Biology of Aging

Adult stem cells, or somatic stem cells, are undifferentiated cells residing in specific tissue niches that maintain and repair the tissue throughout life. Examples include…

Advanced glycation end-products are stable, often crosslinked compounds formed when sugars react with proteins, lipids, or DNA over time. They accumulate in long-lived tissues…

The AGE-RAGE axis describes signalling initiated when advanced glycation end products (AGEs) and other endogenous ligands engage RAGE, a multiligand immunoglobulin-superfamily…

AMPK (AMP-activated protein kinase) is a cellular energy sensor activated when AMP and/or ADP relative to ATP rise, signaling low energy availability. Once active, it stimulates…

Angiogenesis is the formation of new blood vessels from pre-existing capillaries, driven by vascular endothelial growth factor-A (VEGF-A), a glycoprotein that binds receptor…

Apoptosis is a tightly regulated form of programmed cell death in which cells are dismantled in an orderly fashion via caspase activation, typically without triggering…

Atherosclerosis is a chronic, lipid-driven inflammatory disease of medium and large arteries in which ApoB-containing lipoproteins (primarily LDL) are retained within the…

Autophagy is a conserved lysosomal degradation pathway in which cells engulf damaged organelles, misfolded proteins, and other cytoplasmic material in double-membrane vesicles…

Beclin-1 (encoded by BECN1) is a core component of the class III phosphatidylinositol 3-kinase (PI3K-III / VPS34) complex that nucleates phagophore membranes at the initiation…

Biomolecular condensates are membraneless organelles formed through liquid-liquid phase separation (LLPS) — the spontaneous demixing of proteins and RNAs into a dense liquid…

Cardiolipin (CL) is a dimeric phospholipid found almost exclusively in the inner mitochondrial membrane (IMM), constituting roughly 15–20 % of total lipid content. Its four acyl…

Cathepsins are a family of lysosomal proteases — predominantly cysteine proteases (cathepsins B, C, H, K, L, S, V, X/Z) but also aspartyl (cathepsins D, E) and serine types…

CD38 is a transmembrane glycoprotein with NAD+ glycohydrolase and ADP-ribosyl cyclase activity, expressed broadly but most abundantly on immune cells. It hydrolyses NAD+ to…

Cellular reprogramming is the experimental conversion of one cell type into another, most often a differentiated somatic cell into a pluripotent stem cell, by forcing expression…

Cellular senescence is a stable cell-cycle arrest triggered by stressors such as DNA damage, telomere dysfunction, oncogene activation or oxidative stress. Senescent cells remain…

The cGAS-STING pathway is an innate immune sensing mechanism in which cyclic GMP-AMP synthase (cGAS) detects cytosolic double-stranded DNA — a signal of viral infection, nuclear…

Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation pathway in which individual cytosolic proteins carrying a KFERQ-like pentapeptide motif (a biochemical…

Chromatin is the complex of DNA, histones, and associated proteins that packages the genome inside the nucleus. Its basic unit, the nucleosome, can be tightly compacted as…

Cuproptosis is a copper-dependent form of regulated cell death that is mechanistically distinct from apoptosis, ferroptosis, necroptosis and pyroptosis. When intracellular copper…

DNA damage refers to chemical or structural alterations of the genome, including base modifications, single- and double-strand breaks, and crosslinks. It arises from reactive…

DNA methylation is an epigenetic modification in which methyl groups are added to cytosine bases, predominantly at CpG sites, by DNA methyltransferases. It regulates gene…

DNA methyltransferases (DNMTs) catalyse the transfer of a methyl group from S-adenosylmethionine to the 5-carbon of cytosine, primarily at CpG dinucleotides. In mammals, three…

Elastin is the extracellular matrix protein that confers recoil and elastic compliance to tissues under cyclical mechanical stress, particularly arterial walls, lungs, and skin;…

The electron transport chain (ETC) consists of four inner mitochondrial membrane protein complexes — Complex I (NADH:ubiquinone oxidoreductase), Complex II (succinate…

Endothelial dysfunction is a pathological state in which the inner lining of blood vessels — the endothelium — fails to maintain normal vascular homeostasis, most…

