@prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> .
@prefix owl: <http://www.w3.org/2002/07/owl#> .
@prefix dc: <http://purl.org/dc/elements/1.1/> .
@prefix obo: <http://purl.obolibrary.org/obo/> .
@prefix pmid: <http://denigma.org/resource/PubMed/> .
@prefix : <http://denigma.org/resource/> .
# Definition of Aging
:Aging rdfs:subClassOf :Developmental_Process ;
:decreases :Homeostasis ;
:is_part_of :Organismal_Life ;
:includes :Disease_Resistance_Loss, :Homeostasis_Loss, :Fertility_Loss, :Wear_and_Tear ;
:may_precede :Death ;
:may_succeed :Developmental_Maturation ;
:is_characterized_by :Fitness_Loss ;
:is :Youthfulness_Loss ;
:increases_likelihood_of :Chronic_Disease ;
:causes :Muscle_Loss ;
:affords_the_onset_of :Disease ;
:encompases_all_the :Late_Life_Dysfunction ;
:has_significant_impact_on :Society ;
:is_the_major_cause_of :Mortality ;
:is_related_to :Organismal_Change ;
:leads_to :Adaptability_Loss ; # leading to
:results_in_having_an_increased :Age ;
:is_among_the :Largest_Known_Risk_Factor ;
:for :Human_Disease ;
:object :most ;
:is_the (:Major_Cause :of :Mortality) ;
:in_the :Developed_World ;
:affects :Inanimate_Object, :Living_Creature ;
rdfs:label "Aging" ;
:de_label "Alterung" ;
:de_definition "Jede gesetzmäßige Veränderung der lebenden Substanz als Function der Zeit" ;
:synonym "Ageing", "Senescence", "Aging Process", "Ageing Process", "Degenerative Aging Process", "Degenerative Ageing Process" ;
:definition "The time-dependent progressive functional decline, or a gradual deterioration of physiological function with age that affects most living organism; the program which limits lifespan in most organisms." ;
:definition "A measurable set of biological processes leading to an increasing risk of frailty, diseases and death with age" ;
:definition """The progressive, lifelong accumulation of changes to a living organism's molecular and cellular structure and composition ("damage"), occuring as intrinsic side-effects of the body's normal metabolism, which eventually overwhlem the body's homeostatic machinery and drive progressive decline in physiological function, leading ultimately to death.""" ;
:definition "A gradual but relentless process by which sexually-reproducing organisms lose their youthful capacity for homeostasis" ;
:description """Aging is the gradual decline in organismal homeostasis and of physiological functions throughout the body, and is associated with an increased risk of age-related disease.
Aging is the consequence of development and the cause of age-related disease. In molecular terms it is the decline of homeostatic mechanisms that ensure the function of cells, tissue, organs and organs systems. Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to health. Aging is part of the life of an organism. **Every** instance of aging is part of life of some organism. However not **every** instance of life of organism has as part aging, because a life may be cut short by early death or the organism is biological immortal.
Aging is a physical process that does not normally reveal itself until after the completion of a species-specific interval of reproductive competence during which adults read their progeny from childhood to independence. As a result of aging, older organisms become increasingly vulnerable to a variety of age-related disease and condition, culminating in death. The tradeoff between aging and repair processes is extremely complex and observed to operate systematically within a hierarchy of at least seven different interacting levels:
4. Tissues with various histologial architectures;
6. Organ systems; and ultimately
7. The entire organism itself.
Aging is not normally often obviously observed in wild populations, but typically manifests itself in zoos, as virtually all post-reproductive feral creatures are removed from the population by predators once they lose their agility. Aging is a physcal process that affects inanimate objects as well as living creatures (in the same way that the Egyptian pyramids are subject to wind and rain erosion.
Aging is the gradually progressing - and so far inevitable - decline of physiological functions eventually leading to death.
Aging is the major risk factor for cardiovascular morbidity and mortality [Lakatta, Heart Failure Rev. 2002].
owl:equivalentClass obo:GO_0007568, <http://dbpedia.org/resource/Ageing> ;
rdfs:seeAlso <http://en.wikipedia.org/wiki/Ageing> ;
rdfs:seeAlso <http://denigma.de/links/category/aging/> ;
rdfs:seeAlso <https://www.youtube.com/watch?v=JRqPJdgdnIM> ;
rdfs:seeAlso <http://linkedlifedata.com/resource/umls-concept/C0001811> ;
rdfs:seeAlso <http://www.crystalinks.com/aging.html> .
:Intrinsic_Aging rdfs:subClassOf :Aging ;
:is :intrinsic ;
:occurs_silently_from_within_starting_at_the :Molecular_Level ;
:synonym "Senescence" ;
:description "Intrinsic aging is an increase in vulnerability to age-related diseases leading to the death of an individual secondary to a natural process related to the second law of thermodynamics (entropy). Intrinsic aging or senescence occurs silently from within starting at the molecular level, in the same sense that termites, if unchecked, will sooner or later, destroy the structural intigrity of even the largest wooden house." .
:Extrinsic_Aging rdfs:subClassOf :Aging ;
:is :extrinsic ;
:description "Extrinsic aging corresponds to external trauma or predation, in the same sense that a lightening bold from above can start a fire that burns your house down" .
:Agility rdfs:subClassOf :Gracefulness ;
:synonym "Legerity", "Lightness", "Lightsomeness", "Nimbleness" ;
:definition "The gracefulness of a person or animal that is quick ad nimble" .
:definition "Small membrane-bound cellular components with spezialized functions" .
:Histological_Architecture rdfs:subClassOf :Architecture ;
:is :histological .
:Gradual_Process rdfs:subClassOf :Process ;
:is :gradual .
:Relentless_Process rdfs:subClassOf :Process ;
:is :relentless .
:Physical_Process rdfs:subClassOf :Process ;
:is :physical ;
:synonym "Process" ;
:definition "A sustained phenomenon or one marked by gradual changes through a series of states" .
:aging a :Object_Modifier ;
:synonym "ageing", "senescent" ;
:definition "Growing old; elderly", "reaching the end of useful life; obsolescent" .
:Wear_and_Tear rdfs:subClassOf :Damage ;
rdfs:seeAlso <http://en.wikipedia.org/wiki/Wear_and_tear> .
