Table 2.
Multiple models to study aging
| Model type | Model name | Description |
|---|---|---|
| In vitro models | ||
| Replicative senescence (RS) | Replicative senescence model375,376 | Reduced saturation density, heightened cell surface area and volume, cell cycle arrest, shortened telomeres, and an increased occurrence of SA-β-gal positive staining |
| Chemotherapy-induced senescence (CIS) | hydroxyurea induced model377 | Increased ROS and SA-β-gal positive staining and decreased cell proliferation |
| Aβ1-42 oligomers model (AD model)378,379 | Increased ROS and SA-β-gal positive staining, PAI-1 and p21 mRNA levels, and decreased SIRT1 | |
| D-galactose model299 | Increased ROS, SA-β-gal positive staining, inflammation level, P16, P21 and P53 genes, and decreased of NRF2 and HO-1 | |
| Doxorubicin (a DNA topoisomerases inhibitors)380,381 | Cell cycle arrest, DNA damage, telomere shortening, increased expression of p16lnk4a | |
| Palbociclib treated (a CDK4/CDK6 inhibitor)382 | G0/G1 arrest, growth arrest, reduced Rb expression, increased SA-β-gal positive staining, and IL-6, IL-8, CXCL1 secretion | |
| Stress induced premature senescence (SIPS) | X-ray induced model383,384 | Irreversible G1 cell cycle arrest, DNA damage, increased SA-β-gal positive staining, IL-1β, IL-6, IL-8 and other SASP cytokines |
| UVB induced model385 | Growth arrest, increased SA-β-gal positive staining, senescence-associated gene overexpression, deletion in mitochondrial DNA | |
| H2O2 induced premature senescence386,387 | Increased SA-β-gal positive staining, irreversible G1 cell cycle arrest, telomere shortening, and increased p21 and gadd45 expression | |
| Tert-butylhydroperoxide (t-BHP) induced premature senescence model388 | Growth arrest, increased SA-β-gal positive staining, the presence of the common 4977-bp mitochondrial deletion, overexpression of p21waf-1 and the subsequent inability to phosphorylate pRb, increased senescence-associated genes expression | |
| Ethanol induced premature senescence model389,390 | Growth arrest, increased SA-β-gal positive staining, overexpression of p21waf-1 and the subsequent inability to phosphorylate pRb, the presence of the common 4977-bp mitochondrial deletion, increased senescence-associated genes expression | |
| Hyperoxia induced model391,392 | Irreversible G1 cell cycle arrest, telomere shortening, increased protein degradation, increased lipofuscin/ceroid formation, and accumulation | |
| Oncogene-induced senescence (OIS) | Mos-overexpression model393 | The growth arrest DNA damage, upregulation of p16INK4a, and increased SA-β-gal positive staining |
| B-RAF V600E model394,395 | Cell cycle arrest, upregulation of p16INK4a, and increased SA-β-gal positive staining | |
| H-RAS G12V model396,397 | Upregulation of p16INK4a, low phosphorylated Rb, increased SA-β-gal positive staining | |
| DNA methyltransferases inhibitor | 5‐aza‐2′‐deoxycytidine induced model | Growth inhibition, increased SA‐β‐gal,398 increased p16, decreased p53399 |
| Telomerase activity inhibitor | SYUIQ-5 induced model | Growth inhibition, increased SA‐β‐Gal, increased p16, p21, p27400 |
| Cyclin E overexpression model401,402 | Cell cycle arrest, DNA damge, and increased SA-β-gal positive staining | |
| IMR90 ER: RAS model403 | The growth arrest, increased SA-β-gal positive staining and SASP markers | |
| Elder donors derived aging models | iPSC-derived neuron with senescence phenotype404,405 | iPSC-derived neurons from elder donors have senescence-related gene expression |
| Induced neuron with senescence phenotype406,407 | Induced neurons from fibroblast of elder donors have age-dependent transcriptomic signatures | |
| In vivo models | ||
| SAMP models | SAMP6 (senile osteoporosis model)408–410 | Decreased bone formation, and increased bone marrow adiposity, proliferator activator γ (PPARγ), and crimp-related protein 4 (Sfrp4) |
| SAMP8 (AD model)301 | Age-related learning and memory deficits, amyloid-β deposition, abnormal autophagy activity | |
| SAM10 (neurodegenerative disease model)411 | Spontaneous brain degeneration leading to impairments in learning and memory as well as emotional disturbances | |
| Physicochemical induced aging model | D-Galactose induced model299,412 | Increased ROS, SA-β-gal positive staining, inflammation level, apoptosis, up-regulations of P53 and P21 genes expressions, and mitochondrial dysfunctions |
| D-galactose and AlCl3 induced AD model413 | Memory deficit, neuronal damage and caspase-3 overexpression in the hippocampus | |
| D-galactose and NaNO2 induced AD model414 | Increased oxidative stress, neuronal damage in the CA1, CA3, and CA4 regions of the hippocampus, impaired cognitive function, memory impaired, deterioration of sperm quality and testicular morphology | |
