Biology of Aging

Adult stem cells (also called somatic stem cells) are undifferentiated cells that live in specific tissue 'niches'. Their job is to maintain and repair that tissue throughout…

Advanced glycation end-products (AGEs) are stable, often crosslinked compounds. They form when sugars react with your proteins, lipids, or DNA over time. They build up in…

The AGE-RAGE axis is an inflammation-driving signaling loop. It starts when advanced glycation end products (AGEs), and other ligands, bind a receptor called RAGE (coded by the…

AMPK is your cell's low-fuel warning light. Its full name is AMP-activated protein kinase, and it switches on when energy runs low, when AMP and ADP rise relative to ATP (the…

Angiogenesis is the growth of new blood vessels from existing capillaries. The main driver is VEGF-A (vascular endothelial growth factor-A), a protein that binds two receptors…

Apoptosis is a tightly controlled form of programmed cell death. The cell is taken apart in an orderly way, by enzymes called caspases. It usually does not spark inflammation,…

Atherosclerosis is the slow, inflammation-driven clogging of your medium and large arteries. It starts when cholesterol-carrying particles (ApoB-containing lipoproteins, mainly…

Autophagy is your body's recycling program for worn-out cell parts. The name means "self-eating": a cell wraps damaged proteins and broken organelles in a double-membrane bag (an…

Beclin-1 (made by the BECN1 gene) is a core part of the machinery that starts autophagy in your cells. It belongs to a complex (the class III PI3K, or VPS34, complex) that…

Biomolecular condensates are membraneless 'organelles' that form by liquid-liquid phase separation (LLPS). That is the spontaneous demixing of proteins and RNAs into a dense…

Cardiolipin (CL) is a special double phospholipid. It is found almost only in the inner membrane of your mitochondria. It makes up roughly 15 to 20% of that membrane's lipid. Its…

Cathepsins are a family of protein-chewing enzymes (proteases) that work inside your lysosomes, the cell's acidic recycling chambers. Most are cysteine proteases (cathepsins B,…

CD38 is a membrane glycoprotein with two enzyme jobs: it breaks down NAD+ and it cyclizes ADP-ribose. It shows up on many cells, but most heavily on immune cells. It splits NAD+…

Cellular reprogramming is the lab process of converting one cell type into another. Most often, it turns a specialized body cell back into a pluripotent stem cell. It does this…

Cellular senescence is what happens when a cell stops dividing for good but refuses to die. Stress sets it off: DNA damage, frayed telomeres, a switched-on cancer gene, or…

The cGAS-STING pathway is one of your cells' built-in alarms for danger DNA. The sensor, cGAS (cyclic GMP-AMP synthase), detects double-stranded DNA floating loose in the cell's…

Chaperone-mediated autophagy (CMA) is a precise way your cells recycle individual proteins. Unlike bulk autophagy, it does not wrap cargo in a vesicle. Instead, it ferries one…

Chromatin is the bundle of DNA, histone proteins, and other proteins that packs your genome into the nucleus. Its basic unit is the nucleosome. It can be packed tight (as…

Cuproptosis is a form of controlled cell death driven by copper. It is distinct from other death programs like apoptosis, ferroptosis, necroptosis, and pyroptosis. Here is how it…

DNA damage is any chemical or structural change to your genome. It includes base modifications, single- and double-strand breaks, and crosslinks. It comes from reactive oxygen…

DNA methylation is one of the main ways your cells control which genes are switched on, without changing the DNA code itself. Enzymes called DNA methyltransferases stick small…

DNA methyltransferases (DNMTs) are the enzymes that add methyl tags to your DNA. They move a methyl group from SAM (S-adenosylmethionine) onto a cytosine base, mostly at 'CpG'…

Elastin is the matrix protein that lets your tissues stretch and snap back, especially your artery walls, lungs, and skin. Here is the catch: your body lays down almost all of…

The electron transport chain (ETC) is a set of four protein complexes in your inner mitochondrial membrane. They are Complex I (NADH:ubiquinone oxidoreductase), Complex II…

Endothelial dysfunction is when the thin inner lining of your blood vessels (the endothelium) stops keeping them healthy. The classic problem: it makes too little usable nitric…