:Rejuvenation rdfs:subClassOf :Restoration, :Organic_Phenomenon ;
:is_the (:Reversal :of :Aging) ;
:is_distinct_from :Life_Extension ;
:can_be (:Means :of :Life_Extension) ;
:definition "The act of restoring a more youthful condition; the phenomenon of vitality and freshness being restored" ;
:description "Rejuvenation is the reversal of aging." ;
rdfs:seeAlso <https://www.youtube.com/watch?v=OISoYZoyUuA&feature=youtu.be> .
:Life_Extension_Strategy rdfs:subClassOf :Strategy ;
:for :Life_Extension ;
:do_not_involve :Rejuvenation ;
:subject :most .
:Life_Expectancy_Increase rdfs:subClassOf :Increase ;
:is_due_to :Death_Rate_Decrease .
:Aging_Rate rdfs:subClassOf :Rate ;
:synonym "Ageing Rate", "Rate of Aging", "Rate of Ageing" .
:Aging_Sign rdfs:subClassOf :Sign ;
:synonym "Sign of Aging" .
# Types of Aging
:Biological_Aging rdfs:subClassOf :Aging ;
:definition "An organism's physical state as it ages" .
:Non-Biological_Aging rdfs:subClassOf :Aging ;
:synonym "Non-Biotic Aging" ;
owl:disjointWith :Biological_Aging .
:Organismal_Aging rdfs:subClassOf :Aging ;
:of :Organism .
:Organ_Aging rdfs:subClassOf :Aging ;
:of :Organ .
:Tissue_Aging rdfs:subClassOf :Aging ;
:of :Tissue .
:Cell_Aging rdfs:subClassOf :Aging ;
:of :Cell ;
owl:equivalentClass obo:GO_0007569 ;
:synonym "Cellular Aging" .
:Chronological_Aging rdfs:subClassOf :Cell_Aging ;
:is :reversible ;
:definition "The mere passing of time during the existence of an entity" .
:Replicative_Aging rdfs:subClassOf :Cell_Aging ;
:is :reversible .
:Molecular_Aging rdfs:subClassOf :Aging .
:Skin_Aging rdfs:subClassOf :Tissue_Aging ;
:converges_on :Dermal_Stroma .
:Stem_Cell_Aging rdfs:subClassOf :Aging ;
:of :Stem_Cell .
:Mammalian_Aging rdfs:subClassOf :Organismal_Aging .
:Human_Aging rdfs:subClassOf :Organismal_Aging ; #(Aging and hasParticipant some Human);
:of :Homo_sapiens .
[ a owl:Restriction ;
:hasProperty :participant_of_some ;
:hasSomeValue :Human_Aging ;
:Developmental_Aging rdfs:subClassOf :Aging ;
:is_a_special_kind_of :Aging .
:Delayed_Aging rdfs:subClassOf :Aging ;
:synonym "Retarded Aging" .
:Normal_Aging rdfs:subClassOf :Aging ;
:synonym "Normal-Rate Aging" .
:Abnormal_Aging rdfs:subClassOf :Aging ;
owl:disjointWith :Normal_Aging .
:Universal_Aging rdfs:subClassOf :Aging ;
:definition "Age changes that all aging organisms share" .
:Probabilistic_Aging rdfs:subClassOf :Aging ;
:definition "Age changes that may happen to some, but not all aging organisms as they grow older including diseases such as type two diabetes" .
:Social_Aging rdfs:subClassOf :Aging ;
:definition "Cultural age-expectations of how people should act as they grow older" .
:Proximal_Aging rdfs:subClassOf :Aging ;
:definition "Age-based effects that come about because of factors in the recent past" .
:Distal_Aging rdfs:subClassOf :Aging ;
:definition "Age-based differences that can be traced back to a cause early in person's life, such as childhood poliomyelitis" .
:Population_Aging rdfs:subClassOf :Aging ;
:description "Population aging is the increase in the number and proportion of older people in society. Population aging has three possible causes: migration, longer life expectancy (decreased death rate), and decreased birth rate." ;
:is_caused_by :Migration, :Life_Expactancy_Increase, :Birth_Rate_Decrease .
# The Hallmarks of Aging
:Candidate_Hallmark rdfs:subClassOf :Hallmark .
:Canonical_Hallmark rdfs:subClassOf :Hallmark .
:Species-Specific_Hallmark rdfs:subClassOf :Hallmark .
:Tissue-Specific_Hallmark rdfs:subClassOf :Hallmark .
:Molecular_Hallmark rdfs:subClassOf :Hallmark .
:Cellular_Hallmark rdfs:subClassOf :Hallmark .
:Primary_Hallmark rdfs:subClass :Hallmark ;
:definition "Causes of damage" .
:Antagonist_Hallmark rdfs:subClassOf :Hallmark ;
:definition "Responses to damage" .
:Interative_Hallmark rdfs:subClassOf :Hallmark ;
:definition "Culprits of the phenotype" .
:Aging_Hallmark rdfs:subClassOf :Hallmark ;
:synonym "Hallmark of Aging" ;
:description """A hallmark of aging should ideally fulfill the following criteria:
1. It shold manifst during normal aging
2. Its experimental aggravation should accelerate aging
3. Its experimantal amelioration should retard the normal aging process and hence increase healthy lifespan
Experimental amelioration of one particular hallmark may impinge on others
:Genomic_Stability rdfs:subClassOf :Stability .
:Nuclear_Architecture rdfs:subClassOf :Architecture .
:Genomic_Instability rdfs:subClassOf :Aging_Hallmark, :Primary_Hallmark ;
owl:disjointWith :Genomic_Stability ;
:description "A common denominator of aging is the accumulation of genetic damage throughout life [Mosalec et al. 2012]. It includes DNA lesions. The inablity to repair/XS damage results in aging. There are various repair pathways for differen types of damages." .
:Mutation :part_of :Genomic_Instability .
:Telomere_Attrition rdfs:subClassOf :Aging_Hallmark, :Primary_Hallmark ;
:description "Normal aging is accompanied by telomere attrition in mammals. Pathological telomere dysfunction accelerates aging in mice and humans, whereas experimental stimulaiton of telomerase can delay aging in mice." .
:Epigenetic_Alteration rdfs:subClassOf :Aging_Hallmark, :Primary_Hallmark, :Alteration ;.
:Proteostasis_Loss rdfs:subClassOf :Aging_Hallmark, :Primary_Hallmark, :Loss ;
:synonym "Loss of Proteostasis" .
:Nutrient_Sensing_Deregulation rdfs:subClassOf :Deregulation, :Aging_Hallmark, :Antangonistic_Hallmark ;
:synonym "Deregulated_Nutrient_Sensing" .
