access company
approved, unapproved
app company
autophagy
autophagy (disabled macroautophagy)
autophagy-dependent stem-cell quiescence
Mitochondrial clearance; metabolic restraint; hematopoietic self-renewalDisabled macroautophagy; stem cell exhaustion; mitochondrial dysfunction (editorial mapping)
Autophagy can preserve a low metabolic state in hematopoietic stem cells by clearing active mitochondria. In mice, core autophagy-gene loss impaired regeneration, while roughly one-third of old stem cells retained high autophagy and strong transplantation-based function. The study did not test a drug that converts low-autophagy cells into this state. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/28241143/
big industrial R&D
broad platform
cell communication
altered intercellular communication
blood factors & parabiosis work goes here
clocks
includes epigenetic clocks, but also other types
cytosolic DNA sensing
cGAS–STING; mitochondrial DNA release; innate immune activationMitochondrial dysfunction; chronic inflammation (editorial mapping)
Mechanism category for inflammatory responses to misplaced DNA, including mitochondrial DNA in aged microglia. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/37532932/
ECM
extracellular crosslinks / matrix stiffeningaltered mechanical properties
AGE crosslinks go here
ECM mechanotransduction
Matrix mechanics; collagen turnover; tissue-force signalingAltered intercellular communication (editorial mapping)
Editorial subcategory within extracellular-matrix biology. Separates force-dependent signaling and remodeling from chemical AGE-crosslink cleavage; the cited causal aging evidence is in nematodes. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/38177158/
endosomal microautophagy
hsc70 cargo selection; ESCRT-dependent late-endosomal uptakeLoss of proteostasis (editorial mapping)
Selective delivery of soluble cytosolic proteins into late endosomes, distinct from macroautophagy and lysosomal chaperone-mediated autophagy. The founding cell and organelle experiments established the pathway rather than an aging intervention. Sources verified 2026-09-28: https://pmc.ncbi.nlm.nih.gov/articles/PMC3025279/
epigenetic
epigenetic alterationsepigenetics
aka 'reprogramming'
extracellular vesicles
Cell-derived signals and regenerative cargoaltered intercellular communication
Editorial subcategory for vesicle-mediated signaling and experimental regenerative approaches. The cited young-cell vesicle study concerns mice, not established clinical rejuvenation. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/36260670/
genomic
nuclear mutations / cancergenomic instabilitymacromolecular damage
retrotransposons goes here, but should they be moved to splicing?
immune rejuvenation
Hematopoietic stem-cell composition and immune functionstem cell exhaustion; altered intercellular communication
Editorial grouping for interventions targeting age-related immune dysfunction. The cited antibody-based stem-cell intervention was tested in mice. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/38538791/
inflammation
(chronic) inflammationinflammation
intracell junk
intracellular junk
lipofuscin clearance goes here
klotho
local IGF1 signaling in the marrow niche
Bone-marrow growth factors; hematopoietic lineage bias; mitochondrial activityAltered intercellular communication; stem cell exhaustion (editorial mapping)
Declining local marrow IGF1 contributed to middle-aged mouse hematopoietic stem-cell dysfunction. Ex-vivo IGF1 exposure improved molecular features and lineage output after transplantation. This tissue-specific result illustrates why reduced systemic growth signaling and preserved local stem-cell support can have different effects; it does not establish systemic IGF1 treatment for aging. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/33848471/
lysosomal function
Chaperone-mediated autophagy and protein clearanceloss of proteostasis
Editorial subcategory for lysosomal degradation and accumulated intracellular material. Chaperone-mediated autophagy is mechanistically distinct from macroautophagy. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/18690243/
metabolism
mTORderegulated nutrient sensingmetabolism
microbiome
microbiome disturbance / disbiosis
where should non-GI junction gaps go, eg BBB disruption?
