Abstract: Cell senescence is the biological process during which cell death is induced by the gradual loss of normal structure and function. This process is related to many fields like anti-aging research and cell therapy. Cell senescence can be induced by many factors, including stimulation of internal signaling pathway, free radical damage, gene expression changes and environmental change of extracellular matrix. These factors can affect cell life cycle and function.
Keywords: Cell Senescence and Aging, Cell Death, Anti-aging Research, Cell Therapy, Cellular Senescence Pathway
1. Types of Cellular Senescence
(1) Replicative cellular senescence: Cell division causes the reduction of telomere. When telomere reaches the limitation(Hayflick), cells activate aging program;
(2) DNA damage induced-cellular senescence: irreversible DNA damage induced-cellular senescence;
(3) Oncogene induced-cellular senescence: Activated oncogene(e.g. Ras, BRAF) or inactivated tumor suppressor genes induced-cellular senescence;
(4) Oxidative stress induced-cellular senescence: senescence caused by oxide or oxidant(e.g. hydrogen peroxide) derived from cell metabolism;
(5) Chemotherapy induced-cellular senescence: anti-tumor drugs induced-cellular senescence;
(6) Mitochondrial dysfunction induced-cellular senescence: mitochondrial disorder induced-cellular senescence;
(7) Epigenetics induced-cellular senescence: senescence caused by DNA methyltransferase inhibitor or histone deacetylase inhibitor;
(8) Paracrine senescence: senescence-associated secretory phenotype(SASP) induced-cellular senescence.
2. Senescence-associated Secretory Phenotype(SASP)
Features of aging include systemic chronic inflammations with cellular senescence, immunosenescence and organ dysfunction. Factors secreted by senescent cells are called senescence-associated secretory phenotype(SASP). These factors can promote chronic inflammation and induce senescence of adjacent cells. SASP diffuses to accelerate senescence and related diseases via autocrine and paracrine, including various factors such as cytokines, chemokines and growth factors. Researches show changes of these factors between normal and aging condition are obvious. The secretion increases during aging process.
3. Cellular Senescence Pathway
Seen from genetics, epigenetics, mRNA and protein level, currently cell senescence has recognized 6 key signaling pathways.
3.1. Genetics and Epigenetics
p16-Rb pathway: This pathway is involved in cell cycle regulated genes like p16 and Rb. In senescent cells, the increased expression of p16 and changes of Rb protein activity affect cell cycle to cause senescence.
p53-p21 pathway: p53 is the important tumor suppressor gene. p21 is the downstream gene. Accumulation of damage activates p53 and induces the expression of p21. p21 inhibits cell cycle progression and promotes cellular senescence.
3.2. mRNA Level
mTOR signaling pathway: mTOR is the key factor for regulating cell growth and metabolism. In senescent cells, the activity of mTOR excessively increases to cause irregularity of cell growth and promote aging.
AMPK signaling pathway: AMPK is the kinase sensing cellular energy status. During deficiency of energy, AMPK is activated to inhibit mTOR signaling pathway and promote cell aging.
3.3. Key Pathways of Cellular Senescence in Protein Level
SASP pathway: SASP refers to senescence-associated secretory phenotype, and is chemokine and inflammatory factor secreted by aging cells. These factors can result in inflammation and tissue damage to accelerate aging of cells and tissues.
Autophagy-lysosome pathway: This is the important pathway for recycled substances in cells. With the development of aging, the decreased activity of autophagy-lysosome pathway results in accumulated intracellular substances to promote cellular senescence.
4. Potential Anti-aging Drugs
In recent years, researches on aging mechanism promote strategies of disease prevention, and have found various small molecular compounds and potential anti-aging drugs for increasing life, e.g. metformin, rapamycin, spermidine, Senolytics drugs, Sirtuin activator and NAD+ prodrug etc. These compounds show their potentialities in increasing life and improving aging markers. However, most of them still require for clinical trial and pharmacodynamic validation in human body.
4.1. Changes of Aging-related Molecules
SA-β-gal: This is the common cell senescence marker widely applied in aging research.
Molecular Markers of Cell Cycle: One of cell senescence features is permanent cell-cycle exit in which many proteins play an important role, e.g. p14, p16 and p21 etc. Proteins coded by genes(like CDKN2A and CDKN1A) are main driving factors.
Other Markers(p53, p27, Rb): When judging whether cells are senescent, various features are required for consideration and analysis.
4.2. Potential Research on Cell Senescence in the Future
(1) Exploration for induced factors, markers, regulatory factors and signaling pathway;
(2) Analysis of specificity and differences among various tissues and organs;
(3) Penetration of cell senescence mechanism during physiological and pathological process, and interaction with other cells and microenvironment;
(4) Development of effective and safe detection method for removing senescent cells;
(5) Evaluation of effects on tissue functions and general health;
(6) Improvement of effects on aging-related diseases, cancer and regenerative medicine via using cell senescence as the therapeutic target.
5. Recommended Products
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Target |
Antibody |
Recombinant Protein |
ELISA Kit |
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IL-6 antibody |
IL-6 recombinant protein |
IL-6 ELISA Kit |
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IL-7 antibody |
IL-7 recombinant protein |
IL-7 ELISA Kit |
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IL-13 antibody |
IL-13 recombinant protein |
IL-13 ELISA Kit |
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IL-15 antibody |
IL-15 recombinant protein |
IL-15 ELISA Kit |
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IL-18 antibody |
IL-18 recombinant protein |
IL-18 ELISA Kit |
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IL-1β antibody |
IL-1β recombinant protein |
IL-1β ELISA Kit |
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MMP-1 antibody |
MMP-1 recombinant protein |
MMP-1 ELISA Kit |
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MMP-3 antibody |
MMP-3 recombinant protein |
MMP-3 ELISA Kit |
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MMP-10 antibody |
MMP-10 recombinant protein |
MMP-10 ELISA Kit |
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MMP-12 antibody |
MMP-12 recombinant protein |
MMP-12 ELISA Kit |
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MMP-13 antibody |
MMP-13 recombinant protein |
MMP-13 ELISA Kit |
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TNF-α antibody |
TNF-α recombinant protein |
TNF-α ELISA Kit |
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VEGF antibody |
VEGF recombinant protein |
VEGF ELISA Kit |
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PDGF antibody |
PDGF recombinant protein |
PDGF ELISA Kit |
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TGF-β antibody |
TGF-β recombinant protein |
TGF-β ELISA Kit |
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8-OHdG antibody |
8-OHdG recombinant protein |
8-OHdG ELISA Kit |
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caspase-3 antibody |
caspase-3 recombinant protein |
caspase-3 ELISA Kit |
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Bax antibody |
Bax recombinant protein |
Bax ELISA Kit |
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p53 antibody |
p53 recombinant protein |
p53 ELISA Kit |
REFERENCES
[1]Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics, PMID: 38695952.
[2]IL-23R is a senescence-linked circulating and tissue biomarker of aging, PMID: 39658621.