:Mitochondrial_Dysfunction rdfs:subClassOf :Aging_Hallmark, :Antagonistic_Hallmark, :Dysfunction ;
:of_the :Mitochondrion .
:Cellular_Senescence rdfs:subClassOf :Senescence, :Aging_Hallmark, :Antagonistic_Hallmark .
:Stem_Cell_Exhaustion rdfs:subClassOf :Exhaustion, :Aging_Hallmark, :Integrative_Hallmark .
:Intracellular_Communication_Alteration rdfs:subClassOf :Alteration, :Aging_Hallmark, :Integrative_Hallmark ;
:synonym "Altered_Intercellular_Communication" .
:Integrity a owl:Class .
:Stability a owl:Class .
:Mitochondrial_DNA_Integrity rdfs:subClassOf :Integrity ;
:synonym "Integrity of Mitochondrial DNA" .
:Excessive_DNA_Damage rdfs:subClass :Excess ;
:favours :Aging .
:Insufficient_DNA-Repair rdfs:subClassOf :Insufficience ;
:favours :Aging .
:Laminopathy rdfs:subClassOf :Genetic_Disease ;
:description "Defects in the nuclear architecture (laminopthies) can cuase genome instability and result in premature aging syndromes [Woman, 2012]." ;
:definition "Defects in nuclear architecture." ;
:can_cause :Genomic_Instability ;
:can_results_in :Progeria .
:Age-Associated_Genomic_Alteration rdfs:subClassOf :Genomic_Alteration .
:Aging_Hallmark_Criterion a :Criterion ;
* Manifests during normal aging
* Experimental aggravation accelerates aging
* Amelioration should retard normal aging""" .
(:Aging_Hallmark :manifests_during :Normal_Aging) a :Aging_Hallmark_Criterion .
((:Experimental_Aggravation :of :Aging_Hallmark) :accelerates :Aging) a :Aging_Hallmark_Criterion .
((:Amelioration :of :Aging_Hallmark) :should_retard :Normal_Aging_Process) a :Aging_Hallmark_Crtierion .
:Chromatin_Hallmark rdfs:subClassOf :Hallmark .
:Genomic_Instalibity rdfs:subClassOf :Chromatin_Hallmark .
:Epigentic_Alterion rdfs:subClassOf :Chromatin_Hallmark .
:Metabolic_Hallmark rdfs:subClassOf :Hallmark .
:Proteostasis_Loss rdfs:subClassOf :Metabolic_Hallmark .
:Nutrient_Sensing_Deregulation rdfs:subClassOf :Metabolic_Hallmark .
:Mitochondrial_Dysfunction rdfs:subClassOf :Metabolic_Hallmark .
:Breakdown_Hallmark rdfs:subClassOf :Hallmark .
:Proteostasis rdfs:subClassOf :Breakdown_Hallmark .
:Stem_Cell_Exhaution rdfs:subClassO :Breakdown_Hallmark .
:Intercellular_Signaling_Alteration rdfs:subClassOf :Alteration .
# Nuclear DNA:
# Mitochondrial DNA:
:mtDNA_Damage rdfs:subClassOf :DNA_Damage .
:Heteroplasmy a :Phenomenon ;
:description "The multiplicity of the mitochondrial genomes allows the coexistence of mutant and wild-type genomes with the same cell." .
:Homoplasmy a :Phenomenon ;
owl:disJointClass :Heteroplasmy ;
:description "Despite the low level of mtDNA mutations, the mutational load of individual aging cell becomes significant and may attain a state of homoplasmy in which one mutant genome prevails [Khrapko et al., 1999]." .
:Mutation_Load rdfs:subClassOf :Load .
:Coexistence rdfs:subClassOf :Being ;
:definition "Existing peacefully together" .
:Replication_Error rdfs:subClassOf :Error .
:Polyclonal_Expansion rdfs:subClassOf :Expansion .
:Resipiratory_Chain_Dysfunction rdfs:subClassOf :Dysfunction .
:Multisystem_Disorder rdfs:subClassOf :Disorder .
:Mitochondrial_DNA_Polymerase_γ_Deficiency a :Deficiency ;
:description "Mice that are deficieny in mitochondrial DNA polymerase γ exhibt aspects of premature aging and reduced lifespan in association wtih the accumulation of random point mutations and deletions in mtDNA [Kujoth et al., 2005; Trifuncovic et al., 2004; Vermulst et al., 2008]. Cells of this mie exhibit impaired mitochondrial function, but unexpectly, this is not accompanied by increased ROS production [Edgar er al., 2009; Hiona et al. 2010]. Moreover stem cells from this progeroid mice are particularly sensitive to the accumulation of mtDNA mutations [Ahlqvist et al., 2012]." .
:Mitochondrial_Function_Impairment rdfs:subClassOf :Function_Impairment ;
:synonym "Impaired Mitochondrial Function" .
:ROS_Production_Increase a :Change ;
:synonym "Increased ROS Production" .
:mtDNA_Mutation_Accumulation rdfs:subClassOf :Cellular_Damage_Accumulation ;
:synonym "Accumulation of mtDNA Mutation" .
# Nuclear Architecture
:Nuclear_Lamina a owl:Class ;
:description "The nuclear lamina is a dense fibrous network on the inner periphery of the nucleus, where inhibitory proteins typically repress gene activity." .
:Nuclear_Lamina_Defects a :Defect .
:Nuclear_Lamin a owl:Class ;
:description "Nuclear lamins constitute the major components of the nuclear lamina nd participate in genome maintenance by providing a scaffold for tethering chromain and protein complexes that regulate genomic stability [Gonzalez-Suaraes et al., 2009; Liu et al., 2005]." .
:Participation a owl:Class .
:Genome_Maintenance a :Maintenance .
:Scaffold a owl:Class .
:Complex a owl:Class .
:Chromatin_Complex rdfs:subClassOf :Complex .
:Protein_Complex rdfs:subClassOf :Complex .
:Discovery a owl:Class .
:Protein_Component a owl:Class .
:Structure a owl:Class .
:Factor a owl:Class .
:Maturation a owl:Class .
:Dynamics a owl:Class .
:Nuclear_Lamina_Alteration rdfs:subClassOf :Alteration ;
:description "Alteration in nuclear lamina has been detected during normal human aging [Ragnauth et al. 2010; Scaffidi and Misteli, 2006]." .
:Progerin a :Protein ;
:synonym "Abberrant prelamin A isoform" ;
:description "Production of an aberrant prelamin A isoform called progerin has been detected during normal human aging [Ragnauth et al., 2010; Scaffidi and Misteli, 2006]." .