Epigenetic alterations are age-related changes in DNA methylation patterns, histone modifications, chromatin architecture and non-coding RNA expression that occur without changes…

Endoplasmic reticulum (ER) stress arises when the capacity of the ER to fold, modify, and quality-control secretory and membrane proteins is exceeded by the demand — triggered by…

The extracellular matrix (ECM) is the protein and proteoglycan scaffold that provides structural support and transmits biochemical and mechanical signals to resident cells; with…

Extracellular vesicles (EVs) are membrane-bound particles released by virtually all cell types and conventionally classified into exosomes (30–150 nm, endosomal origin via…

Ferroptosis is a form of regulated cell death driven by iron-dependent accumulation of lipid peroxides to lethal levels, distinguishing it mechanistically from apoptosis,…

FGF21 (fibroblast growth factor 21) is an endocrine member of the FGF superfamily secreted primarily by the liver in response to fasting, dietary protein restriction, and…

Fibrosis is the pathological excess deposition of extracellular matrix — predominantly fibrillar collagens type I and III — by activated myofibroblasts in response to chronic…

FOXO transcription factors (Forkhead box O) are downstream effectors of the insulin/IGF-1 pathway that regulate genes governing stress resistance, DNA repair, autophagy, and…

Free radicals are atoms or molecules carrying one or more unpaired electrons, which makes them highly reactive. They arise from normal metabolism, immune activity, and external…

GDF11 (growth differentiation factor 11) is a TGF-β superfamily ligand that plays an established role in axial patterning and organogenesis during embryonic development by…

GDF15 (growth differentiation factor 15), also known as MIC-1, is a divergent TGF-β superfamily member that is expressed at low levels under homeostatic conditions but is…

Genomic instability is the progressive accumulation of damage to nuclear and mitochondrial DNA, including point mutations, chromosomal rearrangements, copy-number changes and…

Glutathione (GSH) is the most abundant intracellular low-molecular-weight thiol, synthesised in two ATP-dependent steps from glutamate, cysteine, and glycine by…

Glycation is the non-enzymatic attachment of sugars such as glucose or fructose to proteins, lipids, or nucleic acids. Through the Maillard reaction it generates unstable Schiff…

The Hallmarks of Aging are a set of interconnected biological processes proposed by López-Otín and colleagues to describe the molecular and cellular drivers of ageing. The 2023…

The Hayflick limit is the maximum number of times a normal human somatic cell can divide in culture, typically 40 to 60 times, before entering replicative senescence. Discovered…

Heat shock proteins (HSPs) are a family of highly conserved molecular chaperones, named for their induction by heat but active under many forms of stress. They assist protein…

Haematopoietic stem cells (HSCs) are rare, multipotent progenitors residing primarily in the bone marrow that sustain lifelong blood cell production through asymmetric…

Heterochromatin is the condensed, transcriptionally repressed fraction of chromatin marked by histone modifications such as H3K9me2/3 and H3K27me3, and maintained by factors…

HIF-1α (hypoxia-inducible factor 1α) is the oxygen-regulated subunit of the HIF-1 heterodimeric transcription factor that drives the cellular and systemic transcriptional…

The Hippo pathway is a conserved kinase cascade — centred on MST1/2 and LATS1/2 kinases — that controls organ size, tissue homeostasis, and stem cell activity by phosphorylating…

Histone modifications are reversible chemical changes to histone proteins around which DNA is wound, including acetylation, methylation, phosphorylation, and ubiquitination. They…

Hormesis is a biphasic dose-response phenomenon in which a low or moderate dose of a stressor produces a beneficial adaptive effect, while higher doses are harmful. Mild…

IGF-1 signaling refers to the cascade triggered when insulin-like growth factor 1 binds the IGF-1 receptor, activating parallel PI3K/AKT and MAPK/ERK branches that promote cell…

Inflammaging describes the chronic, low-grade, sterile inflammation that develops with age in the absence of overt infection. It is characterised by often elevated baseline…

The insulin/IGF-1 pathway (often abbreviated IIS) is a conserved nutrient-sensing network in which insulin and IGF-1 bind tyrosine kinase receptors to activate PI3K, AKT, and…

