Non-Genomic Hallmarks of Aging-The Review
Language English Country Switzerland Media electronic
Document type Journal Article, Review
Grant support
NU23J-07-00018
Ministry of Health
PubMed
37895144
PubMed Central
PMC10607657
DOI
10.3390/ijms242015468
PII: ijms242015468
Knihovny.cz E-resources
- Keywords
- aging, cancer, hallmarks, non-genomic,
- MeSH
- Humans MeSH
- Cell Communication MeSH
- Neoplasms * MeSH
- Cellular Senescence genetics MeSH
- Aging * metabolism MeSH
- Telomere Shortening MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Aging is a natural, gradual, and inevitable process associated with a series of changes at the molecular, cellular, and tissue levels that can lead to an increased risk of many diseases, including cancer. The most significant changes at the genomic level (DNA damage, telomere shortening, epigenetic changes) and non-genomic changes are referred to as hallmarks of aging. The hallmarks of aging and cancer are intertwined. Many studies have focused on genomic hallmarks, but non-genomic hallmarks are also important and may additionally cause genomic damage and increase the expression of genomic hallmarks. Understanding the non-genomic hallmarks of aging and cancer, and how they are intertwined, may lead to the development of approaches that could influence these hallmarks and thus function not only to slow aging but also to prevent cancer. In this review, we focus on non-genomic changes. We discuss cell senescence, disruption of proteostasis, deregualation of nutrient sensing, dysregulation of immune system function, intercellular communication, mitochondrial dysfunction, stem cell exhaustion and dysbiosis.
See more in PubMed
United Nations Department of Economic and Social Affairs . World Social Report 2023: Leaving No One Behind in an Ageing World. United Nations Department of Economic and Social Affairs; New York, NY, USA: 2023. World Social Report.
Ganguly P., Toghill B., Pathak S. Aging, Bone Marrow and Next-Generation Sequencing (NGS): Recent Advances and Future Perspectives. Int. J. Mol. Sci. 2021;22:12225. doi: 10.3390/ijms222212225. PubMed DOI PMC
Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. PubMed DOI
López-Otín C., Blasco M.A., Partridge L., Serrano M., Kroemer G. Hallmarks of Aging: An Expanding Universe. Cell. 2023;186:243–278. doi: 10.1016/j.cell.2022.11.001. PubMed DOI
Hanahan D., Weinberg R.A. The Hallmarks of Cancer. Cell. 2000;100:57–70. doi: 10.1016/S0092-8674(00)81683-9. PubMed DOI
Hanahan D., Weinberg R.A. Hallmarks of Cancer: The next Generation. Cell. 2011;144:646–674. doi: 10.1016/j.cell.2011.02.013. PubMed DOI
Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022;12:31–46. doi: 10.1158/2159-8290.CD-21-1059. PubMed DOI
Garber J.E., Offit K. Hereditary Cancer Predisposition Syndromes. J. Clin. Oncol. 2005;23:276–292. doi: 10.1200/JCO.2005.10.042. PubMed DOI
Campisi J. Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors. Cell. 2005;120:513–522. doi: 10.1016/j.cell.2005.02.003. PubMed DOI
Mylonas A., O’Loghlen A. Cellular Senescence and Ageing: Mechanisms and Interventions. Front. Aging. 2022;3:866718. doi: 10.3389/fragi.2022.866718. PubMed DOI PMC
González-Gualda E., Baker A.G., Fruk L., Muñoz-Espín D. A Guide to Assessing Cellular Senescence in Vitro and in Vivo. FEBS J. 2021;288:56–80. doi: 10.1111/febs.15570. PubMed DOI
Ohtani N. The Roles and Mechanisms of Senescence-Associated Secretory Phenotype (SASP): Can It Be Controlled by Senolysis? Inflamm. Regen. 2022;42:11. doi: 10.1186/s41232-022-00197-8. PubMed DOI PMC
Di Micco R., Krizhanovsky V., Baker D., di Fagagna F.A. Cellular Senescence in Ageing: From Mechanisms to Therapeutic Opportunities. Nat. Rev. Mol. Cell Biol. 2021;22:75. doi: 10.1038/s41580-020-00314-w. PubMed DOI PMC
Pan Y., Gu Z., Lyu Y., Yang Y., Chung M., Pan X., Cai S. Link between senescence and cell fate: Senescence-associated secretory phenotype and its effects on Stem cell fate transition. Rejuvenation Research. 2022;25:160–172. doi: 10.1089/rej.2022.0021. PubMed DOI
Milanovic M., Fan D.N.Y., Belenki D., Däbritz J.H.M., Zhao Z., Yu Y., Dörr J.R., Dimitrova L., Lenze D., Monteiro Barbosa I.A., et al. Senescence-Associated Reprogramming Promotes Cancer Stemness. Nature. 2017;553:96–100. doi: 10.1038/nature25167. PubMed DOI
Eid R.A., Alaa Edeen M., Shedid E.M., Kamal A.S.S., Warda M.M., Mamdouh F., Khedr S.A., Soltan M.A., Jeon H.W., Zaki M.S.A., et al. Targeting Cancer Stem Cells as the Key Driver of Carcinogenesis and Therapeutic Resistance. Int. J. Mol. Sci. 2023;24:1786. doi: 10.3390/ijms24021786. PubMed DOI PMC
Ressler S., Bartkova J., Niederegger H., Bartek J., Scharffetter-Kochanek K., Jansen-Dürr P., Wlaschek M. P16INK4A Is a Robust in Vivo Biomarker of Cellular Aging in Human Skin. Aging Cell. 2006;5:379–389. doi: 10.1111/j.1474-9726.2006.00231.x. PubMed DOI
Waaijer M.E.C., Parish W.E., Strongitharm B.H., van Heemst D., Slagboom P.E., de Craen A.J.M., Sedivy J.M., Westendorp R.G.J., Gunn D.A., Maier A.B. The Number of P16INK4a Positive Cells in Human Skin Reflects Biological Age. Aging Cell. 2012;11:722–725. doi: 10.1111/j.1474-9726.2012.00837.x. PubMed DOI PMC
Jiang D., de Vries J.C., Muschhammer J., Schatz S., Ye H., Hein T., Fidan M., Romanov V.S., Rinkevich Y., Scharffetter-Kochanek K. Local and Transient Inhibition of P21 Expression Ameliorates Age-Related Delayed Wound Healing. Wound Repair. Regen. 2020;28:49–60. doi: 10.1111/wrr.12763. PubMed DOI
Idda M.L., Mcclusky W.G., Lodde V., Munk R., Abdelmohsen K., Rossi M., Gorospe M. Survey of Senescent Cell Markers with Age in Human Tissues. Aging. 2020;12:4052–4066. doi: 10.18632/aging.102903. PubMed DOI PMC
Wicher S.A., Roos B.B., Teske J.J., Fang Y.H., Pabelick C., Prakash Y.S. Aging Increases Senescence, Calcium Signaling, and Extracellular Matrix Deposition in Human Airway Smooth Muscle. PLoS ONE. 2021;16:e0254710. doi: 10.1371/journal.pone.0254710. PubMed DOI PMC
Wyld L., Bellantuono I., Tchkonia T., Morgan J., Turner O., Foss F., George J., Danson S., Kirkland J.L. Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies. Cancers. 2020;12:2134. doi: 10.3390/cancers12082134. PubMed DOI PMC
Schmitt C.A., Wang B., Demaria M. Senescence and Cancer–Role and Therapeutic Opportunities. Nat. Rev. Clin. Oncol. 2022;19:619–636. doi: 10.1038/s41571-022-00668-4. PubMed DOI PMC
Azazmeh N., Assouline B., Winter E., Ruppo S., Nevo Y., Maly A., Meir K., Witkiewicz A.K., Cohen J., Rizou S.V., et al. Chronic Expression of P16INK4a in the Epidermis Induces Wnt-Mediated Hyperplasia and Promotes Tumor Initiation. Nat. Commun. 2020;11:2711. doi: 10.1038/s41467-020-16475-3. PubMed DOI PMC
