Senescence, the SASP and Immunosurveillance
A senescent cell is arrested, damaged and apoptosis-resistant \u2014 three properties, and the third is the one that matters. Arrest alone is quiescence. Arrest with persistent DNA damage is senescence. Arrest with damage and a BCL-2 dependency that blocks apoptosis is why these cells accumulate rather than dying, and why the entire senolytic strategy consists of removing that dependency. What they do while they sit there is the SASP: a secretome of IL-6, IL-1\u03b1, matrix metalloproteinases and chemokines that remodels the tissue, recruits myeloid cells, and induces senescence in neighbouring cells \u2014 so a local event becomes a tissue-level one. The immune system is supposed to clear them, and largely does in youth. This map is about why that fails. Click any protein for the matching Assay Genie In Vivo antibody or ELISA kit.
Three properties, not one, and the markers do not agree. Senescence is routinely identified by a single stain, and it should not be. SA-\u03b2-galactosidase is the oldest marker and reports lysosomal mass at pH 6 \u2014 which rises in senescence, and also in confluent and serum-starved cultures. p21 rises early and p16 sustains, so a p16-only panel misses the early state. Lamin B1 is one of the few markers that goes down rather than up, which makes it unusually hard to produce artefactually, and its loss is mechanistically interesting rather than merely diagnostic: it is what lets cytoplasmic chromatin fragments escape the nucleus. And \u03b3H2AX is what separates senescence from quiescence, because a quiescent cell is arrested and undamaged while a senescent one is arrested and carries persistent unrepaired breaks. Any figure resting on one of these alone is weaker than it looks.
The SASP is self-sustaining, and IL-1\u03b1 sits at the top of it. Membrane-bound IL-1\u03b1 on the senescent cell drives the IL-6 and CXCL8 arms, and IL-6 then reinforces the programme in the cell that secreted it. That autocrine loop is why the secretome persists rather than resolving, and it is why IL-1\u03b1 is the highest-leverage single intervention on the secretory band \u2014 blocking it collapses much of the secretome at once rather than trimming one component. The matrix arm does something different again: MMP-3 and MMP-9 degrade basement membrane, which is one of the routes by which senescent stromal cells make neighbouring epithelium more invasive. PAI-1 is both a SASP component and a driver of senescence in its own right, a feed-forward node worth knowing about before interpreting any SERPINE1 result.
Visible and protected at the same time. Senescent cells induce MICA, MICB and ULBP2, which NKG2D reads \u2014 the same recognition system that handles transformed cells, which is why NK cells do both jobs. But they also retain CD47, and they raise PD-L1 and CD155. A senescent cell can therefore be simultaneously visible to an NK cell, protected from a macrophage, and able to switch off the T cell that arrives. That combination is the most economical account of why clearance is incomplete and why it gets worse with age. There is an escape route on the ligand side too: MICA is shed, and soluble MICA occupies NKG2D without engaging it \u2014 turning a visibility signal into a decoy, which is why measuring soluble rather than total MICA is usually the question worth asking.
The In Vivo tie-in, and where this map is thin. 12 of the 36 nodes carry a functional-grade antibody, and all twelve are on the immune side rather than on the senescent cell. That is the shape of the field as much as of the catalogue. What it supports is the experiment the surveillance literature is actually built on: NK1.1, CD8 (Ly-2), CD4 (GK1.5), CSF-1R and CD68 make a complete clearance-depletion panel, so removing an effector and watching senescent burden rise is fully available \u2014 and the CD4 arm matters, since CD4 depletion alone is enough to let premalignant senescent hepatocytes persist in the liver. PD-L1 (10F.9G2) and CD155 are both blockable, which makes the escape arm testable rather than assertable, and IFN-\u03b3 (XMG1.2), TNF, IL-1\u03b2, TGF-\u03b2 and IL-10 complete the cytokine set. Stated plainly, the senescent cell itself is entirely a read-out here: p16, \u03b3H2AX, lamin B1, SA-\u03b2-gal, BCL-2, uPAR, GDF15, IL-6, CXCL8, the MMPs, PAI-1, CCL2, CXCL1, MICA, MICB, ULBP2, perforin and granzyme B are ELISA only; p21 and p53 are research grade; and NKG2D, CD47 and IL-1\u03b1 are biosimilar. One node is worth flagging for a different reason: uPAR is broadly induced on the senescent surface and is the target of the first senolytic CAR-T constructs, which makes it the most therapeutically live marker here \u2014 surface accessibility being precisely what senescence markers usually lack. A last assay caution: TNF is stocked ultra-low endotoxin, and senescence assays run long, so contaminating endotoxin accumulates in a way it does not in a four-hour experiment. For research use only; not for use in diagnostic or therapeutic procedures.
Every protein node links to a product — ELISA kit, In Vivo antibody or research antibody.