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Inflammaging

Inflammaging is a science 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 Inflammaging rather than just read about it. In short: Inflammaging (also known as inflamm-aging or inflamm-ageing) is a chronic, sterile, low-grade inflammation that develops with advanced age, in the absence of overt infection, and may contribute to clinical manifestations of other age-related pathologies. Inflammaging is thought to be caused by a loss of control over systemic inflammation resulting in chronic overstimulation of the innate immune system.

Inflammaging — main illustration
Inflammaging — illustration

Key takeaways

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

Reference excerpt

Inflammaging (also known as inflamm-aging or inflamm-ageing) is a chronic, sterile, low-grade inflammation that develops with advanced age, in the absence of overt infection, and may contribute to clinical manifestations of other age-related pathologies. Inflammaging is thought to be caused by a loss of control over systemic inflammation resulting in chronic overstimulation of the innate immune system. Inflammaging is a significant risk factor in mortality and morbidity in aged individuals. Inflammation is essential to protect against viral and bacterial infection, as well as noxious stimuli. It is an integral part of the healing process, though prolonged inflammation can be detrimental. The network dynamics of inflammation change with age, and factors such as genes, lifestyle, and environment contribute to these changes. Current research studying inflammaging is focused on understanding the interaction of dynamic molecular pathways underlying both aging and inflammation and how they change with chronological age.

Characteristics Fine control and modulation of the immune system response becomes fragile and less precise with age, as seen with other bodily systems. Remodeling of the immune system in the elderly is thought to be characterized by an inability to control systemic inflammation. With age, the number of lymphocytes being produced decreases, and the composition and quality of the mature lymphocyte pool changes. While the effectiveness of adaptive immune system declines, innate immune mechanisms become overactive and less precise, leading to an increase in pro-inflammatory phenotypes that contributes to "inflammaging." The secretome of senescent mesenchymal stem and stromal cells (MSCs) exhibits immunomodulatory effects and serves as a driver in inflammaging-related diseases. All together, this contribues to a less efficient immune system response to pathogens and chronic, systemic inflammatory phenotypes.

Causes Inflammaging is a complex and systemic issue, likely a result of several factors.

Inflammasome activation

Over-activation of the inflammasome is one mechanism contributing to inflammaging. The inflammasome is a multi-protein complex consisting of a sensor, an adapter, and an effector, that when activated, modulates caspases which cleave cytokines and result in an inflammatory signaling response. Receptors present on the cell surface act as sensors for the detection of damage and pathogens. When activated, this system can go on to elicit pro-inflammatory cytokine secretion and sometimes cell death. Pro-inflammatory cytokines secretion acts as the effector or the response to such stimuli. Stimuli that can fuel inflammasome assembly include pathogen-associated molecular patterns (PAMPS), damage associated molecular patterns (DAMPS), nutrients, and the microbiota. These various self, non-self, and quasi self molecules are recognized by receptors of innate immune cells, whose promiscuity allows for many different signals to lead to activation and consequently to inflammation. Examples of stimuli that act as PAMPS include viral and bacterial infection, such as cytomegalovirus and periodontitis, respectively. Examples of DAMPS include misfolded and oxidized proteins, cell debris, and self nucleic acids.

Generation of reactive oxygen species In addition to inflammasome activation, with age, cellular components accumulate reactive oxygen species (ROS). These free radicals can damage DNA, lipid, and protein and is able to drive cellular senescence. This is accompanied by a loss in efficiency of DNA damage repair mechanisms. This results in pro-inflammatory cytokine secretion, which contributes to low grade, chronic inflammation in the absence of pathogen or damage, but rather in response to damaged self molecules like oxidized nucleotides.

SASP phenotype Senescent cell populations increase with age and secrete a pro-inflammatory cocktail of chemicals, a condition known as senescence-associated secretory phenotype (SASP). Cells with the SASP are characterized by being in cell cycle arrest, releasing inflammatory factors, and possessing a particular morphology. These cells promote tissue degeneration and are able to spread to other regions by way of the inflammatory secretory molecules released. This contributes to inflammaging as inflammatory secretion contributes to innate immune activation and exhaustion.