mitochondria
NAD+mitochondrial mutationsmitochondrial dysfunction
mitochondria-derived vesicle clearance
mitochondrial cargo sorting; oxidative-stress response; lysosomal deliveryMitochondrial dysfunction; loss of proteostasis (editorial mapping)
Vesicles carry selected mitochondrial cargo to lysosomes through a route that can operate without whole-organelle mitophagy. Initial evidence came from cultured-cell trafficking experiments, not organismal lifespan studies. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/22226745/
mitochondrial unfolded-protein response
Mitonuclear protein balance; mitochondrial stress signalingMitochondrial dysfunction; loss of proteostasis (editorial mapping)
Editorial subcategory for adaptive mitochondrial protein-quality signaling, distinct from selective mitochondrial removal. Pathway activation alone is not proof of human longevity benefit. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/23698443/
mitophagy
Selective mitochondrial quality controlmitochondrial dysfunction; disabled macroautophagy
Editorial subcategory connecting mitochondria and autophagy. Includes selective removal of damaged mitochondria; distinct from a claim that every mitophagy inducer extends human lifespan. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/27400265/
NLRP3 inflammasome signaling
NLRP3-ASC-caspase-1 activation; sterile inflammation; IL-1 signalingChronic inflammation; altered intercellular communication (editorial mapping)
Innate immune sensing pathway linked to age-associated sterile inflammation. Lifelong Nlrp3 deletion reduced inflammatory and degenerative phenotypes in aged mice, with IL-1-dependent contributions to cognitive and motor outcomes. The experiment did not test a drug started late in life. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/24093676/
Overall notes:
The primary goal here is to be able to group together similar efforts within the aging/longevity focused subset of the biotech field, which is a different goal than any of the other 3 frameworks started with.
pet longevity
Companion-animal geroscience
Cross-cutting application category rather than a formal hallmark. Includes longitudinal aging studies, veterinary interventions, and age-related diagnostics in companion animals. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/35110758/
physiological resilience and robustness
Resistance to damage; recovery; longitudinal deficit transitions
Editorial cross-cutting category, not an additional formal hallmark. Covers the distinction between resisting health deficits and recovering from them, using repeated functional measurements. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/36409200/
proteostasis
extracellular junkloss of proteostasisproteostasis
retrotransposon control
LINE-1 repression; reverse transcription; innate immune activationGenomic instability; chronic inflammation (editorial mapping)
Editorial mechanism category connecting repetitive-element activity and inflammatory signaling. The cited intervention evidence is in senescent cells and aged mice. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/30728521/
senescence
cell senescencecellular senescence
splicing
splicing dysregulation
stem cells
allogeneic, autologous, secretionscell loss & atrophystem cell exhaustionstem cell regeration
stem-cell polarity
Cdc42 activity; asymmetric cellular organization; H4K16 acetylationStem cell exhaustion; epigenetic alterations (editorial mapping)
Spatial organization of cellular components and chromatin marks can affect stem-cell function. In aged mouse hematopoietic stem cells, reducing excess Cdc42 activity restored polarity and improved transplantation-based function. Evidence for this category does not imply that systemic Cdc42 inhibition is a validated therapy. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/22560076/
stress
stress
hormesis goes here
telomeres
telomere attrition
transcriptional fidelity and elongation
RNA polymerase II speed; nucleosome maintenance; cotranscriptional RNA processingEpigenetic alterations (editorial mapping)
Mechanism category for age-related changes in transcription kinetics and RNA processing, including experimental manipulation of polymerase speed. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/37046086/
umbrella company
| Select up to four records | |||||
|---|---|---|---|---|---|
| access company | approved, unapproved | — | — | — | |
| app company | — | — | — | — | |
| autophagy | — | — | autophagy (disabled macroautophagy) | — | |