| AlCl3 induced model413,415 | A notable decline in cognitive function characterized by impaired short-term memory, heightened anxiety, and a decline in spatial and reference memory | |
| iron radiation induced model416 | Increased SASP marker, SA-β-Gal, IL-8 and persistent DNA damage responses | |
| O3 induced model | Including thymic atrophy, decreased body weight and exploratory activity, and increased oxidative damage | |
| Premature aging models (WS) | Wrn−/− Terc−/− model417 | Changes associated with aging include the shortening of telomeres, the onset of hair graying, alopecia, cataracts, malignancies, osteoporosis, and type II diabetes |
| WrnΔhel/Δhel model412 | Severe cardiac interstitial fibrosis, insulin resistance, hypertriglyceridemia, increased ROS, oxidative DNA damage, cancer incidence, and shortened lifespan | |
| Premature aging models (HGPS) | LmnaL530P/L530P model418 | Severe growth retardation, hair loss, osteoporosis, muscle atrophy |
| LmnaHG/+ model419 | Slow growth, osteoporosis, hair loss, partial fat malnutrition | |
| LmnaG609G/G609G model420 | Infertility, weight loss, growth retardation, spinal curvature, calcification of blood vessels, decreased bone density, and insulin-like growth factor | |
| Zmpste24-/- model421 | Dilated cardiomyopathy, lipodystrophy, muscular dystrophy, severe growth retardation, and premature death, | |
| Other premature aging phenotype | BubR1H/H model422 | Gliosis in the brain, arrhythmias, cataracts, hunchbacks, lipodystrophy, thinning of the skin, impaired vascular elasticity and fibrosis, and shortened life expectancy |
| Ndufs4−/− model (a progressive neurodegenerative phenotype with leigh syndrome)423 | Lethargy, ataxia, weight loss, premature death | |
| ERCC1−/− or Δ/− model424,425 | Growth retardation, ataxia, loss of visual acuity, cerebellar hypoplasia, encephalopathy, kidney failure, proteinuria | |
| Sod1−/− model426 | Muscle atrophy, fat metabolism disorders, hearing loss, cataracts, thinning of the skin, and defects in wound healing | |
| Klotho−/− model427,428 | Arteriosclerosis, cardiovascular injury, infertility, short lifespan, skin atrophy, osteoporosis, and emphysema | |
| XpdTTD/TTD model429 | Early graying, osteoporosis, cachexia, kyphosis, osteosclerosis, sterility, and shortened lifespan | |
| PolG model (mutation in mtDNA Polγ)430,431 | Alopecia, anemia, weight loss, hearing loss, reduced bone mineral density, and cardiomyopathy | |
| PolgAmut/mut model432 | Anemia, enlarged heart, osteoporosis, spine curvature, and reduced fertility | |
| Nfkb1−/− model303 | Shortened lifespan, kyphosis, osteoporosis, tissue inflammation, and gliosis of the central nervous system | |
| Terc−/− model433,434 | Shortened lifespan, reduced fertility, tissue atrophy, and impaired organ functions | |
| 3xTg-AD model (AD model)435,436 | Memory impairment, cognitive deficits, synaptic dysfunction, abnormal hyperexcitation of hippocampal neurons, amyloid plaques, and p-Tau accumulation | |
| Tg2576 model (AD model)437,438 | Cognitive impairment, memory loss, oxidative lipid damage and inflammation in the brain | |
| Longevity models | Naked mole-rats439,440 | As they age, no significant increase in mortality is observed and they retain basic physiological function. They age with health and this anti-aging properties make them as a good model for aging research. |
| Planarians309 | With significant regenerative powers, planarians are considered immortal, DNA efficient repair mechanism, strong telomerase activity | |
| Salamander | Strong ability to regenerate, clearance of senescent cells, | |
| Turtle | Clearance of ROS, strong telomerase activity, Efficient DNA repair mechanism | |
| Transgenic delayed aging model | Ames dwarf mice (Prop1df/df) | Prop1 gene recessive point mutation, impaired pituitary development smaller body size, PI3K/Akt/mTOR pathway downregulation441 |
| Snell dwarf mice (Pit1dw/dw) | Pit1 gene spontaneous mutations, impaired pituitary development, smaller body size, reduced immunosenescence442 | |
AD Alzheimer’s disease, WS Werner syndrome, HGPS Hutchinson-Gilford progeria syndrome, ERCC1−/− or Δ/− represents mutation and/or deletion in the Ercc1 gene, UVB ultraviolet B, B-RAF V600E valine is substituted for glutamic acid, IMR90 ER RAS model: IMR90 human primary fibroblast is infected with a 4-hydroxy-tamoxifen (4-OHT) inducible ER:RAS construct, where H-RASG12V is fused to a mutant form of the estrogen receptor (ER) ligand binding domain. PolgAmut/mut mutations in mtDNA PolgA, LmnaHG/+ farnesylated uncleaved form of LMNA, SAM senescence-accelerated mouse, SAMP senescence-prone inbred strains, SAMR senescence-resistant inbred strains, SASP senescence-associated secretory phenotype, WrnΔhel/Δhel helicase mutation in Wrn gene, XpdTTD/TTD: mutation of Xpd gene in the human disorder trichothiodystrophy (TTD), BubR1H/H mutations in BubR1 hypomorphic alleles