Shen J., Song R., Fuemmeler B.F., McGuire K.P., Chow W.H., Zhao H. Biological Aging Marker P16INK4a in T Cells and Breast Cancer Risk. Cancers. 2020;12:3122. doi: 10.3390/cancers12113122. PubMed DOI PMC
Tsiambas E., Riziotis C., Mastronikolis N.S., Peschos D., Mortakis A., Kyroysis G., Mastronikolis S.N., Batistatou A., Lazaris A.C., Patsouris E., et al. Comparative P16IKN4A Expression in Laryngeal Carcinoma and Cervical Cancer Precursors: A Real-Time Grid-Based Immunocytochemistry Analysis. Anticancer Res. 2018;38:5805–5810. doi: 10.21873/anticanres.12920. PubMed DOI
Taniguchi T., Chikatsu N., Takahashi S., Fujita A., Uchimaru K., Asano S., Fujita T., Motokura T. Expression of P16INK4A and P14ARF in Hematological Malignancies. Leukemia. 1999;13:1760–1769. doi: 10.1038/sj.leu.2401557. PubMed DOI
Abdul-Aziz A.M., Sun Y., Hellmich C., Marlein C.R., Mistry J., Forde E., Piddock R.E., Shafat M.S., Morfakis A., Mehta T., et al. Acute Myeloid Leukemia Induces Protumoral P16INK4a-Driven Senescence in the Bone Marrow Microenvironment. Blood. 2019;133:446–456. doi: 10.1182/blood-2018-04-845420. PubMed DOI PMC
Huang Y., Wang W., Chen Y., Huang Y., Zhang J., He S., Tan Y., Qiang F., Li A., Røe O.D., et al. The Opposite Prognostic Significance of Nuclear and Cytoplasmic P21 Expression in Resectable Gastric Cancer Patients. J. Gastroenterol. 2014;49:1441–1452. doi: 10.1007/s00535-013-0900-4. PubMed DOI
Santra M., Dill K.A., De Graff A.M.R. Proteostasis Collapse Is a Driver of Cell Aging and Death. Proc. Natl. Acad. Sci. USA. 2019;116:22173–22178. doi: 10.1073/pnas.1906592116. PubMed DOI PMC
Stegeman R., Weake V.M. Transcriptional Signatures of Aging. J. Mol. Biol. 2017;429:2427–2437. doi: 10.1016/j.jmb.2017.06.019. PubMed DOI PMC
Kim H.S., Pickering A.M. Protein Translation Paradox: Implications in Translational Regulation of Aging. Front. Cell Dev. Biol. 2023;11:1129281. doi: 10.3389/fcell.2023.1129281. PubMed DOI PMC
Wang M., Kaufman R.J. Protein Misfolding in the Endoplasmic Reticulum as a Conduit to Human Disease. Nature. 2016;529:326–335. doi: 10.1038/nature17041. PubMed DOI
Frankowska N., Lisowska K., Witkowski J.M. Proteolysis Dysfunction in the Process of Aging and Age-Related Diseases. Front. Aging. 2022;3:85. doi: 10.3389/fragi.2022.927630. PubMed DOI PMC
Sacramento E.K., Kirkpatrick J.M., Mazzetto M., Baumgart M., Bartolome A., Sanzo S., Di Caterino C., Sanguanini M., Papaevgeniou N., Lefaki M., et al. Reduced Proteasome Activity in the Aging Brain Results in Ribosome Stoichiometry Loss and Aggregation. Mol. Syst. Biol. 2020;16:e9596. doi: 10.15252/msb.20209596. PubMed DOI PMC
Pomatto L.C.D., Wong S., Carney C., Shen B., Tower J., Davies K.J.A. The Age- and Sex-Specific Decline of the 20s Proteasome and the Nrf2/CncC Signal Transduction Pathway in Adaption and Resistance to Oxidative Stress in Drosophila melanogaster. Aging. 2017;9:1153–1185. doi: 10.18632/aging.101218. PubMed DOI PMC
Wodrich A.P.K., Scott A.W., Shukla A.K., Harris B.T., Giniger E. The Unfolded Protein Responses in Health, Aging, and Neurodegeneration: Recent Advances and Future Considerations. Front. Mol. Neurosci. 2022;15:831116. doi: 10.3389/fnmol.2022.831116. PubMed DOI PMC
Morozov A.V., Karpov V.L. Proteasomes and Several Aspects of Their Heterogeneity Relevant to Cancer. Front. Oncol. 2019;9:761. doi: 10.3389/fonc.2019.00761. PubMed DOI PMC
Madden E., Logue S.E., Healy S.J., Manie S., Samali A. The Role of the Unfolded Protein Response in Cancer Progression: From Oncogenesis to Chemoresistance. Biol. Cell. 2019;111:1–17. doi: 10.1111/boc.201800050. PubMed DOI
Parzych K.R., Klionsky D.J. An Overview of Autophagy: Morphology, Mechanism, and Regulation. Antioxid. Redox Signal. 2014;20:460–473. doi: 10.1089/ars.2013.5371. PubMed DOI PMC
Hollenstein D.M., Kraft C. Autophagosomes Are Formed at a Distinct Cellular Structure. Curr. Opin. Cell Biol. 2020;65:50–57. doi: 10.1016/j.ceb.2020.02.012. PubMed DOI PMC
Xu F., Tautenhahn H.M., Dirsch O., Dahmen U. Modulation of Autophagy: A Novel “Rejuvenation” Strategy for the Aging Liver. Oxid. Med. Cell Longev. 2021;2021:6611126. doi: 10.1155/2021/6611126. PubMed DOI PMC
Yang N., Liu X., Niu X., Wang X., Jiang R., Yuan N., Wang J., Zhang C., Lim K.L., Lu L. Activation of Autophagy Ameliorates Age-Related Neurogenesis Decline and Neurodysfunction in Adult Mice. Stem Cell Rev. Rep. 2022;18:626–641. doi: 10.1007/s12015-021-10265-0. PubMed DOI
Ko S.H., Apple E.C., Liu Z., Chen L. Age-Dependent Autophagy Induction after Injury Promotes Axon Regeneration by Limiting NOTCH. Autophagy. 2020;16:2052–2068. doi: 10.1080/15548627.2020.1713645. PubMed DOI PMC
Orhon I., Rocchi C., Villarejo-Zori B., Serrano Martinez P., Baanstra M., Brouwer U., Boya P., Coppes R., Reggiori F. Autophagy Induction during Stem Cell Activation Plays a Key Role in Salivary Gland Self-Renewal. Autophagy. 2022;18:293–308. doi: 10.1080/15548627.2021.1924036. PubMed DOI PMC
Chen W., Chen Y., Liu Y., Wang X. Autophagy in Muscle Regeneration: Potential Therapies for Myopathies. J. Cachexia Sarcopenia Muscle. 2022;13:1673–1685. doi: 10.1002/jcsm.13000. PubMed DOI PMC
Xie F., Xu S., Lu Y., Wong K.F., Sun L., Hasan K.M.M., Ma A.C.H., Tse G., Manno S.H.C., Tian L., et al. Metformin Accelerates Zebrafish Heart Regeneration by Inducing Autophagy. NPJ Regen. Med. 2021;6:62. doi: 10.1038/s41536-021-00172-w. PubMed DOI PMC
Versaci F., Valenti V., Forte M., Cammisotto V., Nocella C., Bartimoccia S., Schirone L., Schiavon S., Vecchio D., D’ambrosio L., et al. Aging-Related Decline of Autophagy in Patients with Atrial Fibrillation—A Post Hoc Analysis of the ATHERO-AF Study. Antioxidants. 2022;11:698. doi: 10.3390/antiox11040698. PubMed DOI PMC
Huang J., Xu J., Pang S., Bai B., Yan B. Age-Related Decrease of the LAMP-2 Gene Expression in Human Leukocytes. Clin. Biochem. 2012;45:1229–1232. doi: 10.1016/j.clinbiochem.2012.06.016. PubMed DOI
Towers C.G., Thorburn A. Therapeutic Targeting of Autophagy. EBioMedicine. 2016;14:15. doi: 10.1016/j.ebiom.2016.10.034. PubMed DOI PMC
Mulcahy Levy J.M., Thorburn A. Autophagy in Cancer: Moving from Understanding Mechanism to Improving Therapy Responses in Patients. Cell Death Differ. 2020;27:843–857. doi: 10.1038/s41418-019-0474-7. PubMed DOI PMC
Chavez-Dominguez R., Perez-Medina M., Lopez-Gonzalez J.S., Galicia-Velasco M., Aguilar-Cazares D. The Double-Edge Sword of Autophagy in Cancer: From Tumor Suppression to Pro-Tumor Activity. Front. Oncol. 2020;10:578418. doi: 10.3389/fonc.2020.578418. PubMed DOI PMC
Schläfli A.M., Adams O., Galván J.A., Gugger M., Savic S., Bubendorf L., Schmid R.A., Becker K.F., Tschan M.P., Langer R., et al. Prognostic Value of the Autophagy Markers LC3 and P62/SQSTM1 in Early-Stage Non-Small Cell Lung Cancer. Oncotarget. 2016;7:39544–39555. doi: 10.18632/oncotarget.9647. PubMed DOI PMC
