Cellular Aging Characteristics and Their Association with Age-Related Disorders
Abstract
:1. Introduction
2. Characteristics of the Senescent Phenotype
2.1. Genome Maintenance and Epigenetic Mechanisms
2.2. RNA Maintenance and Protein Synthesis
3. Mitochondria
4. Metabolic Activity
5. Interorganellar Communication
6. Proteostasis
7. Protein Carbonylation as an Aging Biomarker
8. Conclusions and Further Perspectives
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ROS | reactive oxygen species |
DSB | DNA double-strand break |
HR | homologous recombination |
NHEJ | nonhomologous end-joining |
EDARADD | Edar-associated death domain |
TOM1L1 | Target of Myb1-like 1 membrane |
NPTX2 | Neuronal pentraxin II |
HAT/KAT | histone/lysine acetyltransferase |
HDAC | histone deacetylase |
mTOR | target of rapamycin kinase |
PI3K | phosphoinositide 3-kinase |
AKT | protein kinase B |
UPS | ubiquitin–proteasome system |
CMA | chaperone-mediated autophagy |
DNP | 2,4-dinitrophenyl |
DNPH | 2,4-dinitrophenylhydrazine |
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Signaling Pathway | Mechanism | Role in Senescence Context | Ref. |
---|---|---|---|
Genome surveillance signaling | DNA repair | Normal lifespan control Mutations in the number of DNA repair genes caused premature aging. | [93] |
Telomere length-maintaining | Replicative lifespan control Dysfunctions were observed in telomere-mediated syndromes, such as dyskeratosis congenital, idiopathic pulmonary fibrosis, and Alzheimer’s disease. | [31,32,33,94] | |
Tumor-suppressor expressions | Promotion of longevity through cancer prevention Splicing defects of the p53 gene occurred in progeria, vascular aging, and Alzheimer’s disease. | [53] | |
Mitochondria and ROS signaling | Electron transport | Cellular energy control, reactive oxygen species (ROS) production/detoxification, and apoptosis A reduction of energy and ROS production could extend lifespans while reducing oxidative stress and the formation of carbonylated proteins. | [95] |
Sirtuin deacetylase activity | Regulation of replicative lifespan In neurodegenerative diseases, sirtuin expression increased, and they acted as neuroprotective molecules in sensing and mitigating ROS. Sirtuin proteins could promote or suppress cancer development. | [78,96,97] | |
Hormonal signaling | Insulin/IGF-1 activity | Growth, remodeling, and aging of tissues The insulin-like growth factor (IGF) system could play an important role in life processes (cell growth, division, differentiation, apoptosis, aging, and others) by binding with the receptor or activating multiple intracellular signaling cascades. Deregulation of the IGF-1 mechanism was associated with progeria, vascular aging, and Alzheimer’s disease. | [53,98] |
Transforming growth factor (TGF)-β action | Cell growth and proliferation, migration, the regulation of the inflammatory response, wound healing, fibrosis, and cellular apoptosis Impairment of the TGF-β1 signaling pathway was demonstrated to be specific for brain cells in Alzheimer’s patients, fibrosis, and various types of human cancer, including breast, colon, and renal cancer. | [99,100] | |
Metabolic signaling | Notch action | Embryogenesis, maintenance of tissue specific homeostasis, and stem cell differentiation The Notch pathway controlled proliferation, migration, the functions of tissue cells, as well as cross-talk between inflammatory cells and the innate immune system. Notch mutations were associated with sporadic Alzheimer’s disease and other neurodegenerative diseases such as Down syndrome, Pick’s and Prion’s disease, and CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy). | [101,102,103] |
Wnt action | Embryogenesis, cell fate determination, and cell survival Increased Wnt levels inhibited myogenic differentiation in the elderly. Impaired Notch-TGF-β–Wnt balances in stem cells resulted in the loss of cellular homeostasis. | [104,105] | |
Phosphoinositide 3-kinase (PI3K)/dependent-protein kinase B (AKT)/mTORC2 (PI3K/AKT/mTORC2) cascade | Cell proliferation, the regulation of translation, the quality control of proteins, and autophagy The regulation of pro- and antiaging signaling. The dysregulation of the PI3K–AKT–mTORC2 pathway was strongly associated with tumorigenesis. | [106,107] | |
Serine/threonine-protein kinase (Raf)/ Mitogen-activated protein kinases (MAPK/ERK) cascade | Regulation of apoptosis, cell survival, motility, adhesion, proliferation This pathway has a role in delivering extracellular signals to the nucleus, regulating cellular behavior and longevity. | [108,109,110] | |
Ras/cAMP-dependent protein kinase cascade | Regulation of cell survival, replicative senescence, autophagy, and cytoskeleton organization This cascade regulates caloric restriction and chronological lifespan in yeast. Mutations in Ras resulted in its activation occurring in 1/3 of human tumors (e.g., melanoma, thyroid, colon, and ovarian cancers). | [22,109] |
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Rudzińska, M.; Parodi, A.; Balakireva, A.V.; Chepikova, O.E.; Venanzi, F.M.; Zamyatnin, A.A., Jr. Cellular Aging Characteristics and Their Association with Age-Related Disorders. Antioxidants 2020, 9, 94. https://doi.org/10.3390/antiox9020094
Rudzińska M, Parodi A, Balakireva AV, Chepikova OE, Venanzi FM, Zamyatnin AA Jr. Cellular Aging Characteristics and Their Association with Age-Related Disorders. Antioxidants. 2020; 9(2):94. https://doi.org/10.3390/antiox9020094
Chicago/Turabian StyleRudzińska, Magdalena, Alessandro Parodi, Anastasia V. Balakireva, Olga E. Chepikova, Franco M. Venanzi, and Andrey A. Zamyatnin, Jr. 2020. "Cellular Aging Characteristics and Their Association with Age-Related Disorders" Antioxidants 9, no. 2: 94. https://doi.org/10.3390/antiox9020094
APA StyleRudzińska, M., Parodi, A., Balakireva, A. V., Chepikova, O. E., Venanzi, F. M., & Zamyatnin, A. A., Jr. (2020). Cellular Aging Characteristics and Their Association with Age-Related Disorders. Antioxidants, 9(2), 94. https://doi.org/10.3390/antiox9020094