Epigenetic alterations are age-related changes in how your genes are switched on and off, without any change to the DNA code itself. They include shifts in DNA methylation, in…

ER stress happens when your cells' protein-folding factory gets overwhelmed. The endoplasmic reticulum (ER) folds, modifies, and quality-checks proteins headed for secretion or…

The extracellular matrix (ECM) is the protein-and-sugar scaffold that holds your tissues together. It also passes chemical and mechanical signals to the cells living in it. As…

Extracellular vesicles (EVs) are tiny membrane bubbles that nearly every cell releases. They come in rough size classes: exosomes (30 to 150 nm, born inside the cell),…

Ferroptosis is a controlled form of cell death driven by iron and runaway fat oxidation. Iron lets lipid peroxides (oxidized fats) build to lethal levels, which sets it apart…

FGF21 (fibroblast growth factor 21) is a hormone, mostly made by your liver. It is released in response to fasting, low protein intake, and mitochondrial stress. It acts on…

Fibrosis is scarring gone overboard. When a tissue is injured, inflamed, or full of senescent cells, specialized cells called myofibroblasts lay down too much connective tissue…

FOXO proteins (short for Forkhead box O) are key switches in your insulin/IGF-1 pathway. When insulin and IGF-1 signals run low, FOXO enters the nucleus. There it turns on…

Free radicals are atoms or molecules with one or more unpaired electrons. That makes them highly reactive. They come from your normal metabolism, your immune activity, and…

GDF11 (growth differentiation factor 11) is a signaling protein in the TGF-β family. In the embryo, it has a well-established job: helping pattern the body axis and organs, by…

GDF15 (growth differentiation factor 15), also called MIC-1, is an unusual member of the TGF-β protein family. Normally it sits at low levels. But it shoots up under…

Genomic instability is the slow build-up of damage to your DNA, both in the nucleus and in the mitochondria. It includes point mutations, reshuffled chromosomes, copy-number…

Glutathione (GSH) is your cells' main built-in antioxidant. It is a small molecule (a thiol) that your body makes in two energy-using steps from three amino acids: glutamate,…

Glycation is the non-enzymatic sticking of sugars, like glucose or fructose, onto your proteins, fats, or DNA. Through the Maillard reaction, it first makes unstable Schiff…

The Hallmarks of Aging are a checklist of the main things that go wrong in your body as you age. Biologists Lopez-Otin and colleagues came up with the framework. The 2023 update…

The Hayflick limit is the most times a normal human body cell can divide in culture, typically 40 to 60 times, before it stops and enters replicative senescence. Leonard Hayflick…

Heat shock proteins (HSPs) are a family of highly conserved 'molecular chaperones'. They are named for being induced by heat, but they are active under many kinds of stress. They…

Hematopoietic stem cells (HSCs) are the rare master cells in your bone marrow that make blood for your whole life. They do it by dividing in a way that both renews themselves and…

Heterochromatin is the tightly packed, switched-off part of your DNA. It is held shut by chemical marks on the histone proteins (like H3K9me2/3 and H3K27me3). Helpers such as HP1…

HIF-1α is the part of a master switch your cells use to respond to low oxygen. It is the oxygen-sensitive half of a transcription factor called HIF-1 (one half, HIF-1α, plus a…

The Hippo pathway is an ancient kinase cascade that controls organ size, tissue balance, and stem-cell activity. Its core kinases (MST1/2 and LATS1/2) work by tagging two…

Histone modifications are reversible chemical changes to histone proteins. (Your DNA wraps around those proteins.) They include acetylation, methylation, phosphorylation, and…

Hormesis is the idea that a little bit of a stressor can be good for you, even though a lot of it would hurt you (scientists call this a biphasic dose-response). The dose makes…

IGF-1 signaling is the cascade that fires when insulin-like growth factor 1 binds its receptor in your cells. It switches on two parallel branches, PI3K/AKT and MAPK/ERK.…

Inflammaging is the chronic, low-grade, sterile inflammation that builds up as you age. It happens even without any infection. It shows up as raised baseline levels of…

The insulin/IGF-1 pathway (often shortened to IIS) is one of your body's main nutrient sensors. When insulin and IGF-1 (a growth hormone) latch onto their receptors, they switch…