Deng D., Luo K., Liu H., Nie X., Xue L., Wang R., Xu Y., Cui J., Shao N., Zhi F. P62 Acts as an Oncogene and Is Targeted by MiR-124-3p in Glioma. Cancer Cell Int. 2019;19:280. doi: 10.1186/s12935-019-1004-x. PubMed DOI PMC
Masuda G., Yashiro M., Kitayama K., Miki Y., Kasashima H., Kinoshita H., Morisaki T., Fukuoka T., Hasegawa T., Sakurai K., et al. Clinicopathological Correlations of Autophagy-Related Proteins LC3, Beclin 1 and P62 in Gastric Cancer. Anticancer Res. 2016;36:129–136. PubMed
Mohamadimaram M., Farsani M.A., Mirzaeian A., Shahsavan S., Hajifathali A., Parkhihdeh S., Mohammadi M.H. Evaluation of ATG7 and Light Chain 3 (LC3) Autophagy Genes Expression in AML Patients. Iran. J. Pharm. Res. 2019;18:1060–1066. doi: 10.22037/IJPR.2019.1100682. PubMed DOI PMC
Twarda-clapa A., Olczak A., Białkowska A.M., Koziołkiewicz M. Advanced Glycation End-Products (AGEs): Formation, Chemistry, Classification, Receptors, and Diseases Related to AGEs. Cells. 2022;11:1312. doi: 10.3390/cells11081312. PubMed DOI PMC
Poulsen M.W., Hedegaard R.V., Andersen J.M., de Courten B., Bügel S., Nielsen J., Skibsted L.H., Dragsted L.O. Advanced Glycation Endproducts in Food and Their Effects on Health. Food Chem. Toxicol. 2013;60:10–37. doi: 10.1016/j.fct.2013.06.052. PubMed DOI
Aragonès G., Rowan S., Francisco S.G., Whitcomb E.A., Yang W., Perini-Villanueva G., Schalkwijk C.G., Taylor A., Bejarano E. The Glyoxalase System in Age-Related Diseases: Nutritional Intervention as Anti-Ageing Strategy. Cells. 2021;10:1852. doi: 10.3390/cells10081852. PubMed DOI PMC
Patel S.H., Yue F., Saw S.K., Foguth R., Cannon J.R., Shannahan J.H., Kuang S., Sabbaghi A., Carroll C.C. Advanced Glycation End-Products Suppress Mitochondrial Function and Proliferative Capacity of Achilles Tendon-Derived Fibroblasts. Sci. Rep. 2019;9:12614. doi: 10.1038/s41598-019-49062-8. PubMed DOI PMC
Rungratanawanich W., Qu Y., Wang X., Essa M.M., Song B.J. Advanced Glycation End Products (AGEs) and Other Adducts in Aging-Related Diseases and Alcohol-Mediated Tissue Injury. Exp. Mol. Med. 2021;53:168–188. doi: 10.1038/s12276-021-00561-7. PubMed DOI PMC
Davis K.E., Prasad C., Vijayagopal P., Juma S., Imrhan V. Advanced Glycation End Products, Inflammation, and Chronic Metabolic Diseases: Links in a Chain? Crit. Rev. Food Sci. Nutr. 2016;56:989–998. doi: 10.1080/10408398.2012.744738. PubMed DOI
Wei B., Berning K., Quan C., Zhang Y.T. Glycation of Antibodies: Modification, Methods and Potential Effects on Biological Functions. mAbs. 2017;9:586. doi: 10.1080/19420862.2017.1300214. PubMed DOI PMC
He Y., Zhou C., Huang M., Tang C., Liu X., Yue Y., Diao Q., Zheng Z., Liu D. Glyoxalase System: A Systematic Review of Its Biological Activity, Related-Diseases, Screening Methods and Small Molecule Regulators. Biomed. Pharmacother. 2020;131:110663. doi: 10.1016/j.biopha.2020.110663. PubMed DOI
Farrera D.O., Galligan J.J. The Human Glyoxalase Gene Family in Health and Disease. Chem. Res. Toxicol. 2022;35:1766–1776. doi: 10.1021/acs.chemrestox.2c00182. PubMed DOI PMC
Chaudhuri J., Bains Y., Guha S., Kahn A., Hall D., Bose N., Gugliucci A., Kapahi P. The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality. Cell Metab. 2018;28:337–352. doi: 10.1016/j.cmet.2018.08.014. PubMed DOI PMC
Azizian-Farsani F., Abedpoor N., Hasan Sheikhha M., Gure A.O., Nasr-Esfahani M.H., Ghaedi K. Receptor for Advanced Glycation End Products Acts as a Fuel to Colorectal Cancer Development. Front. Oncol. 2020;10:552283. doi: 10.3389/fonc.2020.552283. PubMed DOI PMC
Schröter D., Höhn A. Role of Advanced Glycation End Products in Carcinogenesis and Their Therapeutic Implications. Curr. Pharm. Des. 2019;24:261. doi: 10.2174/1381612825666190130145549. PubMed DOI PMC
Peng Y., Liu F., Qiao Y., Wang P., Du H., Si C., Wang X., Chen K., Song F. Genetically Modified Circulating Levels of Advanced Glycation End-Products and Their Soluble Receptor (AGEs-RAGE Axis) with Risk and Mortality of Breast Cancer. Cancers. 2022;14:6124. doi: 10.3390/cancers14246124. PubMed DOI PMC
Efeyan A., Comb W.C., Sabatini D.M. Nutrient-Sensing Mechanisms and Pathways. Nature. 2015;517:302–310. doi: 10.1038/nature14190. PubMed DOI PMC
Lee H., Lee S.J.V. Recent Progress in Regulation of Aging by Insulin/IGF-1 Signaling in Caenorhabditis Elegans. Mol. Cells. 2022;45:763. doi: 10.14348/molcells.2022.0097. PubMed DOI PMC
Altintas O., Park S., Lee S.J.V. The Role of Insulin/IGF-1 Signaling in the Longevity of Model Invertebrates, C. Elegans and D. Melanogaster. BMB Rep. 2016;49:81–92. doi: 10.5483/BMBRep.2016.49.2.261. PubMed DOI PMC
Vitale G., Pellegrino G., Vollery M., Hofland L.J. Role of IGF-1 System in the Modulation of Longevity: Controversies and New Insights from a Centenarians’ Perspective. Front. Endocrinol. 2019;10:27. doi: 10.3389/fendo.2019.00027. PubMed DOI PMC
Friedrich N., Thuesen B., Jrøgensen T., Juul A., Spielhagen C., Wallaschofksi H., Linneberg A. The Association Between IGF-I and Insulin ResistanceA General Population Study in Danish Adults. Diabetes Care. 2012;35:768–773. doi: 10.2337/dc11-1833. PubMed DOI PMC
Zhu H., Xu Y., Gong F., Shan G., Yang H., Xu K., Zhang D., Cheng X., Zhang Z., Chen S., et al. Reference Ranges for Serum Insulin-like Growth Factor I (IGF-I) in Healthy Chinese Adults. PLoS ONE. 2017;12:e0185561. doi: 10.1371/journal.pone.0185561. PubMed DOI PMC
Vitale G., Barbieri M., Kamenetskaya M., Paolisso G. GH/IGF-I/Insulin System in Centenarians. Mech. Ageing Dev. 2017;165:107–114. doi: 10.1016/j.mad.2016.12.001. PubMed DOI
Milman S., Atzmon G., Huffman D.M., Wan J., Crandall J.P., Cohen P., Barzilai N. Low Insulin-like Growth Factor-1 Level Predicts Survival in Humans with Exceptional Longevity. Aging Cell. 2014;13:769–771. doi: 10.1111/acel.12213. PubMed DOI PMC
Paolisso G., Ammendola S., Del Buono A., Gambardella A., Riondino M., Tagliamonte M.R., Rizzo M.R., Carella C., Varricchio M. Serum Levels of Insulin-Like Growth Factor-I (IGF-I) and IGF-Binding Protein-3 in Healthy Centenarians: Relationship with Plasma Leptin and Lipid Concentrations, Insulin Action, and Cognitive Function. J. Clin. Endocrinol. Metab. 1997;82:2204–2209. doi: 10.1210/jcem.82.7.4087. PubMed DOI
Vitale G., Brugts M.P., Ogliari G., Castaldi D., Fatti L.M., Varewijck A.J., Lamberts S.W., Monti D., Bucci L., Cevenini E., et al. Low Circulating IGF-I Bioactivity Is Associated with Human Longevity: Findings in Centenarians’ Offspring. Aging. 2012;4:580–589. doi: 10.18632/aging.100484. PubMed DOI PMC
Micó V., Berninches L., Tapia J., Daimiel L. NutrimiRAging: Micromanaging Nutrient Sensing Pathways through Nutrition to Promote Healthy Aging. Int. J. Mol. Sci. 2017;18:915. doi: 10.3390/ijms18050915. PubMed DOI PMC
