biology

Senescence-associated secretory phenotype

Senescence-associated secretory phenotype is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Senescence-associated secretory phenotype rather than just read about it. In short: Senescence-associated secretory phenotype (SASP) is a phenotype associated with senescent cells wherein those cells secrete high levels of inflammatory cytokines, immune modulators, growth factors, and proteases. SASP may also consist of exosomes and ectosomes containing enzymes, microRNA, DNA fragments, chemokines, and other bioactive factors.

Key takeaways

Senescence-associated secretory phenotype belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Senescence-associated secretory phenotype to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Senescence-associated secretory phenotype from memory before moving on to harder problems.

Reference excerpt

Senescence-associated secretory phenotype (SASP) is a phenotype associated with senescent cells wherein those cells secrete high levels of inflammatory cytokines, immune modulators, growth factors, and proteases. SASP may also consist of exosomes and ectosomes containing enzymes, microRNA, DNA fragments, chemokines, and other bioactive factors. Soluble urokinase plasminogen activator surface receptor is part of SASP, and has been used to identify senescent cells for senolytic therapy. Initially, SASP is immunosuppressive (characterized by TGF-β1 and TGF-β3) and profibrotic, but progresses to become proinflammatory (characterized by IL-1β, IL-6 and IL-8) and fibrolytic. SASP is the primary cause of the detrimental effects of senescent cells. SASP is heterogenous, with the exact composition dependent upon the senescent-cell inducer and the cell type. Interleukin 12 (IL-12) and Interleukin 10 (IL-10) are increased more than 200-fold in replicative senescence in contrast to stress-induced senescence or proteosome-inhibited senescence where the increases are about 30-fold or less. Tumor necrosis factor (TNF) is increased 32-fold in stress-induced senescence, 8-fold in replicative senescence, and only slightly in proteosome-inhibited senescence. Interleukin 6 (IL-6) and interleukin 8 (IL-8) are the most conserved and robust features of SASP. But some SASP components are anti-inflammatory. Senescence and SASP can also occur in post-mitotic cells, notably neurons. The SASP in senescent neurons can vary according to cell type, the initiator of senescence, and the stage of senescence. An online SASP Atlas serves as a guide to the various types of SASP. SASP is one of the three main features of senescent cells, the other two features being arrested cell growth, and resistance to apoptosis. SASP factors can include the anti-apoptotic protein Bcl-xL, but growth arrest and SASP production are independently regulated. Although SASP from senescent cells can kill neighboring normal cells, the apoptosis-resistance of senescent cells protects those cells from SASP.

History The concept was first established in the late eighties by Dr. Michael D. West. Dr. West has, through collaboration with Geron, Inc. later funded work in Judith Campisi's lab to create a cell-based screen for drugs that inhibit the phenotype. Campisi subsequently named the phenotype SASP.

Causes SASP expression is induced by a number of transcription factors, including MLL1 (KMT2A), C/EBPβ, and NF-κB. NF-κB and the enzyme CD38 are mutually activating. NF-κB is expressed as a result of inhibition of autophagy-mediated degradation of the transcription factor GATA4. GATA4 is activated by the DNA damage response factors, which induce cellular senescence. SASP is both a promoter of DNA damage response and a consequence of DNA damage response, in an autocrine and paracrine manner. Aberrant oncogenes, DNA damage, and oxidative stress induce mitogen-activated protein kinases, which are the upstream regulators of NF-κB. Demethylation of DNA packaging protein Histone H3 (H3K27me3) can lead to up-regulation of genes controlling SASP. mTOR (mammalian target of rapamycin) is also a key initiator of SASP. Interleukin 1 alpha (IL1A) is found on the surface of senescent cells, where it contributes to the production of SASP factors due to a positive feedback loop with NF-κB. Translation of mRNA for IL1A is highly dependent upon mTOR activity. mTOR activity increases levels of IL1A, mediated by MAPKAPK2. mTOR inhibition of ZFP36L1 prevents this protein from degrading transcripts of numerous components of SASP factors. Inhibition of mTOR supports autophagy, which can generate SASP components. Ribosomal DNA (rDNA) is more vulnerable to DNA damage than DNA elsewhere in the genome such that rDNA instability can lead to cellular senescence, and thus to SASP The high-mobility group proteins (HMGA) can induce senescence and SASP in a p53-dependent manner. Activation of the retrotransposon LINE1 can result in cytosolic DNA that activates the cGAS–STING cytosolic DNA sensing pathway upregulating SASP by induction of interferon type I. cGAS is essential for induction of cellular senescence by DNA damage. SASP secretion can also be initiated by the microRNAs miR-146 a/b. Senescent cells release mitochondrial double-stranded RNA (mt-dsRNA) into the cytosol driving the SASP via RIGI/MDA5/MAVS/MFN1. Moreover, senescent cells are hypersensitive to mt-dsRNA-driven inflammation due to reduced levels of PNPT1 and ADAR1.

Pathology

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Worked examples

Example 1 — a first encounter with Senescence-associated secretory phenotype

Start with the simplest possible case. Write down what Senescence-associated secretory phenotype claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Senescence-associated secretory phenotype before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Senescence-associated secretory phenotype ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Senescence-associated secretory phenotype

In research: Senescence-associated secretory phenotype appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Senescence-associated secretory phenotype in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Senescence-associated secretory phenotype is common in secondary-school and first-year university syllabi. It links to neighbouring topics Cellular senescence, so understanding it makes those chapters shorter.
In everyday life: Look for Senescence-associated secretory phenotype outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Senescence-associated secretory phenotype in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Senescence-associated secretory phenotype means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Senescence-associated secretory phenotype out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Senescence-associated secretory phenotype in simple terms?

Why does Senescence-associated secretory phenotype matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Senescence-associated secretory phenotype?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Senescence-associated secretory phenotype.