The integrated stress response (ISR) is a built-in alarm system your cells use to cope with trouble. No matter the threat, it funnels down to one move: switching off a key…

Induced pluripotent stem cells (iPSCs) are adult body cells reprogrammed back into a flexible, pluripotent state. Researchers do it with factors called OSKM (Oct4, Sox2, Klf4,…

The JAK-STAT pathway is a fast signaling relay from your cell surface to its nucleus. (JAK = Janus kinase; STAT = signal transducer and activator of transcription.) Many…

Klotho (here meaning alpha-Klotho, distinct from beta-Klotho) is a membrane-spanning protein, made mostly in your kidney and brain. After it is cleaved, it also circulates as a…

Lamin A is a structural protein (an intermediate filament) and a major part of the nuclear lamina, the mesh just under your cell's inner nuclear membrane. It is essential for…

LC3 lipidation is a key step in building an autophagosome (the autophagy 'garbage bag'). It attaches the autophagy protein LC3 to a membrane fat (phosphatidylethanolamine, or…

LINE-1 (long interspersed nuclear element-1, or L1) is a type of 'jumping gene' (a retrotransposon) that makes up roughly 17% of your genome. It encodes two proteins (ORF1p and…

Lipid peroxidation is a chain-reaction form of fat damage. It hits the polyunsaturated fats (PUFAs) in your cell membranes, lipoproteins, and fat droplets. It kicks off when a…

Lipofuscin is the 'age pigment', a yellow-brown gunk that builds up inside your cells. It is made of cross-linked, oxidized proteins, damaged fats, sugar add-ons, and reactive…

Loss of proteostasis is one of the established hallmarks of aging. The word 'proteostasis' means protein balance. This hallmark is the age-related decline of your protein…

The lysosome is a membrane-bound compartment inside your cells. It is filled with acidic digestive enzymes (hydrolases). It breaks down proteins, fats, nucleic acids, and…

Methylglyoxal (MGO) is a highly reactive, damaging molecule (a dicarbonyl) that your cells make as an accidental byproduct of glycolysis (sugar-burning). It is the main…

Mitochondrial biogenesis is how your cells build more mitochondria, the tiny power plants that make your energy. To pull it off, the cell has to coordinate genes from two places…

Mitochondrial DNA (mtDNA) is the small, circular genome inside your mitochondria. It is about 16,569 base pairs, present in many copies per cell. It encodes 13 essential parts of…

Mitochondrial dynamics is the constant cycle of fission (splitting) and fusion (merging) that reshapes your mitochondrial network as metabolic needs and stress change. Fission is…

Mitochondrial dysfunction means your cells' power plants are running poorly. (Mitochondria are those power plants.) It shows up in several ways. The cells make less ATP energy.…

The mitochondrial unfolded protein response (mtUPR) is a stress-signaling pathway inside your mitochondria. It fires when misfolded or clumped proteins overwhelm the…

Mitophagy is your cells' way of recycling broken mitochondria. It is a selective form of autophagy. It targets damaged or 'depolarized' mitochondria. It then ships them to the…

mTOR is a master growth switch inside your cells. The name stands for "mechanistic target of rapamycin," and it is an enzyme (a serine/threonine kinase) that reads the signals…

mTOR is a master growth-control kinase, and it works inside two distinct teams. mTORC1 is built around a scaffold protein called Raptor. mTORC2 is built around a different one,…

Myostatin, also called GDF8, is a secreted protein in the TGF-β family, and the main brake on your muscle growth. McPherron, Lawler, and Lee first characterized it in 1997. Your…

NAD+ is a helper molecule (a coenzyme) your cells cannot make energy without. It carries electrons during metabolism. It is also the fuel for three groups of enzymes: sirtuins,…

NADH is the reduced form of NAD+. Your cells make it when NAD+ accepts electrons, during glycolysis, the citric acid cycle, and fatty-acid oxidation. NADH then delivers those…

NAMPT (nicotinamide phosphoribosyltransferase) is the rate-limiting enzyme of the NAD+ 'salvage pathway'. That is the main route your cells use to remake NAD+ from nicotinamide…

Necroptosis is a controlled but messy way for your cells to die. Unlike tidy apoptosis, the cell bursts open, but it still follows a defined molecular script. The key players are…