The integrated stress response (ISR) is a conserved eukaryotic signalling programme that converges on phosphorylation of the alpha subunit of eukaryotic initiation factor 2…

Induced pluripotent stem cells (iPSCs) are adult somatic cells reprogrammed into a pluripotent state using factors such as OSKM (Oct4, Sox2, Klf4, c-Myc), capable of…

The JAK-STAT (Janus kinase – signal transducer and activator of transcription) pathway is a rapid, receptor-proximal signalling cascade through which cytokines and growth factors…

Klotho (here referring to alpha-Klotho, distinct from beta-Klotho) is a transmembrane protein, predominantly expressed in the kidney and brain, that also circulates as a soluble…

Lamin A is a type-V intermediate filament protein and major structural component of the nuclear lamina — the meshwork underlying the inner nuclear membrane — that is essential…

LC3 lipidation is the covalent conjugation of the autophagy protein LC3 (microtubule-associated protein 1 light chain 3) to phosphatidylethanolamine (PE) in the phagophore and…

Long interspersed nuclear elements-1 (LINE-1, or L1) are autonomous retrotransposons that comprise roughly 17% of the human genome; they encode the proteins ORF1p and ORF2p,…

Lipid peroxidation is an autocatalytic, radical-mediated oxidative degradation of polyunsaturated fatty acids (PUFAs) in cell membranes, lipoproteins, and lipid droplets,…

Lipofuscin is a yellow-brown, autofluorescent pigment composed of cross-linked oxidised proteins, peroxidised lipids, sugar adducts and redox-active metals such as iron. It forms…

Loss of proteostasis is one of the established hallmarks of aging and describes the age-related decline of the protein quality control network. Chaperones become less efficient,…

The lysosome is a membrane-bound organelle filled with acidic hydrolases that degrade proteins, lipids, nucleic acids, and carbohydrates delivered via endocytosis, phagocytosis,…

Methylglyoxal (MGO) is a highly reactive α-oxoaldehyde (dicarbonyl) formed as a spontaneous byproduct of glycolysis via non-enzymatic phosphate elimination from dihydroxyacetone…

Mitochondrial biogenesis is the process by which cells increase mitochondrial mass and capacity by coordinating the expression of nuclear and mitochondrial genes. The…

Mitochondrial DNA (mtDNA) is a circular, double-stranded genome of approximately 16,569 base pairs present in multiple copies per cell that encodes 13 essential subunits of the…

Mitochondrial dynamics refers to continuous cycles of fission (division) and fusion (merging) that remodel the mitochondrial network in response to metabolic demands and cellular…

Mitochondrial dysfunction refers to a decline in mitochondrial efficiency, including reduced ATP output, impaired electron transport chain activity, increased reactive oxygen…

The mitochondrial unfolded protein response (mtUPR) is a stress-signalling pathway activated when the capacity of mitochondrial chaperones — including HSP60, HSP70 and the AAA+…

Mitophagy is the selective form of autophagy that targets damaged or depolarized mitochondria for lysosomal degradation, with the PINK1/Parkin pathway being the…

mTOR (mechanistic target of rapamycin) is a serine/threonine kinase that integrates signals from amino acids, growth factors, and cellular energy status to regulate protein…

The mechanistic target of rapamycin (mTOR) kinase assembles into two structurally and functionally distinct multi-protein complexes: mTORC1, defined by its scaffold subunit…

Myostatin, also designated Growth Differentiation Factor 8 (GDF8), is a secreted member of the TGF-β superfamily and the principal negative regulator of skeletal muscle mass.…

NAD+ (nicotinamide adenine dinucleotide, oxidized form) is a coenzyme central to redox reactions in energy metabolism and a required substrate for sirtuins, PARPs, and CD38.…

NADH is the reduced form of NAD+, generated when NAD+ accepts electrons during glycolysis, the citric acid cycle, and fatty acid oxidation. It delivers electrons to the…

NAMPT (nicotinamide phosphoribosyltransferase) is the rate-limiting enzyme of the NAD+ salvage pathway — the primary route by which mammalian cells regenerate NAD+ from…