:Progerin_Production a :Age-Related_Change, :Production .
:A-type-Lamin rdfs:subClassOf :Nuclear_Lamin ;
:decline_during :Cell_Senescence .
:Lamin_B1 rdfs:subClassOf :Nuclear_Lamin ;
:decline_during :Cell_Senesecence .
:Telomere_Dysfunction rdfs:subClassOf :Dysfunction ;
:description "Telomere dysfunction promotes progerin production in normal human fibrblasts upon prolonged in vitro culture, indicating intiate links between telomere maintenance and progerin expression during normal aging [Cao et al., 2011]." ;
:promotes :Progerin_Production .
:A-Type-Lamin_Level_Decline a :Change ;
:description "A-type lamins levels decline during cell senescence, pointing to tis utility as biomarker of this process [Freund et al. 2012; Shimi et al., 2011]." .
:Lamin_B1_Level_Decline a :Change ;
:description "Lamin B1 levels declines during cell senescence, pointing to tis utility as biomarker of this process [Freund et al. 2012; Shimi et al., 2011]." .
# Telomere Attrition
:Multiprotein_Complex rdfs:subClassOf :Complex .
:Shelterin a :Mutliprotein_Complex ;
:description "Telomeres are bound by a characteristic multiprotein complex, shelterin [Palm and de Lange, 2008]. A main function of this complex is to prevent the access of DNA repair protein to the telomeres. Otherwise, telomeres would be ``repaired`` as DNA breaks leading to chromosome fusions. Duo to thier restricted DNA repair, DNA damage at telomeres is notably persistent and hghly efficient in inducing senescence and/or apoptosis [Fumagalli et al., 2012; Hewitt et al., 2012]." .
:Regenerative_Capacity rdfs:subClassOf :Capacity .
:Short_Telomere rdfs:subClassOf :Telomere .
# Epigenetic Alterations:
:Alteration a owl:Class .
:Epigenetic_Alteration rdfs:subClassOf :Alteration ;
:definition "Alterations in the methylation of DNA or acetylation and methylation of histones, as well as other chromatin-associated proteins, can induce epigenetic changes that contribute to the aging process." .
:Histone_Modification rdfs:subClassOf :Epigenetic_Alteration .
:H4K16ac rdfs:subClassOf :Histone_Modification .
:H4K20me3 rdfs:subClassOf :Histone_Modification .
:H3K4me3 rdfs:subClassOf :Histone_Modification .
:H3K9me rdfs:subClassOf :Histone_Modification .
:H3K27me3 rdfs:subClassOf :Histone_Modification .
:DNA_Methylation rdfs:subClassOf :Epigenetic_Alteration .
:Global_Methylation rdfs:subClassOf :DNA_Methylation .
:Local_Methylation rdfs:subClassOf :DNA_Methylation .
:Global_Hypomethylation a :Age-Related_Change, :Decrease ;
:description "There is an age-associated global hypermethylation." .
:Local_Hypermethylation a :Age-Related_Change, :Increase ;
:description "Several loic, including those corresponding to various tumor suppressor genes and Polymcomp target genes, actually become hypermethylated with age [Maegawa et al., 2010]." .
:Epigenetic_Defect rdfs:subClassOf :Defect ;
:synonym "Epimutation" ;
:description "Epigenetic defects or epimutations accumulated throughout life may specifically affect the behaviour and functionality of stem cells [Pollina and Brunet, 2011]." .
:Chromatin_Remodeling rdfs:subClassOf :Epigenetic_Alteration .
:Factor a owl:Class .
# :Chromatin_Remodeling_Factor a :Factor .
:Chromatin_Remodeler rdfs:subClassOf :Protein_Complex ;
:synonym "Chromatin Remodeling Factor" .
:HP1α rdfs:subClassOf :Chromatin_Remodeler .
:NuRD rdfs:subClassOf :Chromatin_Remodeler .
:Polycomp_Group_Protein rdfs:subClassOf :Chromatin_Remodeler ;
rdfs:subClassOf :Protein .
:Reversion_of_Epigenetic_Change rdfs:subClassOf :Reversion .
:Transcriptional_Noise rdfs:subClassOf :Noise .
:RNA_Processing_Aberration rdfs:subClassOf :Aberration .
:Impaired_DNA_Repair rdfs:subClassOf :Impairment ;
:synonym "Impaired_DNA_Repair" .
:Chromosomal_Instability rdfs:subClassOf :Instability .
:H4K16ac_Increase a :Epigenetic_Alteration, :Increase ;
:synonym "Increased H4K16ac" .
:H4K20me3_Increase a :Epigenetic_Alteration, :Increase ;
:synonym "Increased H4K20me3" .
:H3K4me3_Increase a :Epigenetic_Alteration, :Increase ;
:synonym "Increased H3KK4me3" .
:H3K9me_Decrease a :Epigenetic_Alteration, :Decrease ;
:synonym "Decreased H3K9me" .
:H3K27me3_Decrease a :Epigenetic_Alteration, :Decrease ;
:synonym "Decreased H3K27me3" .
:H3K4me_Decrease a :Epigenetic_Alteration, :Decrease ;
:synonym "Decresaed H3K4me" ;
:description "The loss of methylation of lysine 4 at histone H3 at gene promoters might be due to limited inheritance of this mark during replication [Joerg Galle, personal communication]." .
## Chromatin Remodeling
:Global_Heterochromatin_Loss a :Age-Related_Change, :Loss .
:Global_Heterochromatin_Redistribution a :Age-Related_Change, :Redistribution .
:Subtelomeric_Region rdfs:subClassOf :Region ;
:description "Subtelomeric regions show features of constitutive heterochromatin, including H3K9 and H4K20 trimethylation, HP1α binding, and DNA hypomethylation." .
:Heterochromatin_Formation rdfs:subClassOf :Formation .
:Heterochromatin_Assembly_at_Pericentric_Region a owl:Class ;
:description "Heterochromatin assembly at pericentric region requries trimethylation of histones H3K9 and H4K20, as well as HP1α binding, and is important for chromosomal stability [Schotta et al., 2004]." ;
:requires :H3K9me3, :H4K30me3, :HP1α_Binding ;
:important_for :Chromosomal_Stability .
:Chromosomal_Stability rdfs:subClassOf :Genomic_Stability .
:Repeated_DNA_Domain rdfs:subClassOf :Domain .
:Heterochromatin_Domain rdfs:subClassOf :Domain .
