Pathways

AMPK (AMP-Activated Protein Kinase)

The cell's energy sensor — activated when ATP drops — that switches metabolism from anabolic growth to catabolic repair.

Autophagy Machinery

The conserved set of ATG proteins that assemble the autophagosome — the central recycling system whose decline is a hallmark of aging.

cGAS-STING Pathway

The innate-immune sensor for cytosolic DNA. Chronic activation by leaked mitochondrial DNA and senescent-cell debris is now considered a central driver of inflammaging.

FOXO Transcription Factors

A family of stress-response transcription factors downstream of insulin/IGF-1 whose activation drives a longevity-protective gene programme.

HSF1 / Heat-Shock Response

The conserved transcriptional program that produces chaperones in response to proteotoxic stress. HSF1 activity declines with age, contributing to proteostatic collapse.

Insulin / IGF-1 Signalling

The conserved growth-promoting axis whose attenuation extends lifespan across species. Lower IGF-1 in midlife associates with longer human lifespan.

Integrated Stress Response (ISR)

A convergent translational-control pathway that pauses protein synthesis under diverse stresses. Chronic activation underlies memory deficits and is a tractable drug target.

Klotho

A circulating anti-aging hormone (and membrane receptor) whose loss in mice produces a striking premature-aging phenotype and whose gain extends lifespan.

Lysosomal Function

The cellular recycling organelle whose acidification, enzyme content, and signalling role (via mTORC1) all decline with age. Lysosomal dysfunction underlies most lysosomal storage diseases and neurodegeneration.

Mitochondrial Unfolded Protein Response (mtUPR)

Stress-response pathway that detects misfolded proteins inside mitochondria and signals to the nucleus for adaptive transcription. Activation extends lifespan in worms and likely in mammals.

Mitophagy (PINK1 / Parkin)

Selective autophagy of damaged mitochondria. Failure of mitophagy accumulates dysfunctional mitochondria and drives mitochondrial-dysfunction hallmarks.

mTOR (Mechanistic Target of Rapamycin)

Conserved nutrient-sensing kinase that decides whether cells grow or repair. Chronic activation accelerates aging; inhibition extends lifespan in every species tested.

NF-κB

The master pro-inflammatory transcription factor whose chronic activation underpins inflammaging and most age-related diseases.

NLRP3 Inflammasome

The cytosolic multi-protein platform that activates caspase-1 and matures IL-1β. Chronic activation drives gout, atherosclerosis, type-2 diabetes, and many age-related inflammatory conditions.

PGC-1α (Mitochondrial Biogenesis)

The master transcriptional co-activator that drives mitochondrial biogenesis, oxidative metabolism, and exercise adaptation.

PI3K / AKT Signalling

The growth and survival pathway that connects insulin/IGF-1 receptors to mTOR, FOXO, and glucose handling. Dysregulation drives cancer, metabolic disease, and accelerated aging.

Polyamine Metabolism

Putrescine, spermidine, and spermine are essential polycations whose levels decline with age. Restoring spermidine extends lifespan in many species and may protect cardiovascular and cognitive function in humans.

Sirtuins (SIRT1–SIRT7)

A family of NAD+-dependent deacylase enzymes linking nutrient state to chromatin, mitochondria, and metabolism.

Telomerase (TERT / TERC)

The reverse-transcriptase enzyme that extends telomeres. Silenced in most adult somatic cells, active in stem and cancer cells — a double-edged longevity target.

TGF-β Signalling

Master regulator of fibrosis, immune tolerance, and tissue homeostasis. TGF-β tone rises with age and is implicated in stem-cell decline, fibrosis, and many age-related diseases.

Wnt Signalling

Conserved developmental pathway that regulates stem-cell maintenance, tissue repair, and bone biology. Aberrant activity drives cancer; declining activity contributes to stem-cell exhaustion.