Necroptosis is a form of programmed necrotic cell death that proceeds through a defined molecular pathway involving receptor-interacting protein kinases RIPK1 and RIPK3 and the…

NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a family of transcription factors — comprising RelA, RelB, c-Rel, p50 and p52 subunits — that regulate…

Nitric oxide (NO) is a gaseous signaling molecule produced in vascular endothelium by endothelial NO synthase (eNOS, NOS3), converting L-arginine and O2 to NO and L-citrulline,…

The NLRP3 inflammasome is a multiprotein cytosolic complex — composed of the sensor protein NLRP3, the adaptor ASC and pro-caspase-1 — that assembles in response to a broad range…

While advanced glycation end-products (AGEs) are one well-known source of collagen crosslinks, a distinct class of enzyme-mediated crosslinks is introduced by lysyl oxidase (LOX)…

Notch signaling is a conserved juxtacrine pathway that governs cell-fate decisions, differentiation, and tissue homeostasis through direct cell-to-cell contact. Binding of…

NRF2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that orchestrates the cellular antioxidant and cytoprotective response by binding antioxidant…

Nuclear pore complex (NPC) aging refers to the progressive structural and functional deterioration of NPCs — the approximately 120 MDa protein channels that perforate the nuclear…

One-carbon metabolism is an interconnected network of folate and methionine cycles that transfers single-carbon units for the biosynthesis of nucleotides, the remethylation of…

Oxidative stress is an imbalance between reactive oxygen species production and the body's antioxidant defences, leading to oxidative damage of biomolecules. It impairs…

p16INK4a is a cyclin-dependent kinase inhibitor encoded by the CDKN2A locus that blocks CDK4/6, halting cell cycle progression and enforcing cellular senescence. Its expression…

p21, encoded by CDKN1A (cyclin-dependent kinase inhibitor 1A), is a potent inhibitor of cyclin-CDK complexes — particularly CDK2 — that enforces G1 and S phase cell-cycle arrest…

p38 MAPK (p38 mitogen-activated protein kinase), comprising four isoforms (α, β, γ, δ) with p38α being the predominant and most studied form, is a stress-activated kinase that is…

p53 is a tumour-suppressor protein encoded by the TP53 gene that acts as a central transcription factor in the cellular response to genotoxic stress, hypoxia, oncogene activation…

p62, encoded by the SQSTM1 gene, is a multifunctional scaffold and selective autophagy receptor that recognises ubiquitinated cargo through its UBA domain and delivers it to…

Parkin, encoded by the PRKN gene (formerly PARK2), is a RING-between-RING E3 ubiquitin ligase that operates at the centre of mitochondrial quality control. In the cytosol it is…

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

Partial reprogramming uses transient or low-dose expression of Yamanaka factors to rejuvenate cells without erasing their differentiated identity or inducing pluripotency.…

PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is a transcriptional co-activator and master regulator of mitochondrial biogenesis and oxidative…

The PI3K/AKT pathway is a central intracellular signalling axis activated by receptor tyrosine kinases (including the insulin and IGF-1 receptors), G-protein-coupled receptors,…

PINK1 (PTEN-induced kinase 1) is a mitochondrial serine/threonine kinase that serves as a sensor of mitochondrial damage. In healthy mitochondria with an intact membrane…

Protein carbonylation is an irreversible, oxidative post-translational modification in which carbonyl groups (aldehydes or ketones) are introduced into protein side chains, most…

Protein crosslinks are covalent bonds that join two protein molecules or different segments of the same protein. They can form enzymatically, as with collagen maturation, or…

Proteostasis, short for protein homeostasis, is the integrated network that controls protein synthesis, folding, trafficking, and degradation to keep the proteome functional. Key…

Pyroptosis is a highly inflammatory form of programmed cell death executed primarily by gasdermin family proteins, especially gasdermin D (GSDMD), which oligomerise to form pores…

Reactive oxygen species are oxygen-containing molecules such as superoxide, hydrogen peroxide, and hydroxyl radicals produced by multiple cellular sources, including…