# Transcriptional Alterations
:Transcriptional_Alteration rdfs:subClassOf :Alteration ;
:synonym "Transcriptional Change" .
:Transcriptional_Noise rdfs:subClassOf :Noise .
:Increase_in_Transcriptional_Noise a :Age-Related_Change ;
:description "Aging is associated with an increase in transcriptional noise [Bahar et al., 2006] and an aberrant production and maturation of many miRNAs [Harries et al., 2011; Nicholas et al. 2010]." .
:Lysosomal_Degradation rdfs:subClassOf :Degradation .
# Reversion of Epigenetic Changes
:Histone_Acetyltransferase_Inhibitor rdfs:subClassOf :Inhibitor ;
:description "Inhibitors of histone acetyltransferases amerliote the premature aging phenotypes of progeriod mice and extend their lifespan [Krishnan et al., 2011]." ;
:extends :Lifespan .
:Parent a owl:Class .
:Descendant a owl:Class .
# Loss of Proteostasis:
:Chaperone rdfs:subClassOf :Protein .
:Proteostasis a :Cellular_Process .
:Impaired_Proteostasis a :Impairment .
:Impaired_Protein_Homeostasis a :Impairment .
:Control_Mechanism rdfs:subClassOf :Mechanism .
:Quality_Control_Mechanism rdfs:subClassOf :Control_Mechanism .
:Heat_Shock_Family rdfs:subClassOf :Protein_Family .
:Proteotaxocity rdfs:subClassOf :Toxicity .
:Protease rdfs:subClassOf :Enzyme .
:Misfolded_Polypeptide rdfs:subClassOf :Polypeptide .
:Altered_Proteotasis rdfs:subClassOf :Age-Related_Change ;
:description "Proteostasis is altered with aging [Koga et al. 2011]." .
:Unfolded_Protein rdfs:subClassOf :Protein .
:Misfolded_Protein rdfs:subClassOf :Protein .
:Aggregated_Protein rdfs:subClassOf :Protein .
# Chaperone-Mediated Protein Folding and Stability:
:Cochaperone a owl:Class .
# Proteolytic System
:Proteolytic_System rdfs:subClassOf :System .
:Autopagy-Lysosomal_System a :Proteolytic_System ;
:declines_with :Age ;
:reference "Rubinsztein et al., 2011" .
:Ubquitin-Proteosome_System a :Proteolytic_System ;
:declines_with :Age ;
:reference "Tomaru et al., 2012" .
:Lamp2a_Expression_Restoration a :Intervention ;
:description "Transgenic mice with an extra copy ot the chaperone-mediated autophagy receptor LAMP2s do not experience aging-associated decline in autophagic activity and preserve improved hepatic function with aging [Zhang and Cuervo, 2008]." .
:Mediator a owl:Class .
:Anti-Aging_Property rdfs:subClassOf :Property .
:Cue rdfs:subClassOf :Stimulation .
:Environmental_Cue rdfs:subClassOf :Cue .
:Survival a owl:Class .
:Individual a owl:Class .
:Body_Mass_Index rdfs:subClassOf :Index .
:Visceral_Fat rdfs:subClassOf :Fat ;
:is_associated_with :Proinflammatory_Cytokine ;
:interferes_with :Insulin_Action .
:Circadian_Rhythm :declines_with :Age .
:Molecular_Aggregate rdfs:subClassOf :Aggregate .
:Protein_Aggregate rdfs:subClassOf :Molecular_Aggregate ;
:of :Protein .
:Lipofuscin rdfs:subClassOf :Molecular_Aggregate ;
:description """As organisms age, they tend to accumulate insoluble, often pigmented matter inside their non-dividing cells. Lipofuscin, which accumulGerates most prominenlty in brain and cardiac cells, is one such age pigment. Lipofuscin and related speceis are the indigstible and highly cross linked debris of old mitochondria that have been reprocessed through the lysosomes of cells.""" .
:Lipofuscin_Accumulation rdfs:subClassOf :Accumulation ; # 008
:of :Lipofuscin ;
:in_the :Lysosome ;
:within :Postmitotic_Cell ;
:leads_to :Lipofuscin_Filled_Lysosome .
:Connective_Tissue_Mineralization rdfs:subClassOf :Mineralization .
:Amyloid a owl:Class ;
owl:equivalentClass <http://purl.bioontology.org/ontology/LNC/LP31745-0>, <http://purl.bioontology.org/ontology/MSH/D000682>, <http://bioonto.de/mesh.owl#D12.776.049> .
:Transthyretin_Amyloid rdfs:subClassOf :Amyloid .
:Stress_Adaptation rdfs:subClassOf :Adaptation ;
:synonym "Adaptation to Stress" .
:Advanced_Glycation_Endproduct rdfs:subClassOf :Endproduct, :Post-Translational_Modification ;
:acronym "AGE" ;
:description """Low amount AGE is good.
High amount of AGE is bad""" ;
:can_induce :Oxdiative_Stress, :Protein_Dysfunction, :Protein-Cross_Link, :Proinflammtory_Cytkine_Expression, :Apoptosis, :Inflammation ;
:is_considered_as :Aging_Biomarker ;
:is_associated_with :Cardiovascular_Disease ;
:is_product_of :Brown_Reaction ;
:accumulate_during :Aging ;
:inibits :Tumor_Growth ;
:may_prevent :Lung_Tumor_Growth . # in vitro in vivo
:Carboxymehtylisine rdfs:subClassOf :Advanced_Glycation_Endproduct .
# capacities posi
# beitraee fuer kausal processe
:Universal_Deterioriation_Process rdfs:subClassOf :Deteriation_Process ;
:such_as :Oxidation, :Wear_and_Tear ;
:causes (:Aging :in :Machinery), (:Aging :in :Exterior_Paint), (:Aging :in :Inanimate_Object) ;
:results_in :Aging ;
:is_believed_by :Scientist ;
:object :many ;
:is_believed_by :Public ;
:description "Many scientists and most of the public believe that aging is simpy the result of universal deterioation processes such as oxidation or wear and tear that cause aging in machinery, exterior paint, and other inaminate objects." .
:Inanimate_Object rdfs:subClassOf :Object ;
:is :inanimate .
:Adult_Organism rdfs:subClassOf :Organism .
:Reaction_Time rdfs:subClassOf :Time ;
:of :Reaction ;
:may_slow_with :Age .
(:Knowledge :of :World_Event)
:may_expand_with :Age .
:may_expand_with :Age .
:Cultural_Convention rdfs:subClassOf :Convention ;
:is :cultural .