| autophagy-dependent stem-cell quiescence Autophagy can preserve a low metabolic state in hematopoietic stem cells by clearing active mitochondria. In mice, core autophagy-gene loss impaired regeneration, while roughly one-third of old stem cells retained high autophagy and strong transplantation-based function. The study did not test a drug that converts low-autophagy cells into this state. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/28241143/ | Mitochondrial clearance; metabolic restraint; hematopoietic self-renewal | — | Disabled macroautophagy; stem cell exhaustion; mitochondrial dysfunction (editorial mapping) | — | |
| big industrial R&D | — | — | — | — | |
| broad platform | — | — | — | — | |
| cell communication blood factors & parabiosis work goes here | — | — | altered intercellular communication | — | |
| clocks includes epigenetic clocks, but also other types | — | — | — | — | |
| cytosolic DNA sensing Mechanism category for inflammatory responses to misplaced DNA, including mitochondrial DNA in aged microglia. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/37532932/ | cGAS–STING; mitochondrial DNA release; innate immune activation | — | Mitochondrial dysfunction; chronic inflammation (editorial mapping) | — | |
| ECM AGE crosslinks go here | — | extracellular crosslinks / matrix stiffening | altered mechanical properties | — | |
| ECM mechanotransduction Editorial subcategory within extracellular-matrix biology. Separates force-dependent signaling and remodeling from chemical AGE-crosslink cleavage; the cited causal aging evidence is in nematodes. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/38177158/ | Matrix mechanics; collagen turnover; tissue-force signaling | — | Altered intercellular communication (editorial mapping) | — | |
| endosomal microautophagy Selective delivery of soluble cytosolic proteins into late endosomes, distinct from macroautophagy and lysosomal chaperone-mediated autophagy. The founding cell and organelle experiments established the pathway rather than an aging intervention. Sources verified 2026-09-28: https://pmc.ncbi.nlm.nih.gov/articles/PMC3025279/ | hsc70 cargo selection; ESCRT-dependent late-endosomal uptake | — | Loss of proteostasis (editorial mapping) | — | |
| epigenetic aka 'reprogramming' | — | — | epigenetic alterations | epigenetics | |
| extracellular vesicles Editorial subcategory for vesicle-mediated signaling and experimental regenerative approaches. The cited young-cell vesicle study concerns mice, not established clinical rejuvenation. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/36260670/ | Cell-derived signals and regenerative cargo | — | altered intercellular communication | — | |
| genomic retrotransposons goes here, but should they be moved to splicing? | — | nuclear mutations / cancer | genomic instability | macromolecular damage | |
| immune rejuvenation Editorial grouping for interventions targeting age-related immune dysfunction. The cited antibody-based stem-cell intervention was tested in mice. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/38538791/ | Hematopoietic stem-cell composition and immune function | — | stem cell exhaustion; altered intercellular communication | — | |
| inflammation | — | — | (chronic) inflammation | inflammation | |
| intracell junk lipofuscin clearance goes here | — | intracellular junk | — | — | |
| klotho | — | — | — | — | |
| local IGF1 signaling in the marrow niche Declining local marrow IGF1 contributed to middle-aged mouse hematopoietic stem-cell dysfunction. Ex-vivo IGF1 exposure improved molecular features and lineage output after transplantation. This tissue-specific result illustrates why reduced systemic growth signaling and preserved local stem-cell support can have different effects; it does not establish systemic IGF1 treatment for aging. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/33848471/ | Bone-marrow growth factors; hematopoietic lineage bias; mitochondrial activity | — | Altered intercellular communication; stem cell exhaustion (editorial mapping) | — | |
| lysosomal function Editorial subcategory for lysosomal degradation and accumulated intracellular material. Chaperone-mediated autophagy is mechanistically distinct from macroautophagy. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/18690243/ | Chaperone-mediated autophagy and protein clearance | — | loss of proteostasis | — | |
| metabolism | mTOR | — | deregulated nutrient sensing | metabolism | |
| microbiome where should non-GI junction gaps go, eg BBB disruption? | — | — | microbiome disturbance / disbiosis | — | |
| mitochondria | NAD+ | mitochondrial mutations | mitochondrial dysfunction | — | |