Papadopoli D., Boulay K., Kazak L., Pollak M., Mallette F.A., Topisirovic I., Hulea L. MTOR as a Central Regulator of Lifespan and Aging. F1000Research. 2019;8:998. doi: 10.12688/f1000research.17196.1. PubMed DOI PMC
Wang N., Luo Z., Jin M., Sheng W., Wang H.T., Long X., Wu Y., Hu P., Xu H., Zhang X. Exploration of Age-Related Mitochondrial Dysfunction and the Anti-Aging Effects of Resveratrol in Zebrafish Retina. Aging. 2019;11:3117–3137. doi: 10.18632/aging.101966. PubMed DOI PMC
Zhang Y., Zhang J., Wang S. The Role of Rapamycin in Healthspan Extension via the Delay of Organ Aging. Ageing Res. Rev. 2021;70:101376. doi: 10.1016/j.arr.2021.101376. PubMed DOI
Kawakami Y., Hambright W.S., Takayama K., Mu X., Lu A., Cummins J.H., Matsumoto T., Yurube T., Kuroda R., Kurosaka M., et al. Rapamycin Rescues Age-Related Changes in Muscle-Derived Stem/Progenitor Cells from Progeroid Mice. Mol. Ther. Methods Clin. Dev. 2019;14:64–76. doi: 10.1016/j.omtm.2019.05.011. PubMed DOI PMC
Salminen A., Kaarniranta K., Kauppinen A. Insulin/IGF-1 Signaling Promotes Immunosuppression via the STAT3 Pathway: Impact on the Aging Process and Age-Related Diseases. Inflamm. Res. 2021;70:1043–1061. doi: 10.1007/s00011-021-01498-3. PubMed DOI PMC
Murphy N., Carreras-Torres R., Song M., Chan A.T., Martin R.M., Papadimitriou N., Dimou N., Tsilidis K.K., Banbury B., Bradbury K.E., et al. Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate with Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses. Gastroenterology. 2020;158:1300–1312.e20. doi: 10.1053/j.gastro.2019.12.020. PubMed DOI PMC
Stancu A.L. AMPK Activation Can Delay Aging. Discoveries. 2015;3:e53. doi: 10.15190/d.2015.45. PubMed DOI PMC
Ameen O., Samaka R.M., Abo-Elsoud R.A.A. Metformin Alleviates Neurocognitive Impairment in Aging via Activation of AMPK/BDNF/PI3K Pathway. Sci. Rep. 2022;12:17084. doi: 10.1038/s41598-022-20945-7. PubMed DOI PMC
Xu W., Luo Y., Yin J., Huang M., Luo F. Targeting AMPK Signaling by Polyphenols: A Novel Strategy for Tackling Aging. Food Funct. 2023;14:56–73. doi: 10.1039/D2FO02688K. PubMed DOI
Campos J.C., Marchesi Bozi L.H., Krum B., Grassmann Bechara L.R., Ferreira N.D., Arini G.S., Albuquerque R.P., Traa A., Ogawa T., van der Bliek A.M., et al. Exercise Preserves Physical Fitness during Aging through AMPK and Mitochondrial Dynamics. Proc. Natl. Acad. Sci. USA. 2023;120:e2204750120. doi: 10.1073/pnas.2204750120. PubMed DOI PMC
Chen H., Liu X., Zhu W., Chen H., Hu X., Jiang Z., Xu Y., Wang L., Zhou Y., Chen P., et al. SIRT1 Ameliorates Age-Related Senescence of Mesenchymal Stem Cells via Modulating Telomere Shelterin. Front. Aging Neurosci. 2014;6:103. doi: 10.3389/fnagi.2014.00103. PubMed DOI PMC
Di Emidio G., Falone S., Vitti M., D’Alessandro A.M., Vento M., Di Pietro C., Amicarelli F., Tatone C. SIRT1 Signalling Protects Mouse Oocytes against Oxidative Stress and Is Deregulated during Aging. Hum. Reprod. 2014;29:2006–2017. doi: 10.1093/humrep/deu160. PubMed DOI
Wang C., Wang F., Li Z., Huang L., Cao Q., Chen S. MeCP2 Mediated Dysfunction in Senescent EPCs. Oncotarget. 2017;8:78289–78299. doi: 10.18632/oncotarget.20961. PubMed DOI PMC
Chen C., Zhou M., Ge Y., Wang X. SIRT1 and Aging Related Signaling Pathways. Mech. Ageing Dev. 2020;187:111215. doi: 10.1016/j.mad.2020.111215. PubMed DOI
Kilic U., Gok O., Erenberk U., Dundaroz M.R., Torun E., Kucukardali Y., Elibol-Can B., Uysal O., Dundar T. A Remarkable Age-Related Increase in SIRT1 Protein Expression against Oxidative Stress in Elderly: SIRT1 Gene Variants and Longevity in Human. PLoS ONE. 2015;10:e0117954. doi: 10.1371/journal.pone.0117954. PubMed DOI PMC
de Arellano M.L.B., Pozdniakova S., Kühl A.A., Baczko I., Ladilov Y., Regitz-Zagrosek V. Sex Differences in the Aging Human Heart: Decreased Sirtuins, pro-Inflammatory Shift and Reduced Anti-Oxidative Defense. Aging. 2019;11:1918. doi: 10.18632/aging.101881. PubMed DOI PMC
Vara-Ciruelos D., Russell F.M., Grahame Hardie D. The Strange Case of AMPK and Cancer: Dr Jekyll or Mr Hyde? Open Biol. 2019;9:190099. doi: 10.1098/rsob.190099. PubMed DOI PMC
Hsu C.C., Peng D., Cai Z., Lin H.K. AMPK Signaling and Its Targeting in Cancer Progression and Treatment. Semin. Cancer Biol. 2022;85:52–68. doi: 10.1016/j.semcancer.2021.04.006. PubMed DOI PMC
Edatt L., Poyyakkara A., Raji G.R., Ramachandran V., Shankar S.S., Kumar V.B.S. Role of Sirtuins in Tumor Angiogenesis. Front. Oncol. 2019;9:1516. doi: 10.3389/fonc.2019.01516. PubMed DOI PMC
Huang S., Li Y., Sheng G., Meng Q., Hu Q., Gao X., Shang Z., Lv Q. Sirtuin 1 Promotes Autophagy and Proliferation of Endometrial Cancer Cells by Reducing Acetylation Level of LC3. Cell Biol. Int. 2021;45:1050–1059. doi: 10.1002/cbin.11549. PubMed DOI
Carafa V., Altucci L., Nebbioso A. Dual Tumor Suppressor and Tumor Promoter Action of Sirtuins in Determining Malignant Phenotype. Front. Pharmacol. 2019;9:38. doi: 10.3389/fphar.2019.00038. PubMed DOI PMC
Dominiak A., Chełstowska B., Olejarz W., Nowicka G. Communication in the Cancer Microenvironment as a Target for Therapeutic Interventions. Cancers. 2020;12:1232. doi: 10.3390/cancers12051232. PubMed DOI PMC
Ribeiro-Rodrigues T.M., Kelly G., Korolchuk V.I., Girao H. Intercellular Communication and Aging. Aging: Fundam. Biol. Soc. Impact. 2023:257–274. doi: 10.1016/B978-0-12-823761-8.00005-7. DOI
Fafián-Labora J.A., O’Loghlen A. Classical and Nonclassical Intercellular Communication in Senescence and Ageing. Trends Cell Biol. 2020;30:628–639. doi: 10.1016/j.tcb.2020.05.003. PubMed DOI
Brábek J., Jakubek M., Vellieux F., Novotný J., Kolář M., Lacina L., Szabo P., Strnadová K., Rösel D., Dvořánková B., et al. Interleukin-6: Molecule in the Intersection of Cancer, Ageing and COVID-19. Int. J. Mol. Sci. 2020;21:7937. doi: 10.3390/ijms21217937. PubMed DOI PMC
Ataie-Kachoie P., Pourgholami M.H., Morris D.L. Inhibition of the IL-6 Signaling Pathway: A Strategy to Combat Chronic Inflammatory Diseases and Cancer. Cytokine Growth Factor. Rev. 2013;24:163–173. doi: 10.1016/j.cytogfr.2012.09.001. PubMed DOI
Romero-García N., Huete-Acevedo J., Mas-Bargues C., Sanz-Ros J., Dromant M., Borrás C. The Double-Edged Role of Extracellular Vesicles in the Hallmarks of Aging. Biomolecules. 2023;13:165. doi: 10.3390/biom13010165. PubMed DOI PMC
Alberro A., Sáenz-Cuesta M., Muñoz-Culla M., Mateo-Abad M., Gonzalez E., Carrasco-Garcia E., Araúzo-Bravo M.J., Matheu A., Vergara I., Otaegui D. Inflammaging and Frailty Status Do Not Result in an Increased Extracellular Vesicle Concentration in Circulation. Int. J. Mol. Sci. 2016;17:1168. doi: 10.3390/ijms17071168. PubMed DOI PMC