:Societal_Convention rdfs:subClassOf :Convention ;
:is :societal .
(:Quantity :of :Hematopoietic_Stem_Cell)
:decline_with :Aging .
:geriatric a :Object_Modifier ;
:definition "of or relating to the aged" .
:pediatric a :Object_Modifier ;
:synonym "peadiatric" ;
:definition "of or relating to the medical care of children" .
<https://www.researchgate.net/post/At_what_age_are_laboratory_mice_considered_adult2> a :Web_Thread ;
dc:title "At what age are laboratory mice considered adult?" .
<http://embor.embopress.org/content/6/11/1006.long> a :Commentary ;
dc:title "Science fact and the SENS agenda" ;
:subtitle "What can we reasonably expect from ageing research?" .
<https://futurism.com/it-was-only-a-matter-of-time-scientists-found-a-way-to-reverse-signs-of-aging/> a :News_Report ;
dc:title "It Was Only a Matter of Time: Scientists Found a Way to Reverse Signs of Aging" .
pmid:27984723 a :Journal_Article ;
dc:title "In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming." .
Ageing is one of the oldest biological enigmas and a major biomedical problem of the 21st century. Ageing is an almost ubiquitous though not universal phenomenon in nature. It has been a research puzzle for decades as too why lifespan is limited and evolution has not eliminated the phenomenon. To understand ageing it is important to define it as precisely as our current understanding will allow. However, a consensus on a simple definition of ageing has not been achieved, evidence of the lack of an understanding of the mechanisms underlying the ageing process [Li+Al:2014].
Increase in Probability of Death. Ageing is an increased liability to die, or an increasing loss of vigour, with increasing chronological age, or with the passage of life cycle [Comfort:1960]. Ageing is accompanied by deteriorative changes with time during postmaturational life that underlie an increasing vulnerability to challenges, thereby decreasing the ability of the organism to survive [Masoro:1995]. The ageing process renders individuals more susceptible as they grow older to the various factors, intrinsic or extrinsic, which may cause death [Maynard:1962]. Ageing can be defined as the increase in the probability of death within a period of time. In humans, from 0 to 9 years there is decrease in the probability to die in the following year. After age nine the age-specific mortality rate increases and there is an exponential increase in this rate from around 30 years [Arking:2006]. Ageing therefore seems to be a natural phase in many organism's life cycle.
Natural Deterioration. Ageing is observed natural deterioration of bodily functions, organs, and organ systems increasing the onset of disease and pathology, with a resulting loss of function eventually leading to death.
Functional Decline. By teleological criteria, development can be viewed as consisting of early processes that enhance the functional capacity of a system, whereas ageing consists of later processes that diminish or have no effects on ability to function [Kohn:1978]. Ageing is the progressive decline in several but not all physiological functions, resulting ultimately in the thermodynamic equilibrium, i.e. death. Ageing decreases most aspects (functionalities), although some kinds of cancer are less severe in elderly people as a result of diminishing rates of mitosis. Therefore defining ageing simply as functional decline is not sufficient.
Passing of Time. Ageing is generally used to describe a host of time-related alterations in biological entities from molecules to ecosystems [Finch:1990]. Ageing is a progressive, i.e. a time-dependent phenomenon. Ageing is (for a normally developing organism) just the passing of time. It starts when the survival probability curve has reached its maximum (i.e. lowest age-specific mortality rate) and ends with death. However, ageing is fundamentally an event-dependent phenomenon, rather than a time-dependent process [Arking:2006]. Physiological biomarkers are a much more useful index of ageing than is the simple passage of time [Arking:2006].
Ageing as a Disease. Is ageing a disease? Disease is very much a social construction that takes into account statistical data and available therapy. Regarding statistics, ageing is not a disease because it affects all individuals of a species. Statistically speaking, it is a common feature of most living beings. Regarding available therapy and symptoms, the rate of ageing can be modified but the process is not yet treatable, as all humans eventually die and if they are lucky they die of old age, i.e. the result of ageing.
Developmental Process Usually each human follows the same path of growth, development, maturity and senescence [Arking:2006]. The changes from maturity through senescence constitute the ageing process [Rothstein:1982]. All the parts of the life cycle are continuous with one another in process and mechanism [Arking:2006]. Ageing is a naturally developing biological process which limits the adaptive possibilities of an organism, increases the likelihood of death, reduces the lifespan and promotes age pathologies [Frolkis:1982].
Overall, ageing is a process, that involves changes of the structure of an organism. It is multi-factorial and multi-dimensional at its root, occurs gradually, but is degenerative in its consequences as it leads to loss of functionality and ends with death. Ageing could be defined as every irreversible change of living substances as a function of time [Smith:2002], but are all those processes really irreversible? This seems not to be the case. Most definitions of ageing acknowledge that it is related to changes in the organism leading to a loss in adaptability. This loss in adaptability leads to a higher chance of death. Ageing is a time-independent series of cumulative, progressive, intrinsic, and deleterious function and structural changes that usually begin to manifest themselves at reproductive maturity and eventually culminate in death [Arking:2006].
It is important to measure ageing, the rate of ageing and the process of ageing. Otherwise it would not be possible to know whether an organism ages faster or slower than others. Nor would be possible to know whether an anti-ageing intervention is actually working. In practice two different measurement standards are used dependent on whether ageing is measured in a population or in an individual [Arking:2006].
Ageing in population is measured by using the observed age-specific mortality rates to calculate the number of surviving organisms that will likely die in the next time period. On a demographic level ageing is associated with increased mortality with increasing age as well increased susceptibility to age-related disease. If the death number increases, then the population is composed of ageing individuals, i.e. ageing population. The rate of ageing can be calculated based on how long it takes for the mortality rate to double [Arking:2006].
In individuals, ageing is measured by documenting changes in physiological traits, or biomarkers, known to be important to normal functioning and capable of predicting remaining lifespan. The search for such biomarkers of ageing is an important quest of biogerontology. Biomarkers of ageing are usually surrogates of mortality statistics. None have been shown to be predictive of future survival that are better than the age of the individual. A combination of multiple biomarkers (like derived from genomics or other omics) utilized by mathematical models might have the potential to overcome this, e.g. epigenetic markers are promising candidates for being able to reliably predict future mortality [Christiansen+Al:2016]. In the case the observed changes are altered in the direction of loss of function, then the individual is ageing at some calculable rate of loss of function [Arking:2006].