Functional decline in autophagy and mitophagy Another contribution to inflammaging is a decline in effective autophagy and mitophagy capacity. This is an essential process for cellular housekeeping that prevents protein aggregation and accumulation of damaged mitochondria that produce large quantities of reactive oxygen species. A loss of effective autophagic processes leads to aggregation of damaged proteins. As inflammasome precision declines with age, these aggregates, normally degraded, can be recognizes as a pathogen and lead to an inflammatory response. This contributes to inflammaging and is also involved in many neurodegenerative diseases as well.

Other factors Other possible factors that may lead to inflamm-aging include insufficient sleep, overnutrition, sensory overload, physical inactivity, altered gut microbiome, impaired intestinal epithelial barrier, and chronic stress occurring in any stage of the individual's life. Cytokines with inflammatory properties can also be secreted by fat tissue.

Biomarkers of inflammaging

Cytokines are currently used as biomarkers of inflammaging as they are indicative of inflammation and play a large role in the regulation of pro and anti-inflammatory immune regulation. Cytokines are small proteins that are secreted by many cell types that are very relevant in the study of aging and longevity. Aging studies show that a healthy balance of pro and anti-inflammatory cytokine secretion is associated with successful aging whereas dysregulation of this system results in inflammaging, poor aging phenotypes, and other aging-related diseases. Currently, levels of TNF, IL-6 and IL-1 can be used as inflammatory biomarkers that indicate frailty, an altered immune system, functional decline and mortality associated with inflammaging . Biomarkers of immuno-senescence also exist and involved changes to T cells, CD4/CD8 ratios as well as the SASP phenotype. Altogether, these biomarkers may not be translationally relevant to clinical outcomes. The generation of more reliable biomarkers of inflammation and aging is of interest in current research.

… excerpt ends here. Continue reading the full article.

Illustrations

Inflammaging: Factors involved in inflammaging: Aging leads to perturbations in cellular homeostasis leading to inflammaging that results in pro-inflammatory cytokine secretion.[1]
Factors involved in inflammaging: Aging leads to perturbations in cellular homeostasis leading to inflammaging that results in pro-inflammatory cytokine secretion.[1]
Inflammaging: Inflammasome activation and assembly: Release of ROS and pro-inflammatory cytokine secretion in response to inflammasome assembly after DAMP / PAMP binding
Inflammasome activation and assembly: Release of ROS and pro-inflammatory cytokine secretion in response to inflammasome assembly after DAMP / PAMP binding
Inflammaging: TNF mediated cell survival and death pathway: TNF binding to receptors induces apoptosis and necrosis through various signaling pathways.
TNF mediated cell survival and death pathway: TNF binding to receptors induces apoptosis and necrosis through various signaling pathways.
Inflammaging: Crystal protein structure of tumor necrosis factor.
Crystal protein structure of tumor necrosis factor.
Inflammaging: Cytokine storm induced by SARS-CoV2 infection: Infection by SARS-COV 2 leads to COVID-19 Infection resulting in activation of inflammatory phenotypes by cell types in both the central nervous system and within the immune system network
Cytokine storm induced by SARS-CoV2 infection: Infection by SARS-COV 2 leads to COVID-19 Infection resulting in activation of inflammatory phenotypes by cell types in both the central nervous system and within the immune system network

Worked examples

Example 1 — a first encounter with Inflammaging

Start with the simplest possible case. Write down what Inflammaging claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, 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 Inflammaging 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 Inflammaging 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 Inflammaging

In research
Inflammaging appears in science 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 Inflammaging 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
Inflammaging is common in secondary-school and first-year university syllabi. It links to neighbouring topics Ageing, Biogerontology, Inflammations, so understanding it makes those chapters shorter.
In everyday life
Look for Inflammaging 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 Inflammaging in 20 minutes

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

Frequently asked questions

What is Inflammaging in simple terms?

Inflammaging (also known as inflamm-aging or inflamm-ageing) is a chronic, sterile, low-grade inflammation that develops with advanced age, in the absence of overt infection, and may contribute to clinical manifestations of other age-related pathologies. Inflammaging is thought to be caused by a lo…

Why does Inflammaging matter?

Because it connects several science 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 Inflammaging?

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 Inflammaging.

Tags

  • Ageing
  • Biogerontology
  • Inflammations
  • Old age

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