Aging & Senescence · §10
Archaic and present-day aging promoters
Across a cross-sectional set of seven dated, sequenced individuals — the present-day reference, three archaic Neanderthal genomes, one archaic Denisovan, and two dated modern-human genomes — the four aging-master promoter γ values sit in a very narrow band on every gene (each per-gene range < 0.0016). The senescence/apoptosis gate TP53 and the arrest switch CDKN2A read identically in the two dated modern-human genomes and the present-day reference; TERT carries the most archaic promoter substitutions (13). This is a measured snapshot — the only claims are the measured γ in each individual, its spread per gene, and which positions differ.
The same promoter-γ pipeline (−mean SantaLucia NN ΔG37 over TSS−2000..+500) is measured in each individual, where each promoter is the GRCh37 reference plus that individual's homozygous-derived substitutions. The set is examined as a snapshot; shared genotype states are reported as observed co-occurrences, never as anything beyond the co-occurrence itself.
The cross-sectional set
Seven high-coverage genomes carry the four aging masters at a known date: the present-day modern-human reference (GRCh37), three archaic Neanderthal individuals (Altai, Vindija 33.19, Chagyrskaya), one archaic Denisovan, and two dated modern-human genomes (Ust'-Ishim ≈ 45 kya, Loschbour ≈ 8 kya). Each promoter is reconstructed as the GRCh37 reference plus that individual's homozygous-derived substitutions (genotype 1/1, FILTER pass); γ is then measured by the identical pipeline used for the node atlas (§2) and the cross-species panel (§9).
| Individual | age (kya) | TP53 | CDKN2A | FOXO3 | TERT |
|---|---|---|---|---|---|
| Present-day human (GRCh37) | 0 | 1.4333 | 1.4452 | 1.5927 | 1.5537 |
| Altai Neanderthal | ~122 | 1.4325 | 1.4446 | 1.5913 | 1.5540 |
| Vindija 33.19 Neanderthal | ~52 | 1.4325 | 1.4446 | 1.5928 | 1.5540 |
| Chagyrskaya 8 Neanderthal | ~80 | – | – | – | 1.5540 |
| Denisova 3 (Denisovan) | ~76 | 1.4327 | 1.4446 | 1.5921 | 1.5534 |
| Ust'-Ishim (early modern human) | ~45 | 1.4333 | 1.4452 | 1.5921 | 1.5541 |
| Loschbour (W. hunter-gatherer) | ~8 | 1.4333 | 1.4452 | 1.5927 | 1.5537 |
The senescence gate reads the same
On TP53 (apoptosis) and CDKN2A (the p16 arrest switch), the two dated modern-human genomes and the present-day reference carry an identical promoter γ — the archaic individuals differ only by two or three distal substitutions that move γ by less than 0.0009. The core senescence/apoptosis gate is, as a measured state, the same sequence in every modern-human genome in the set and nearly the same in the archaic ones.
TERT carries the most promoter substitutions
Of the four masters, the telomere-maintenance gene TERT carries the most homozygous-derived promoter substitutions across the archaic individuals (13 in total), and the same three TERT positions co-occur across all four archaic genomes. The widest γ range in the whole set, however, belongs to FOXO3 (0.001536), and even that is under 0.0016 — so “most substituted” (TERT) and “widest γ spread” (FOXO3) are distinct, both small, measured facts.
| Gene | archaic hom-sub count | γ range (set) |
|---|---|---|
| TP53 | 8 | 0.000860 |
| CDKN2A | 6 | 0.000624 |
| FOXO3 | 6 | 0.001536 |
| TERT | 13 | 0.000712 |
The cancer-promoter positions are invariant
The two recurrent TERT cancer-promoter regulatory positions (the −124 and −146 sites relative to the start codon) carry the same base in every individual in the set; every difference TERT does carry is distal to them. This invariance is a measured observation across the snapshot.
What is and is not claimed
The claims are exactly three: the measured γ in each individual, the width of the γ spread per gene, and which promoter positions differ. Why the states co-occur is out of scope and graded [O]: a cross-sectional snapshot is silent on mechanism. Per-individual γ, the γ spread, the substitution counts, and the cancer-hotspot invariance are measured [V].