Regenerative medicine is the field developing therapies to repair, replace, or regenerate damaged cells, tissues, and organs. Approaches include stem cell transplantation, tissue…

S6K1 (ribosomal protein S6 kinase 1, encoded by RPS6KB1) is a serine/threonine kinase and a primary downstream effector of mTORC1 that promotes protein synthesis by…

Senescence-associated β-galactosidase (SA-β-Gal) is an enzyme activity detectable at pH 6.0 that reflects the increased lysosomal content and elevated expression of lysosomal…

S-adenosylmethionine (SAM) is the principal biological methyl-group donor, formed by the condensation of methionine with adenosine triphosphate (ATP) in a reaction catalysed by…

The senescence-associated secretory phenotype, or SASP, is the complex mixture of cytokines, chemokines, growth factors, proteases and extracellular vesicles released by…

Senolytics are compounds that selectively induce cell death in senescent cells by exploiting context-specific survival vulnerabilities, including BCL-2 family proteins and…

Senomorphics, also called senostatics, are compounds that suppress the harmful secretory activity of senescent cells without killing them. They typically target signalling…

Sestrins (SESN1, SESN2, SESN3) are evolutionarily conserved, stress-inducible proteins that suppress mTORC1 (mechanistic target of rapamycin complex 1) and activate AMPK…

The shelterin complex is a six-protein assembly — TRF1, TRF2, TIN2, TPP1, POT1, and RAP1 — that constitutively coats the TTAGGG repeats at chromosome ends, preventing their…

Sirtuins are a family of seven NAD+-dependent enzymes (SIRT1–SIRT7) that deacetylate or otherwise modify proteins involved in metabolism, DNA repair, mitochondrial function, and…

Stem cell exhaustion is the age-related decline in the number, function, and regenerative capacity of tissue-resident stem cells. Drivers include accumulated DNA damage, telomere…

The stem cell niche is the spatially defined microenvironment — composed of neighbouring stromal cells, vascular elements, extracellular matrix, soluble factors, and biophysical…

Telomerase is a ribonucleoprotein reverse transcriptase (TERT plus the TERC RNA template) that adds TTAGGG repeats to chromosome ends, counteracting replicative shortening. It is…

Telomeres are repetitive TTAGGG DNA sequences capping the ends of linear chromosomes, protecting them from degradation, fusion, and erroneous repair. Each somatic cell division…

Telomere attrition is the progressive shortening of the protective TTAGGG repeat sequences at chromosome ends with each cell division, due to the end-replication problem and…

TET1, TET2 and TET3 are Fe(II)- and alpha-ketoglutarate-dependent dioxygenases that catalyse stepwise oxidation of 5-methylcytosine (5mC) on DNA to 5-hydroxymethylcytosine…

TFEB is a basic helix-loop-helix transcription factor that acts as a master regulator of autophagy and lysosomal biogenesis. It binds a conserved promoter motif called the CLEAR…

Transforming growth factor β (TGF-β) signaling is initiated when TGF-β ligands — including TGF-β1, TGF-β2, and TGF-β3 — bind to heteromeric serine/threonine kinase receptor…

The ubiquitin-proteasome system (UPS) is a major route for selective degradation of short-lived, misfolded, or regulatory proteins, complementary to autophagy-lysosomal…

The ULK1 complex is a tetrameric serine/threonine kinase assembly comprising ULK1 (Unc-51-like autophagy-activating kinase 1), scaffold FIP200, and regulatory subunits ATG13 and…

The unfolded protein response (UPR) is an adaptive signalling programme activated when misfolded or unfolded proteins accumulate in the endoplasmic reticulum (ER), engaging three…

Vascular calcification is an active, cell-regulated process in which hydroxyapatite deposits within the arterial wall, not a passive precipitation as once assumed. Two…

Wnt signaling is a family of evolutionarily conserved intercellular communication pathways initiated by secreted Wnt glycolipoproteins binding to Frizzled receptors, with the…

The Yamanaka factors are four transcription factors, OCT4, SOX2, KLF4, and c-MYC (OSKM), identified by Shinya Yamanaka in 2006 as sufficient to reprogram differentiated somatic…