NF-κB is a family of 'master switch' transcription factors for inflammation. (Its full name is nuclear factor kappa-light-chain-enhancer of activated B cells.) The family has…

Nitric oxide (NO) is a gas that acts as a signaling molecule. Your blood-vessel lining (endothelium) makes it with an enzyme called eNOS (NOS3), converting L-arginine and oxygen…

The NLRP3 inflammasome is a multi-protein alarm complex in your cells. It is built from three parts: a sensor (NLRP3), an adaptor (ASC), and pro-caspase-1. It assembles in…

You have probably heard that sugar can stiffen collagen (those are AGE crosslinks). But there is a second, completely different kind your body makes on purpose. An enzyme called…

Notch signaling is a cell-to-cell communication system that decides cell fates and keeps tissues balanced. It works only by direct contact between touching cells. Here is the…

NRF2 is your cells' emergency chief for oxidative stress. It is a transcription factor (a protein that switches genes on) that, once activated, turns on a whole defense program:…

Nuclear pore complex (NPC) aging is the slow breakdown of the giant protein gates in your cell's nucleus over time. These pores (about 120 MDa each) perforate the nuclear…

One-carbon metabolism is a linked set of chemical cycles (the folate and methionine cycles) that shuttle single carbon atoms around your cells. Your body uses those carbons to…

Oxidative stress is an imbalance in your cells. On one side are reactive oxygen species (ROS). On the other are your body's antioxidant defenses. When ROS outpace the defenses,…

p16INK4a is a brake on the cell cycle (a cyclin-dependent kinase inhibitor), made from the CDKN2A locus. It blocks CDK4/6, which halts the cell cycle and locks the cell into…

p21, encoded by the CDKN1A gene (cyclin-dependent kinase inhibitor 1A), is a strong brake on the cell cycle. It blocks cyclin-CDK complexes, especially CDK2. That enforces a…

p38 MAPK (p38 mitogen-activated protein kinase) is a stress-activated enzyme. It has four versions (α, β, γ, δ), with p38α the main, best-studied one. Upstream kinases (MKK3 and…

p53 is a tumor-suppressor protein, made from the TP53 gene. It acts as a master switch (a transcription factor) in your cell's response to stress, such as DNA damage, low oxygen,…

p62 (made by the SQSTM1 gene) is a multitasking 'adaptor' protein, best known as a selective receptor for autophagy, your cells' recycling system. It grabs cargo that has been…

Parkin, encoded by the PRKN gene (formerly PARK2), is an E3 ubiquitin ligase. It is a RING-between-RING type. It sits at the center of mitochondrial quality control. In the…

PARP1 (poly(ADP-ribose) polymerase 1) is a nuclear enzyme. It is a central sensor of DNA damage, especially single-strand breaks. When activated, it cleaves NAD+. Then it…

Partial reprogramming tries to rejuvenate your cells without erasing what they are. It uses brief or low-dose 'Yamanaka factors' to roll cells back toward a younger state. But it…

PGC-1α is the master switch for building new mitochondria, your cells' power plants. It is a 'co-activator', meaning it cannot grab DNA itself; instead it teams up with other…

The PI3K/AKT pathway is a central signaling line inside your cells. It is switched on by receptor tyrosine kinases (including the insulin and IGF-1 receptors), by…

PINK1 (PTEN-induced kinase 1) is a kinase that sits in your mitochondria and acts as a damage sensor. In a healthy mitochondrion, with an intact membrane voltage, PINK1 is pulled…

Protein carbonylation is a permanent kind of oxidative damage to your proteins. It happens when carbonyl groups (aldehydes or ketones) get stuck onto a protein's side chains,…

Protein crosslinks are covalent bonds that join two protein molecules, or two parts of the same protein. They can form on purpose, by enzymes (as in collagen maturing). Or they…

Proteostasis (short for protein homeostasis) is the network that keeps your proteins working. It controls the whole life cycle of a protein: making it, folding it, moving it, and…

Pyroptosis is a highly inflammatory form of programmed cell death. The executioners are 'gasdermin' proteins, especially gasdermin D (GSDMD). Inflammatory caspases cut GSDMD. (In…

Reactive oxygen species (ROS) are unstable molecules that contain oxygen. The main ones are superoxide, hydrogen peroxide, and hydroxyl radicals. Your cells make them in several…