Eitan E., Green J., Bodogai M., Mode N.A., Bæk R., Jørgensen M.M., Freeman D.W., Witwer K.W., Zonderman A.B., Biragyn A., et al. Age-Related Changes in Plasma Extracellular Vesicle Characteristics and Internalization by Leukocytes. Sci. Rep. 2017;7:1342. doi: 10.1038/s41598-017-01386-z. PubMed DOI PMC
Weilner S., Keider V., Winter M., Harreither E., Salzer B., Weiss F., Schraml E., Messner P., Pietschmann P., Hildner F., et al. Vesicular Galectin-3 Levels Decrease with Donor Age and Contribute to the Reduced Osteo-Inductive Potential of Human Plasma Derived Extracellular Vesicles. Aging. 2016;8:16–33. doi: 10.18632/aging.100865. PubMed DOI PMC
Zhang X., Hubal M.J., Kraus V.B. Immune Cell Extracellular Vesicles and Their Mitochondrial Content Decline with Ageing. Immun. Ageing. 2020;17:1. doi: 10.1186/s12979-019-0172-9. PubMed DOI PMC
Gomes De Andrade G., Reck Cechinel L., Bertoldi K., Galvão F., Valdeci Worm P., Rodrigues Siqueira I. The Aging Process Alters IL-1β and CD63 Levels Differently in Extracellular Vesicles Obtained from the Plasma and Cerebrospinal Fluid. Neuroimmunomodulation. 2018;25:18–22. doi: 10.1159/000488943. PubMed DOI
Goetzl E.J., Goetzl L., Karliner J.S., Tang N., Pulliam L. Human Plasma Platelet-Derived Exosomes: Effects of Aspirin. FASEB J. 2016;30:2058. doi: 10.1096/fj.201500150R. PubMed DOI PMC
Hamdan Y., Mazini L., Malka G. Exosomes and Micro-RNAs in Aging Process. Biomedicines. 2021;9:968. doi: 10.3390/biomedicines9080968. PubMed DOI PMC
Manni G., Buratta S., Pallotta M.T., Chiasserini D., Di Michele A., Emiliani C., Giovagnoli S., Pascucci L., Romani R., Bellezza I., et al. Extracellular Vesicles in Aging: An Emerging Hallmark? Cells. 2023;12:527. doi: 10.3390/cells12040527. PubMed DOI PMC
D’Anca M., Fenoglio C., Serpente M., Arosio B., Cesari M., Scarpini E.A., Galimberti D. Exosome Determinants of Physiological Aging and Age-Related Neurodegenerative Diseases. Front. Aging Neurosci. 2019;11:232. doi: 10.3389/fnagi.2019.00232. PubMed DOI PMC
Machida T., Tomofuji T., Ekuni D., Maruyama T., Yoneda T., Kawabata Y., Mizuno H., Miyai H., Kunitomo M., Morita M. MicroRNAs in Salivary Exosome as Potential Biomarkers of Aging. Int. J. Mol. Sci. 2015;16:21294–21309. doi: 10.3390/ijms160921294. PubMed DOI PMC
Mensà E., Guescini M., Giuliani A., Bacalini M.G., Ramini D., Corleone G., Ferracin M., Fulgenzi G., Graciotti L., Prattichizzo F., et al. Small Extracellular Vesicles Deliver MiR-21 and MiR-217 as pro-Senescence Effectors to Endothelial Cells. J. Extracell. Vesicles. 2020;9:1725285. doi: 10.1080/20013078.2020.1725285. PubMed DOI PMC
Leal A.C., Mizurini D.M., Gomes T., Rochael N.C., Saraiva E.M., Dias M.S., Werneck C.C., Sielski M.S., Vicente C.P., Monteiro R.Q. Tumor-Derived Exosomes Induce the Formation of Neutrophil Extracellular Traps: Implications for the Establishment of Cancer-Associated Thrombosis. Sci. Rep. 2017;7:6438. doi: 10.1038/s41598-017-06893-7. PubMed DOI PMC
Matsumoto Y., Kano M., Akutsu Y., Hanari N., Hoshino I., Murakami K., Usui A., Suito H., Takahashi M., Otsuka R., et al. Quantification of Plasma Exosome Is a Potential Prognostic Marker for Esophageal Squamous Cell Carcinoma. Oncol. Rep. 2016;36:2535–2543. doi: 10.3892/or.2016.5066. PubMed DOI PMC
Bamankar S., Londhe V.Y. The Rise of Extracellular Vesicles as New Age Biomarkers in Cancer Diagnosis: Promises and Pitfalls. Technol. Cancer Res. Treat. 2023;22:9266. doi: 10.1177/15330338221149266. PubMed DOI PMC
Grimolizzi F., Monaco F., Leoni F., Bracci M., Staffolani S., Bersaglieri C., Gaetani S., Valentino M., Amati M., Rubini C., et al. Exosomal MiR-126 as a Circulating Biomarker in Non-Small-Cell Lung Cancer Regulating Cancer Progression. Sci. Rep. 2017;7:15277. doi: 10.1038/s41598-017-15475-6. PubMed DOI PMC
Mihelich B.L., Dambal S., Lin S., Nonn L. MiR-182, of the MiR-183 Cluster Family, Is Packaged in Exosomes and Is Detected in Human Exosomes from Serum, Breast Cells and Prostate Cells. Oncol. Lett. 2016;12:1197–1203. doi: 10.3892/ol.2016.4710. PubMed DOI PMC
Zhao Q., Zheng X., Guo H., Xue X., Zhang Y., Niu M., Cui J., Liu H., Luo H., Yang D., et al. Serum Exosomal MiR-941 as a Promising Oncogenic Biomarker for Laryngeal Squamous Cell Carcinoma. J. Cancer. 2020;11:5329–5344. doi: 10.7150/jca.45394. PubMed DOI PMC
Liu W., Yang D., Chen L., Liu Q., Wang W., Yang Z., Shang A., Quan W., Li D. Plasma Exosomal MiRNA-139-3p Is a Novel Biomarker of Colorectal Cancer. J. Cancer. 2020;11:4899–4906. doi: 10.7150/jca.45548. PubMed DOI PMC
Lu R.J., Wang E.K., Benayoun B.A. Functional Genomics of Inflamm-Aging and Immunosenescence. Brief. Funct. Genom. 2022;21:43–55. doi: 10.1093/bfgp/elab009. PubMed DOI PMC
Haynes L. Aging of the Immune System: Research Challenges to Enhance the Health Span of Older Adults. Front. Aging. 2020;1:2. doi: 10.3389/fragi.2020.602108. PubMed DOI PMC
Mogilenko D.A., Shchukina I., Artyomov M.N. Immune Ageing at Single-Cell Resolution. Nat. Rev. Immunol. 2021;22:484–498. doi: 10.1038/s41577-021-00646-4. PubMed DOI PMC
Thomas R., Wang W., Su D.M. Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging. Immun. Ageing. 2020;17:2. doi: 10.1186/s12979-020-0173-8. PubMed DOI PMC
Mittelbrunn M., Kroemer G. Hallmarks of T Cell Aging. Nat. Immunol. 2021;22:687–698. doi: 10.1038/s41590-021-00927-z. PubMed DOI
Duggal N.A. Reversing the Immune Ageing Clock: Lifestyle Modifications and Pharmacological Interventions. Biogerontology. 2018;19:481–496. doi: 10.1007/s10522-018-9771-7. PubMed DOI PMC
Kurioka A., Klenerman P. Aging Unconventionally: Γδ T Cells, INKT Cells, and MAIT Cells in Aging. Semin. Immunol. 2023;69:101816. doi: 10.1016/j.smim.2023.101816. PubMed DOI
Ma S., Wang C., Mao X., Hao Y. R Cells Dysfunction Associated with Aging and Autoimmune Disease. Front. Immunol. 2019;10:318. doi: 10.3389/fimmu.2019.00318. PubMed DOI PMC
Mouat I.C., Goldberg E., Horwitz M.S. Age-Associated B Cells in Autoimmune Diseases. Cell. Mol. Life Sci. 2022;79:402. doi: 10.1007/s00018-022-04433-9. PubMed DOI PMC
Brauning A., Rae M., Zhu G., Fulton E., Admasu T.D., Stolzing A., Sharma A. Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions. Cells. 2022;11:1017. doi: 10.3390/cells11061017. PubMed DOI PMC
De Maeyer R.P.H., Chambers E.S. The Impact of Ageing on Monocytes and Macrophages. Immunol. Lett. 2021;230:1–10. doi: 10.1016/j.imlet.2020.12.003. PubMed DOI
Yoo H.J., Kwon M.S. Aged Microglia in Neurodegenerative Diseases: Microglia Lifespan and Culture Methods. Front. Aging Neurosci. 2022;13:928. doi: 10.3389/fnagi.2021.766267. PubMed DOI PMC
