.eu/) |
| LS-S3 | US | Biomedical literature | PubMed | [pubmed.ncbi.nlm.nih.gov](https://pubmed.ncbi.nlm.nih.gov/) |
| LS-S4 | Multilateral | Drug information (US NIH) | DailyMed (FDA-provided labels via NLM) | [dailymed.nlm.nih.gov](https://dailymed.nlm.nih.gov/) |

---

## 9. Bounty → start here

| Bounty | Start with |
|--------|------------|
| **Orthodox cultivator (board)** | [`FORM.md`](FORM.md) §A–B, then cite BOOK §§1–4 |
| **LS-M1–M4** | §5 → §1 → GEM README |
| **LS-P2** | §3 |
| **LS-P1, LS-P4** | §1, §5 |
| **LS-P3** | §6 |
| **LS-H1–H2** | §7, §4 |
| **LS-W1–W3** | §6, §3 (safety), §1 |

---

*BOOK revision: 2026-04-03 — §8 STARS context table; paired with [`FORM.md`](FORM.md).*