Although ageing is quite widespread across species - it is not a universal phenomenon. Ageing is actually an incredibly plastic process which can be sped up (e.g. by mutation), slowed down (e.g. by dietary restriction), totally stopped (e.g. by genetic knockout), or even reversed (e.g. by overexpression of genes) [Berger:2014] [de_Magalhaes:1997]. The exact mechanism of ageing is an enigma. Understanding why certain species exhibit ageing and others do not (negligible senescence and biological immortal species) would revolutionize medicine.
Although defining what exactly is ageing is difficult, yet it is possible to measure it at least reliable on the population level. From this it is clear that the ageing process is quite plastic, which means it varies from species to species and from individual to individual within a species. In fact, there are quite large intraspecies and even bigger interspecies differences in the lifespan of an organism and the rate of ageing. The rate of ageing varies substantially across different species. This is mainly because of genetic differences. Some species live just about a day (e.g. mayfly), while others live centuries (e.g. sharks, whale). Yet other do not appear to have age-related changes, i.e. exhibit negligible senescence (rockfish, lobster, turtle, etc.), and there are even species which have been declared to be immortal (sea squirts, jellyfish, hydra, flatworms, etc.). The naked-mole rat might be the first mammal that has been declared to exhibit negligible senescence. Although it lives 9 times longer than similar-sized mice and only shows slight age-related changes with no decline in fertility nor was it observed to develop any spontaneous neoplasm [Buffenstein:2008], the naked mole rat dies still of old age
Ageing within a population is not uniform either. There is a genetic heterogeneity as well as environmental influences that lead to a profile of different lifespans.
The ageing process within a single organism can be altered. In particular the genetic makeup and epigenetic modifications play an important roles, i.e. genes and their activities affect the ageing process. A variety of alterations in specific genes can extend lifespan quite substantially in model organisms and under laboratory conditions. Those increases are dramatic in simple budding yeast and nematodes, less so in fruit flies and less again in rodents.
Manipulating just single genes can accelerate ageing or slow down ageing hence greatly extend lifespan like up to 10-fold [Shmookler_Reis+Al:2009]. It has been demonstrated that it is possible to reverse ageing, even by simple ectopic overexpression of just single transcription factor out of two (IME1 and NDT80) in a model organism such as Saccharomyces cerevisiae [Unal+Al:2011]. In humans single gene mutations can lead to accelerated ageing (progeroid syndromes). On the other hand, many genetic differences were found to be associated with longevity in centenarians and some in supercentenarians [Fortney+Al:2015].
Ageing genes appear to be extremely conserved across species. For example, the sirtuin family of genes has a significant effect on the lifespan in many organisms. Their effect seems to be strong in yeast [Kaeberlein+Al:1999] and nematodes [Tissenbaum+Guarente:2001], and weak in fruit flies [Rogina+Helfand:2004] and mice [Price+Al:2012]. Further a substantial number of non-genetic interventions including single compounds were found to affect ageing and extend lifespan [Vaiserman+Al:2017].
Ageing is a widespread and almost ubiquitous phenomenon that affects virtually all biological species. For species that age, ageing appears to affect most aspects of an organism in a negative manner and increases its probability of health problems and death with increasing age. Though people live longer today through medical and safety improvements, the ageing process itself still leads to age-related disabilities and causes increasing physical, psychological, and economic burdens.
While ageing has been an inevitable phenomenon for centuries, it now becomes more and more of a problem that can be understood (by science) and solved (via technology). Not only could ageing be solved as a theoretical problem, but it could also be treated as a medical condition.
However, the precise mechanisms of ageing remain largely unknown. Despite advancements in understanding the mechanisms of ageing (from a "backwater" of biology, full of anecdotes, to a serious discipline) and the possibility to interfere with the ageing process by changing just a single gene, applying dietary interventions (even with a single type of molecule) [de_Magalhaes+Al:2012] or simply repairing the damage (via regenerative medicine), the actual evolutionary theory ("why") and molecular/physiological mechanism ("how") of ageing remains unknown. To understand the biology of ageing requires posing testable and reasonable questions like [Arking:2006]:
Some anti-ageing mechanisms are species-specific (private mechanisms), others appear to be highly conserved across phylogenetic lines (public mechanisms). In the latter case, insights obtained from investigations on one species of laboratory organism can be translated to rodents or to primates and perhaps humans. Although all ageing mechanisms are of particular interests, conserved mechanisms have the greatest significance because they may imply possible interventions into human ageing.
Biology does not deal only with mere facts, but rather with developing an understanding of underlying mechanisms. There are three types of evidence [Arking:2006]:
Loss-of-function and gain-of-function are quite common approaches in genetics, while correlative evidence is dominating genomics.
Correlative evidence is derived from observed temporal or spatial correlations between two or more events.
Loss-of-function evidence is based on deactivation of an entity, e.g. the inactivation of a gene by knock-out or knock-down.
Gain-of-function is the strongest type of evidence in which some technique is used to specifically increase the activity of an entity. All three types of evidence are used to infer causality among events, while it is challenging for correlative evidence, causation is more likely to be inferred from loss-of-function and especially gain-of-function data. However uncertainty of inference remains.
While humans died in the past mostly in the perinatal period (i.e. death in the first five years of life) or due some infectious disease, today people suffer from age-related diseases and more than 100,000 individuals die daily due to the consequences of the ageing process, either directly (as a primary cause via age-related diseases) or indirectly (as contributory cause due to reduced functionality) [de_Grey:2007] [YourTribute:2013].
Ageing is the underlying cause of almost all major human diseases, such as atherosclerosis, cancer, cardiovascular defects, catarct, diabetes-2, dementia, macular degeneration, neurodegeneration, osteoporosis and excessive muscle loss leading to sarcopnia [Rattan:2007] [Holliday:2017]. Ageing is by far the leading cause of death (though it acts mostly indirectly and in a gradual manner). Of the 150,000 people dying every day, two thirds die of age-related disease. The proportion is even higher in industrialized nations where it is reaching 90% [de_Grey:2007].
Ageing is directly associated with numerous age-related diseases (e.g. neurodegeneration, metabolic and cardiovascular disease, cancer, etc.) and the single risk factor common to all of the leading causes of death is age [Hayflick:2007] [Fontana+Al:2014]. Therefore the research in animals and humans should be refocused to find ways to prevent and treat ageing [Fontana+Al:2014]. Slowing down the ageing process by even the slightest degree could dramatically increase the general health much more than the elimination of any single disease. Hence understanding ageing as the root cause of many diseases would be far more efficient than tackling age-related diseases one-by-one [Hayflick:2007] [Fontana+Al:2014].