Hearps A.C., Martin G.E., Angelovich T.A., Cheng W.J., Maisa A., Landay A.L., Jaworowski A., Crowe S.M. Aging Is Associated with Chronic Innate Immune Activation and Dysregulation of Monocyte Phenotype and Function. Aging Cell. 2012;11:867–875. doi: 10.1111/j.1474-9726.2012.00851.x. PubMed DOI
Chougnet C.A., Thacker R.I., Shehata H.M., Hennies C.M., Lehn M.A., Lages C.S., Janssen E.M. Loss of Phagocytic and Antigen Cross-Presenting Capacity in Aging Dendritic Cells Is Associated with Mitochondrial Dysfunction. J. Immunol. 2015;195:2624–2632. doi: 10.4049/jimmunol.1501006. PubMed DOI PMC
Adrover J.M., Nicolás-Ávila J.A., Hidalgo A. Aging: A Temporal Dimension for Neutrophils. Trends Immunol. 2016;37:334–345. doi: 10.1016/j.it.2016.03.005. PubMed DOI
Bulut O., Kilic G., Dominguez-Andres J., Netea M.G. Overcoming Immune Dysfunction in the Elderly: Trained Immunity as a Novel Approach. Int. Immunol. 2020;32:741–753. doi: 10.1093/intimm/dxaa052. PubMed DOI PMC
Pilkington S.M., Barron M.J., Watson R.E.B., Griffiths C.E.M., Bulfone-Paus S. Aged Human Skin Accumulates Mast Cells with Altered Functionality That Localize to Macrophages and Vasoactive Intestinal Peptide-positive Nerve Fibres. Br. J. Dermatol. 2019;180:849. doi: 10.1111/bjd.17268. PubMed DOI PMC
Chatterjee V., Gashev A.A. Aging-Associated Shifts in Functional Status of Mast Cells Located by Adult and Aged Mesenteric Lymphatic Vessels. Am. J. Physiol. Heart Circ. Physiol. 2012;303:H693–H702. doi: 10.1152/ajpheart.00378.2012. PubMed DOI PMC
Van Beek A.A., Fransen F., Meijer B., De Vos P., Knol E.F., Savelkoul H.F.J. Aged Mice Display Altered Numbers and Phenotype of Basophils, and Bone Marrow-Derived Basophil Activation, with a Limited Role for Aging-Associated Microbiota. Immun. Ageing. 2018;15:32. doi: 10.1186/s12979-018-0135-6. PubMed DOI PMC
Mathur S.K., Schwantes E.A., Jarjour N.N., Busse W.W. Age-Related Changes in Eosinophil Function in Human Subjects. Chest. 2008;133:412. doi: 10.1378/chest.07-2114. PubMed DOI PMC
Fung I.T.H., Sankar P., Zhang Y., Robison L.S., Zhao X., D’Souza S.S., Salinero A.E., Yue W., Qian J., Kuentzel M.L., et al. Activation of Group 2 Innate Lymphoid Cells Alleviates Aging-Associated Cognitive Decline. J. Exp. Med. 2020;217:e20190915. doi: 10.1084/jem.20190915. PubMed DOI PMC
D’Souza S.S., Shen X., Fung I.T.H., Ye L., Kuentzel M., Chittur S.V., Furuya Y., Siebel C.W., Maillard I.P., Metzger D.W., et al. Compartmentalized Effects of Aging on Group 2 Innate Lymphoid Cell Development and Function. Aging Cell. 2019;18:e13019. doi: 10.1111/acel.13019. PubMed DOI PMC
Zheng R., Zhang Y., Zhang K., Yuan Y., Jia S., Liu J. The Complement System, Aging, and Aging-Related Diseases. Int. J. Mol. Sci. 2022;23:8689. doi: 10.3390/ijms23158689. PubMed DOI PMC
Fulop T., Larbi A., Pawelec G., Khalil A., Cohen A.A., Hirokawa K., Witkowski J.M., Franceschi C. Immunology of Aging: The Birth of Inflammaging. Clin. Rev. Allergy Immunol. 2021;64:109–122. doi: 10.1007/s12016-021-08899-6. PubMed DOI PMC
Conway J., A Duggal N. Ageing of the Gut Microbiome: Potential Influences on Immune Senescence and Inflammageing. Ageing Res. Rev. 2021;68:101323. doi: 10.1016/j.arr.2021.101323. PubMed DOI
Santos-Moreno P., Burgos-Angulo G., Martinez-Ceballos M.A., Pizano A., Echeverri D., Bautista-Niño P.K., Roks A.J.M., Rojas-Villarraga A. Inflammaging as a Link between Autoimmunity and Cardiovascular Disease: The Case of Rheumatoid Arthritis. RMD Open. 2021;7:e001470. doi: 10.1136/rmdopen-2020-001470. PubMed DOI PMC
Calcinotto A., Kohli J., Zagato E., Pellegrini L., Demaria M., Alimonti A. Cellular Senescence: Aging, Cancer, and Injury. Physiol. Rev. 2019;99:1047–1078. doi: 10.1152/physrev.00020.2018. PubMed DOI
Navas L.E., Carnero A. NAD+ Metabolism, Stemness, the Immune Response, and Cancer. Signal Transduct. Target. Ther. 2021;6:2. doi: 10.1038/s41392-020-00354-w. PubMed DOI PMC
Ferrucci L., Fabbri E. Inflammageing: Chronic Inflammation in Ageing, Cardiovascular Disease, and Frailty. Nat. Rev. Cardiol. 2018;15:505–522. doi: 10.1038/s41569-018-0064-2. PubMed DOI PMC
Rodriguez J.E., Naigeon M., Goldschmidt V., Roulleaux Dugage M., Seknazi L., Danlos F.X., Champiat S., Marabelle A., Michot J.M., Massard C., et al. Immunosenescence, Inflammaging, and Cancer Immunotherapy Efficacy. Expert Rev. Anticancer Ther. 2022;22:915–926. doi: 10.1080/14737140.2022.2098718. PubMed DOI
Serrano-López J., Martín-Antonio B. Inflammaging, an Imbalanced Immune Response That Needs to Be Restored for Cancer Prevention and Treatment in the Elderly. Cells. 2021;10:2562. doi: 10.3390/cells10102562. PubMed DOI PMC
de Toda I.M., Maté I., Vida C., Cruces J., De la Fuente M. Immune Function Parameters as Markers of Biological Age and Predictors of Longevity. Aging. 2016;8:3110–3119. doi: 10.18632/aging.101116. PubMed DOI PMC
Puzianowska-Kuźnicka M., Owczarz M., Wieczorowska-Tobis K., Nadrowski P., Chudek J., Slusarczyk P., Skalska A., Jonas M., Franek E., Mossakowska M. Interleukin-6 and C-Reactive Protein, Successful Aging, and Mortality: The PolSenior Study. Immun. Ageing. 2016;13:21. doi: 10.1186/s12979-016-0076-x. PubMed DOI PMC
Milan-Mattos J.C., Anibal F.F., Perseguini N.M., Minatel V., Rehder-Santos P., Castro C.A., Vasilceac F.A., Mattiello S.M., Faccioli L.H., Catai A.M. Effects of Natural Aging and Gender on Pro-Inflammatory Markers. Braz. J. Med. Biol. Res. 2019;52:e8392. doi: 10.1590/1414-431x20198392. PubMed DOI PMC
Squarzoni S., Schena E., Sabatelli P., Mattioli E., Capanni C., Cenni V., D’Apice M.R., Andrenacci D., Sarli G., Pellegrino V., et al. Interleukin-6 Neutralization Ameliorates Symptoms in Prematurely Aged Mice. Aging Cell. 2021;20:e13285. doi: 10.1111/acel.13285. PubMed DOI PMC
Groblewska M., Mroczko B., Wereszczyńska-Siemiątkowska U., Kȩdra B., Łukaszewicz M., Baniukiewicz A., Szmitkowski M. Serum Interleukin 6 (IL-6) and C-Reactive Protein (CRP) Levels in Colorectal Adenoma and Cancer Patients. Clin. Chem. Lab. Med. 2008;46:1423–1428. doi: 10.1515/CCLM.2008.278. PubMed DOI
Łukaszewicz-Zając M., Mroczko B. Circulating Biomarkers of Colorectal Cancer (CRC)-Their Utility in Diagnosis and Prognosis. J. Clin. Med. 2021;10:2391. doi: 10.3390/jcm10112391. PubMed DOI PMC
Laino A.S., Woods D., Vassallo M., Qian X., Tang H., Wind-Rotolo M., Weber J. Serum Interleukin-6 and C-Reactive Protein Are Associated with Survival in Melanoma Patients Receiving Immune Checkpoint Inhibition. J. Immunother. Cancer. 2020;8:e000842. doi: 10.1136/jitc-2020-000842. PubMed DOI PMC
Mancinelli L., Intini G. Age-Associated Declining of the Regeneration Potential of Skeletal Stem/Progenitor Cells. Front. Physiol. 2023;14:121. doi: 10.3389/fphys.2023.1087254. PubMed DOI PMC
Schüler S.C., Gebert N., Ori A. Stem Cell Aging: The Upcoming Era of Proteins and Metabolites. Mech Ageing Dev. 2020;190:111288. doi: 10.1016/j.mad.2020.111288. PubMed DOI