| mitochondria-derived vesicle clearance Vesicles carry selected mitochondrial cargo to lysosomes through a route that can operate without whole-organelle mitophagy. Initial evidence came from cultured-cell trafficking experiments, not organismal lifespan studies. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/22226745/ | mitochondrial cargo sorting; oxidative-stress response; lysosomal delivery | — | Mitochondrial dysfunction; loss of proteostasis (editorial mapping) | — | |
| mitochondrial unfolded-protein response Editorial subcategory for adaptive mitochondrial protein-quality signaling, distinct from selective mitochondrial removal. Pathway activation alone is not proof of human longevity benefit. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/23698443/ | Mitonuclear protein balance; mitochondrial stress signaling | — | Mitochondrial dysfunction; loss of proteostasis (editorial mapping) | — | |
| mitophagy Editorial subcategory connecting mitochondria and autophagy. Includes selective removal of damaged mitochondria; distinct from a claim that every mitophagy inducer extends human lifespan. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/27400265/ | Selective mitochondrial quality control | — | mitochondrial dysfunction; disabled macroautophagy | — | |
| NLRP3 inflammasome signaling Innate immune sensing pathway linked to age-associated sterile inflammation. Lifelong Nlrp3 deletion reduced inflammatory and degenerative phenotypes in aged mice, with IL-1-dependent contributions to cognitive and motor outcomes. The experiment did not test a drug started late in life. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/24093676/ | NLRP3-ASC-caspase-1 activation; sterile inflammation; IL-1 signaling | — | Chronic inflammation; altered intercellular communication (editorial mapping) | — | |
| Overall notes: | The primary goal here is to be able to group together similar efforts within the aging/longevity focused subset of the biotech field, which is a different goal than any of the other 3 frameworks started with. | — | — | — | |
| pet longevity Cross-cutting application category rather than a formal hallmark. Includes longitudinal aging studies, veterinary interventions, and age-related diagnostics in companion animals. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/35110758/ | Companion-animal geroscience | — | — | — | |
| physiological resilience and robustness Editorial cross-cutting category, not an additional formal hallmark. Covers the distinction between resisting health deficits and recovering from them, using repeated functional measurements. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/36409200/ | Resistance to damage; recovery; longitudinal deficit transitions | — | — | — | |
| proteostasis | — | extracellular junk | loss of proteostasis | proteostasis | |
| retrotransposon control Editorial mechanism category connecting repetitive-element activity and inflammatory signaling. The cited intervention evidence is in senescent cells and aged mice. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/30728521/ | LINE-1 repression; reverse transcription; innate immune activation | — | Genomic instability; chronic inflammation (editorial mapping) | — | |
| senescence | — | cell senescence | cellular senescence | — | |
| splicing | — | — | splicing dysregulation | — | |
| stem cells | allogeneic, autologous, secretions | cell loss & atrophy | stem cell exhaustion | stem cell regeration | |
| stem-cell polarity Spatial organization of cellular components and chromatin marks can affect stem-cell function. In aged mouse hematopoietic stem cells, reducing excess Cdc42 activity restored polarity and improved transplantation-based function. Evidence for this category does not imply that systemic Cdc42 inhibition is a validated therapy. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/22560076/ | Cdc42 activity; asymmetric cellular organization; H4K16 acetylation | — | Stem cell exhaustion; epigenetic alterations (editorial mapping) | — | |
| stress hormesis goes here | — | — | — | stress | |
| telomeres | — | — | telomere attrition | — | |
| transcriptional fidelity and elongation Mechanism category for age-related changes in transcription kinetics and RNA processing, including experimental manipulation of polymerase speed. Sources verified 2026-09-28: https://pubmed.ncbi.nlm.nih.gov/37046086/ | RNA polymerase II speed; nucleosome maintenance; cotranscriptional RNA processing | — | Epigenetic alterations (editorial mapping) | — | |
| umbrella company | — | — | — | — |