If ageing could be slowed down even slightly the improved health of humans and the economic benefit would be significant.
The research on numerous diseases has demonstrated that an underlying risk factor for many illnesses is age. In fact, the single risk factor common to many diseases is age. The susceptibility to the effects or severity of a disease is significantly modified by ageing. Further, chronological age is the most important risk factor for the development of diverse disease, including degenerative diseases and cancer [Brett+Rando:2014]. Ageing causes disease and loss of function that in turn causes death. The difficulty with this statement is that one is more or less forced into defining the boundary where the disease or loss-of-function begins, which is almost impossible because it always begins very subtly. It is therefore useful to define ageing as the über-disease encompassing all late-life dysfunction, such that disease and functional deficits of old age are simply facets of the later stages of ageing - they are part of ageing rather than being distinct from it. Thereby ageing does directly cause death, and one can subdivide the specific sequences of events that lead to death in a given individual.
Whether ageing should be acknowledged as a disease is debatable [Gems:2015] [Bulterijs+Al:2015]. Arguments for this acknowledgement are that 1) ageing actually fits very well most definitions of disease, and 2) this acknowledgement could have an impact on making it easier to develop anti-ageing drugs.
On the contrary, one of the arguments against defining it as a disease is that it is almost universal, i.e. it seems to occur in every member of a species. However this universality is questionable as there exist species that do not appear to show population ageing. Another counter-argument is that it is normal as it occurs in every human, while disease is more often associated with abnormality. However, an infectious disease, like one caused by a virus, could theoretically affect most or even all individuals of a population or perhaps a species. Although having this disease is the norm, it is still a disease. Quite often ageing is semantically understood as a neutral term (especially in English) that just means the passage of time and includes development. However, it still has a negative sentiment and often refers to the later phase of life that is associated with deterioration which some people refer to as senescence. One could also argue that there is no point in calling something a disease as it can not yet be treated. But this is not true as there are already interventions that counteract ageing and on the other hand there are also diseases that have not yet any cure and can not really be treated. Others argue often that ageing-related changes are not always negative and that it also has positive aspects. Overall this does not hinder its classification as a disease as diseases are also associated with certain changes that have no negative influences (or are not known to be negative). Sometimes the complexity and heterogeneity of the phenotypes or symptoms of ageing are used as a counter-argument to classifying ageing as disease, because diseases often have very well-defined symptoms. This argument ignores the heterogeneity of humans themselves and the fact that a disease also affects individuals differently depending on their genetic disposition and lifestyle as well as environment. Yet, another argument states that ageing requires research on things that maintain health and everything that increases health counteracts ageing. The truth is even when living as healthily as possible by any current recommendations individuals will still age and die.
If ageing was to be declared as a disease, it would have little effect on the scientific quest of seeking the underlying molecular mechanisms that cause and control the rate of ageing, it may however make it easier to develop drugs that counteract ageing as an indication rather than some specific age-related diseases.
Overall there are no contradictions in defining ageing as a disease, although ageing IS NOT a single disease as it manifests itself in many different sub-diseases. It is somehow an Überdisease. It is the root cause and major risk factor of many diseases. One can conversely view each age-related disease as only one symptom of the overarching master disease commonly referred to as "ageing". Even if one symptom could be cured the next age-related disease would strike soon as long as its main underlying causative mechanism, i.e. ageing, is not addressed.
There are myriads of changes happening during ageing but only few might be the drivers of the process while others are merely symptoms.
Ageing is not simply the sum of the aggregate pathologies and of disease-induced changes, and conversely, not all the changes in structure and function that are correlated with age may be appropriately considered as fundamental age-related changes (causes) per se. A fundamental age-related change must meet the following four conditions [Strehler:1982]:
However the concept of universality seems to be invalid as there is so much individual variation in ageing due in part to our genetic heterogeneity and in part to chance alone [Finch+Kirkwood:2000] that it is not possible for all members of a species to exhibit ageing in an identical manner. The concept of intrinsic change, while being valid, is being narrowed in light of the fact that various lifestyle practices modulate events that were assumed to be completely intrinsic. Nonetheless the concept of deleterious progressive and intrinsic changes is useful, such as in the investigation of stem cell ageing.
Cellular senescence is an irreversible growth arrest that may be an evolved anti-tumour mechanism. Senescence is a natural mechanism restricting propagation of cells, which passed through genotoxic or oncogene stresses, by epigenetic reprogramming. It is a kind of program or a state, basically subroutine, which the cell adapts after damage, stress or some kind of damaging signal. Senescence is a general purpose mechanism that is used for repair systems. Cellular senescence prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing [Baker+Al:2016]. It is a primitive and very ancient process that even occurs in single cellular organism.
Cellular senescence is induced by short telomeres (replicative senescence), but it can also be induced by various stressors (stress-induced premature senescence). There are more than 50 oncogenic or mitogenic alterations that are able to induce senescence [Gorgoulis+Halazonetis:2010].
There are certain phenotypes associated with the state of cellular senescence such as obvious morphological changes. Senescence cells enlarge and become resistant to apoptosis. Cellular senescence is frequently characterized by the expression of the p16 protein. There is also the formation of senescence-associated heterochromatin foci.
Cellular senescence exhibits a distinctive secretory phenotype [Baker+Al:2016]. This associated secretion profile (Senescence-Associated Secretory Phenotype; SASP) of senescence cells depends on the type of insult. Senescence markers show already up during development. However senescence cells accumulate in various tissues/organs over time [Baker+Al:2016]. It is a growth arrest that for some reason occurs because either the cell is damaged or due to some regenerative response. The type of profile of secretion depends on the context of damage/triggering signalling.
It is commonly believed that cellular senescence underlies organismal senescence in mammals.
There are many possible mechanisms involved in ageing. Over the last decades, theories about ageing have emerged and faded. The true nature of the ageing process however, is still uncertain. What is exactly happening on a biochemical, genetic, and physiological level still remains to be understood. What we see in an ageing person is a great deal of change in appearance, a decline in overall fitness and an increased chance of getting age-related diseases. These are, however, only the visible sides of the changes that start at the molecular level, then the cellular level, then progress to the tissue and organ level until in the end the whole physiology is affected. What are these processes that result in ageing? Although ageing is undoubtedly complex, it may be regulated by common mechanisms that are simpler than the effects they produce [Arking:2006].
Defining ageing clearly is challenging. Our understanding of how and why we age will originate from the study of the processes that happen in the cell and observable biological markers of ageing.