Mi L., Hu J., Li N., Gao J., Huo R., Peng X., Zhang N., Liu Y., Zhao H., Liu R., et al. The Mechanism of Stem Cell Aging. Stem Cell Rev. Rep. 2022;18:1281–1293. doi: 10.1007/s12015-021-10317-5. PubMed DOI PMC
Dorshkind K., Höfer T., Montecino-Rodriguez E., Pioli P.D., Rodewald H.R. Do Haematopoietic Stem Cells Age? Nat. Rev. Immunol. 2020;20:196. doi: 10.1038/s41577-019-0236-2. PubMed DOI PMC
Mejia-Ramirez E., Florian M.C. Understanding Intrinsic Hematopoietic Stem Cell Aging. Haematologica. 2020;105:22. doi: 10.3324/haematol.2018.211342. PubMed DOI PMC
Yang Y.H.K., Ogando C.R., Wang See C., Chang T.Y., Barabino G.A. Changes in Phenotype and Differentiation Potential of Human Mesenchymal Stem Cells Aging in Vitro. Stem Cell Res. Ther. 2018;9:131. doi: 10.1186/s13287-018-0876-3. PubMed DOI PMC
Zaim M., Karaman S., Cetin G., Isik S. Donor Age and Long-Term Culture Affect Differentiation and Proliferation of Human Bone Marrow Mesenchymal Stem Cells. Ann. Hematol. 2012;91:1175–1186. doi: 10.1007/s00277-012-1438-x. PubMed DOI
Weng Z., Wang Y., Ouchi T., Liu H., Qiao X., Wu C., Zhao Z., Li L., Li B. Mesenchymal Stem/Stromal Cell Senescence: Hallmarks, Mechanisms, and Combating Strategies. Stem Cells Transl. Med. 2022;11:356–371. doi: 10.1093/stcltm/szac004. PubMed DOI PMC
Liu J., Ding Y., Liu Z., Liang X. Senescence in Mesenchymal Stem Cells: Functional Alterations, Molecular Mechanisms, and Rejuvenation Strategies. Front. Cell Dev. Biol. 2020;8:258. doi: 10.3389/fcell.2020.00258. PubMed DOI PMC
Walcher L., Kistenmacher A.K., Suo H., Kitte R., Dluczek S., Strauß A., Blaudszun A.R., Yevsa T., Fricke S., Kossatz-Boehlert U. Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies. Front. Immunol. 2020;11:1280. doi: 10.3389/fimmu.2020.01280. PubMed DOI PMC
Zhang D.Y., Monteiro M.J., Liu J.P., Gu W.Y. Mechanisms of Cancer Stem Cell Senescence: Current Understanding and Future Perspectives. Clin. Exp. Pharmacol. Physiol. 2021;48:1185–1202. doi: 10.1111/1440-1681.13528. PubMed DOI
Wang C., Hao X., Zhang R. Targeting Cellular Senescence to Combat Cancer and Ageing. Mol. Oncol. 2022;16:3319. doi: 10.1002/1878-0261.13266. PubMed DOI PMC
Regmi S.G., Rolland S.G., Conradt B. Age-Dependent Changes in Mitochondrial Morphology and Volume Are Not Predictors of Lifespan. Aging. 2014;6:118. doi: 10.18632/aging.100639. PubMed DOI PMC
Liu Y.J., McIntyre R.L., Janssens G.E., Houtkooper R.H. Mitochondrial Fission and Fusion: A Dynamic Role in Aging and Potential Target for Age-Related Disease. Mech. Ageing Dev. 2020;186:111212. doi: 10.1016/j.mad.2020.111212. PubMed DOI
Chen G., Kroemer G., Kepp O. Mitophagy: An Emerging Role in Aging and Age-Associated Diseases. Front. Cell Dev. Biol. 2020;8:200. doi: 10.3389/fcell.2020.00200. PubMed DOI PMC
Chu C.H., Tseng W.W., Hsu C.M., Wei A.C. Image Analysis of the Mitochondrial Network Morphology with Applications in Cancer Research. Front. Phys. 2022;10:855775. doi: 10.3389/fphy.2022.855775. DOI
Grieco J.P., Allen M.E., Perry J.B., Wang Y., Song Y., Rohani A., Compton S.L.E., Smyth J.W., Swami N.S., Brown D.A., et al. Progression-Mediated Changes in Mitochondrial Morphology Promotes Adaptation to Hypoxic Peritoneal Conditions in Serous Ovarian Cancer. Front. Oncol. 2021;10:600113. doi: 10.3389/fonc.2020.600113. PubMed DOI PMC
Payne B.A.I., Wilson I.J., Yu-Wai-Man P., Coxhead J., Deehan D., Horvath R., Taylor R.W., Samuels D.C., Santibanez-Koref M., Chinnery P.F. Universal Heteroplasmy of Human Mitochondrial DNA. Hum. Mol. Genet. 2013;22:384–390. doi: 10.1093/hmg/dds435. PubMed DOI PMC
Yan C., Duanmu X., Zeng L., Liu B., Song Z. Mitochondrial DNA: Distribution, Mutations, and Elimination. Cells. 2019;8:379. doi: 10.3390/cells8040379. PubMed DOI PMC
Sanchez-Contreras M., Kennedy S.R. The Complicated Nature of Somatic MtDNA Mutations in Aging. Front. Aging. 2022;2:83. doi: 10.3389/fragi.2021.805126. PubMed DOI PMC
Maximov V.N., Malyutina S.K., Orlov P.S., Ivanoschuk D.E., Mikhailova S.V., Shapkina M.Y., Hubacek J., Holmes M., Bobak M., Voevoda M.I. Copy Number of the Mitochondrial DNA of Leucocytes as an Aging Marker and Risk Factors for the Development of Age-Related Diseases in Humans. Adv. Gerontol. 2020;10:1–8. doi: 10.1134/S2079057020010129. PubMed DOI
Scheid A.D., Beadnell T.C., Welch D.R. Roles of Mitochondria in the Hallmarks of Metastasis. Br. J. Cancer. 2020;124:124–135. doi: 10.1038/s41416-020-01125-8. PubMed DOI PMC
Bowman A., Birch-Machin M.A. Age-Dependent Decrease of Mitochondrial Complex II Activity in Human Skin Fibroblasts. J. Investig. Dermatol. 2016;136:912–919. doi: 10.1016/j.jid.2016.01.017. PubMed DOI
Boffoli D., Scacco S.C., Vergari R., Solarino G., Santacroce G., Papa S. Decline with Age of the Respiratory Chain Activity in Human Skeletal Muscle. BBA Mol. Basis Dis. 1994;1226:73–82. doi: 10.1016/0925-4439(94)90061-2. PubMed DOI
Greaves L.C., Barron M.J., Plusa S., Kirkwood T.B., Mathers J.C., Taylor R.W., Turnbull D.M. Defects in Multiple Complexes of the Respiratory Chain Are Present in Ageing Human Colonic Crypts. Exp. Gerontol. 2010;45:573–579. doi: 10.1016/j.exger.2010.01.013. PubMed DOI PMC
Özsoy M., Zimmermann F.A., Feichtinger R.G., Mayr J.A., Kofler B., Neureiter D., Klieser E., Schütz S., Weghuber D., Schneider A.M. Changes in the Expression of Oxidative Phosphorylation Complexes in the Aging Intestinal Mucosa. Exp. Gerontol. 2020;135:110924. doi: 10.1016/j.exger.2020.110924. PubMed DOI
Raimondi V., Ciccarese F., Ciminale V. Oncogenic Pathways and the Electron Transport Chain: A DangeROS Liaison. Br. J. Cancer. 2019;122:168–181. doi: 10.1038/s41416-019-0651-y. PubMed DOI PMC
Wall S.W., Sanchez L., Tuttle K.S., Pearson S.J., Soma S., Wyatt G.L., Carter H.N., Jenschke R.M., Tan L., Martinez S.A., et al. Noncanonical Role of Singleminded-2s in Mitochondrial Respiratory Chain Formation in Breast Cancer. Exp. Mol. Med. 2023;55:1046–1063. doi: 10.1038/s12276-023-00996-0. PubMed DOI PMC
Yang Y., Sauve A.A. Assays for Determination of Cellular and Mitochondrial NAD+ and NADH Content. Methods Mol. Biol. 2021;2310:271–285. doi: 10.1007/978-1-0716-1433-4_15. PubMed DOI
Li W., Sauve A.A. NAD+ content and Its Role in Mitochondria. Methods Mol. Biol. 2015;1241:39–48. PubMed
Massudi H., Grant R., Braidy N., Guest J., Farnsworth B., Guillemin G.J. Age-Associated Changes in Oxidative Stress and NAD+ Metabolism in Human Tissue. PLoS ONE. 2012;7:e42357. doi: 10.1371/journal.pone.0042357. PubMed DOI PMC
Zhu X.H., Lu M., Lee B.Y., Ugurbil K., Chen W. In Vivo NAD Assay Reveals the Intracellular NAD Contents and Redox State in Healthy Human Brain and Their Age Dependences. Proc. Natl. Acad. Sci. USA. 2015;112:2876–2881. doi: 10.1073/pnas.1417921112. PubMed DOI PMC