Regenerative medicine builds therapies to repair, replace, or regrow damaged cells, tissues, and organs. Its tools are varied. They include stem-cell transplants, tissue…

S6K1 is a key worker downstream of mTORC1, your cells' growth switch. Its full name is ribosomal protein S6 kinase 1 (gene RPS6KB1). It is an enzyme that drives protein-making.…

SA-β-Gal (senescence-associated β-galactosidase) is an enzyme activity you can detect at pH 6.0. It reflects the swollen lysosomes and extra β-galactosidase (made by the GLB1…

SAM (S-adenosylmethionine) is your body's main methyl-group donor. It is the molecule that hands out the chemical tags used to mark DNA, histones, neurotransmitters, and fats.…

The senescence-associated secretory phenotype (SASP) is the cocktail of molecules that senescent ('worn-out') cells pump out into the tissue around you. It includes cytokines,…

Senolytics are drugs that hunt down and kill senescent "zombie" cells, the worn-out cells that pile up in your tissues with age. They spare healthy cells. They work by exploiting…

Senomorphics are compounds that quiet senescent cells, rather than killing them. (They are also called senostatics.) Specifically, they tone down the harmful molecules these…

Sestrins (SESN1, SESN2, SESN3) are stress-triggered proteins, conserved across evolution. They turn down mTORC1 (a master growth switch) and turn up AMPK (an energy sensor), the…

The shelterin complex is a six-protein assembly. The six are TRF1, TRF2, TIN2, TPP1, POT1, and RAP1. It constantly coats the TTAGGG repeats at your chromosome ends. That stops…

Sirtuins are a family of seven enzymes (SIRT1 through SIRT7) that act as metabolic sensors. They strip chemical tags off other proteins (mainly acetyl groups) to tune metabolism,…

Stem cell exhaustion is the age-related decline of your tissue-resident stem cells. They drop in number, function, and regenerative power. Several things drive it. There is…

The stem cell niche is the local microenvironment that controls a stem cell. It is made of neighboring support cells, blood vessels, the extracellular matrix, soluble signals,…

Telomerase is an enzyme that rebuilds the caps on your chromosome ends. Technically, it is a ribonucleoprotein 'reverse transcriptase'. It pairs a protein part (TERT) with an RNA…

Telomeres are the protective caps on the ends of your chromosomes, a bit like the plastic tips on shoelaces. They are made of a short DNA sequence (TTAGGG) repeated over and…

Telomere attrition is the gradual shortening of the protective caps at your chromosome ends. (Those caps are repeats of the sequence TTAGGG.) They shorten a little with each cell…

TET1, TET2, and TET3 are enzymes that erase DNA methylation marks, step by step. (They are iron- and alpha-ketoglutarate-dependent dioxygenases.) They oxidize a methylated DNA…

TFEB (transcription factor EB) is a basic helix-loop-helix protein. It works as a master switch for autophagy and for building lysosomes (the cell's recycling centers that keep…

TGF-β (transforming growth factor β) signaling starts when TGF-β proteins (TGF-β1, β2, β3) bind a receptor complex (TβRII paired with TβRI). That complex tags messenger proteins…

The ubiquitin-proteasome system (UPS) is one of your cells' main ways to destroy proteins on purpose. It targets short-lived, misfolded, or regulatory proteins, and it…

The ULK1 complex is a four-part kinase assembly. It includes ULK1 (Unc-51-like autophagy-activating kinase 1), the scaffold FIP200, and two regulatory subunits, ATG13 and ATG101.…

The unfolded protein response (UPR) is a rescue program your cells run when misfolded proteins pile up in the endoplasmic reticulum (ER). Three sensors kick it off: IRE1alpha,…

Vascular calcification is the buildup of calcium-phosphate mineral (hydroxyapatite) in your artery walls. It is an active, cell-controlled process. It is not the passive…

Wnt signaling is a family of ancient cell-to-cell communication pathways. It starts when secreted Wnt proteins bind 'Frizzled' receptors on your cells. The most-studied branch is…

The Yamanaka factors are four transcription factors: OCT4, SOX2, KLF4, and c-MYC (together, OSKM). Shinya Yamanaka identified them in 2006. He showed they are enough to reprogram…