Clement J., Wong M., Poljak A., Sachdev P., Braidy N. The Plasma NAD+ Metabolome Is Dysregulated in “Normal” Aging. Rejuvenation Res. 2019;22:121–130. doi: 10.1089/rej.2018.2077. PubMed DOI PMC
Karas A., Holmannova D., Borsky P., Fiala Z., Andrys C., Hamakova K., Svadlakova T., Palicka V., Krejsek J., Rehacek V., et al. Significantly Altered Serum Levels of NAD, AGE, RAGE, CRP, and Elastin as Potential Biomarkers of Psoriasis and Aging-A Case-Control Study. Biomedicines. 2022;10:1133. doi: 10.3390/biomedicines10051133. PubMed DOI PMC
Da Veiga Moreira J., Hamraz M., Abolhassani M., Bigan E., Pérès S., Paulevé L., Nogueira M.L., Steyaert J.M., Schwartz L. The Redox Status of Cancer Cells Supports Mechanisms behind the Warburg Effect. Metabolites. 2016;6:33. doi: 10.3390/metabo6040033. PubMed DOI PMC
Wilk A., Hayat F., Cunningham R., Li J., Garavaglia S., Zamani L., Ferraris D.M., Sykora P., Andrews J., Clark J., et al. Extracellular NAD+ Enhances PARP-Dependent DNA Repair Capacity Independently of CD73 Activity. Sci. Rep. 2020;10:651. doi: 10.1038/s41598-020-57506-9. PubMed DOI PMC
Montero R., Yubero D., Villarroya J., Henares D., Jou C., Rodríguez M.A., Ramos F., Nascimento A., Ortez C.I., Campistol J., et al. GDF-15 Is Elevated in Children with Mitochondrial Diseases and Is Induced by Mitochondrial Dysfunction. PLoS ONE. 2016;11:e0148709. doi: 10.1371/journal.pone.0148709. PubMed DOI PMC
Conte M., Martucci M., Mosconi G., Chiariello A., Cappuccilli M., Totti V., Santoro A., Franceschi C., Salvioli S. GDF15 Plasma Level Is Inversely Associated with Level of Physical Activity and Correlates with Markers of Inflammation and Muscle Weakness. Front. Immunol. 2020;11:915. doi: 10.3389/fimmu.2020.00915. PubMed DOI PMC
Liu H., Huang Y., Lyu Y., Dai W., Tong Y., Li Y. GDF15 as a Biomarker of Ageing. Exp. Gerontol. 2021;146:111228. doi: 10.1016/j.exger.2021.111228. PubMed DOI
Welsh P., Kimenai D.M., Marioni R.E., Hayward C., Campbell A., Porteous D., Mills N.L., O’Rahilly S., Sattar N. Reference Ranges for GDF-15, and Risk Factors Associated with GDF-15, in a Large General Population Cohort. Clin. Chem. Lab. Med. 2022;60:1820–1829. doi: 10.1515/cclm-2022-0135. PubMed DOI PMC
Siddiqui J.A., Pothuraju R., Khan P., Sharma G., Muniyan S., Seshacharyulu P., Jain M., Nasser M.W., Batra S.K. Pathophysiological Role of Growth Differentiation Factor 15 (GDF15) in Obesity, Cancer, and Cachexia. Cytokine Growth Factor. Rev. 2022;64:71–83. doi: 10.1016/j.cytogfr.2021.11.002. PubMed DOI PMC
Lungulescu C., Sur D., Răileanu Ș., Dumitru Ștefania M., Mateianu E.A., Lungulescu C.V. GDF-15 Signaling Leading to Epithelial-to-Mesenchymal Transition in Colorectal Cancer–A Literature Review. J. Med. Radiat. Oncol. 2022;2:1–7. doi: 10.53011/JMRO.2022.01.01. DOI
Vocka M., Langer D., Fryba V., Petrtyl J., Hanus T., Kalousova M., Zima T., Petruzelka L. Growth/Differentiation Factor 15 (GDF-15) as New Potential Serum Marker in Patients with Metastatic Colorectal Cancer. Cancer Biomark. 2018;21:869–874. doi: 10.3233/CBM-170792. PubMed DOI
Suzuki H., Mitsunaga S., Ikeda M., Aoyama T., Yoshizawa K., Yoshimatsu H., Kawai N., Masuda M., Miura T., Ochiai A. Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer. Cancers. 2021;13:4842. doi: 10.3390/cancers13194842. PubMed DOI PMC
Rencelj A., Gvozdenovic N., Cemazar M. MitomiRs: Their Roles in Mitochondria and Importance in Cancer Cell Metabolism. Radiol. Oncol. 2021;55:379. doi: 10.2478/raon-2021-0042. PubMed DOI PMC
John A., Kubosumi A., Reddy P.H. Mitochondrial MicroRNAs in Aging and Neurodegenerative Diseases. Cells. 2020;9:1345. doi: 10.3390/cells9061345. PubMed DOI PMC
Rivera J., Gangwani L., Kumar S. Mitochondria Localized MicroRNAs: An Unexplored MiRNA Niche in Alzheimer’s Disease and Aging. Cells. 2023;12:742. doi: 10.3390/cells12050742. PubMed DOI PMC
Purohit P.K., Saini N. Mitochondrial MicroRNA (MitomiRs) in Cancer and Complex Mitochondrial Diseases: Current Status and Future Perspectives. Cell. Mol. Life Sci. 2021;78:1405–1421. doi: 10.1007/s00018-020-03670-0. PubMed DOI PMC
Fan S., Tian T., Chen W., Lv X., Lei X., Zhang H., Sun S., Cai L., Pan G., He L., et al. Mitochondrial MiRNA Determines Chemoresistance by Reprogramming Metabolism and Regulating Mitochondrial Transcription. Cancer Res. 2019;79:1069–1084. doi: 10.1158/0008-5472.CAN-18-2505. PubMed DOI PMC
Hou K., Wu Z.X., Chen X.Y., Wang J.Q., Zhang D., Xiao C., Zhu D., Koya J.B., Wei L., Li J., et al. Microbiota in Health and Diseases. Signal Transduct. Target. Ther. 2022;7:135. doi: 10.1038/s41392-022-00974-4. PubMed DOI PMC
Rinninella E., Tohumcu E., Raoul P., Fiorani M., Cintoni M., Mele M.C., Cammarota G., Gasbarrini A., Ianiro G. The Role of Diet in Shaping Human Gut Microbiota. Best. Pract. Res. Clin. Gastroenterol. 2023;62:101828. doi: 10.1016/j.bpg.2023.101828. PubMed DOI
Ghosh T.S., Das M., Jeffery I.B., O’Toole P.W. Adjusting for Age Improves Identification of Gut Microbiome Alterations in Multiple Diseases. Elife. 2020;9:e50240. doi: 10.7554/eLife.50240. PubMed DOI PMC
Wu L., Xie X., Li Y., Liang T., Zhong H., Yang L., Xi Y., Zhang J., Ding Y., Wu Q. Gut Microbiota as an Antioxidant System in Centenarians Associated with High Antioxidant Activities of Gut-Resident Lactobacillus. npj Biofilms Microbiomes. 2022;8:102. doi: 10.1038/s41522-022-00366-0. PubMed DOI PMC
Li C., Luan Z., Zhao Y., Chen J., Yang Y., Wang C., Jing Y., Qi S., Li Z., Guo H., et al. Deep Insights into the Gut Microbial Community of Extreme Longevity in South Chinese Centenarians by Ultra-Deep Metagenomics and Large-Scale Culturomics. npj Biofilms Microbiomes. 2022;8:28. doi: 10.1038/s41522-022-00282-3. PubMed DOI PMC
Wilmanski T., Diener C., Rappaport N., Patwardhan S., Wiedrick J., Lapidus J., Earls J.C., Zimmer A., Glusman G., Robinson M., et al. Gut Microbiome Pattern Reflects Healthy Aging and Predicts Survival in Humans. Nat. Metab. 2021;3:274. doi: 10.1038/s42255-021-00348-0. PubMed DOI PMC
Khan A.A., Sirsat A.T., Singh H., Cash P. Microbiota and Cancer: Current Understanding and Mechanistic Implications. Clin. Transl. Oncol. 2022;24:193. doi: 10.1007/s12094-021-02690-x. PubMed DOI PMC
Fan X., Jin Y., Chen G., Ma X., Zhang L. Gut Microbiota Dysbiosis Drives the Development of Colorectal Cancer. Digestion. 2021;102:508–515. doi: 10.1159/000508328. PubMed DOI
Zhang X., Yu D., Wu D., Gao X., Shao F., Zhao M., Wang J., Ma J., Wang W., Qin X., et al. Tissue-Resident Lachnospiraceae Family Bacteria Protect against Colorectal Carcinogenesis by Promoting Tumor Immune Surveillance. Cell Host Microbe. 2023;31:418–432.e8. doi: 10.1016/j.chom.2023.01.013. PubMed DOI