[Skin aging-cellular senescence : What is the future?]
Hautalterung – zelluläre Seneszenz : Wohin geht die Reise?
Organ aging
Rejuvenation
Senolytics
Senomorphics
Skin aging
Journal
Dermatologie (Heidelberg, Germany)
ISSN: 2731-7013
Titre abrégé: Dermatologie (Heidelb)
Pays: Germany
ID NLM: 9918384885206676
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
accepted:
04
07
2023
medline:
6
9
2023
pubmed:
28
8
2023
entrez:
28
8
2023
Statut:
ppublish
Résumé
Cellular senescence is the main cause of skin and organ aging and is associated with a wide range of aging-related diseases. To understand which senolytics, senomorphics, and cell-based therapies have been developed to alleviate and even rejuvenate skin aging and reduce cellular senescence. Basic literature for the mode of action of senolytics and senomorphics and their clinical perspectives in daily routine are discussed. Various causes lead to mitochondrial dysfunction and the activation of pro-aging signaling pathways, which eventually lead to cellular senescence with degradation of structural proteins of the dermal connective tissue and severe suppression of regenerative stem cell niches of the skin. Depletion of senescent cells suppress skin aging and enforce rejuvenation of skin and other organs and their function. The removal of senescent cells by cells of the native immune system is severely disturbed during aging. Selected senolytics and senomorphics are approved and are already on the market. HINTERGRUND: Zelluläre Seneszenz ist die Hauptursache für die Haut- und Organalterung mit Ausprägung zahlreicher altersassoziierter Erkrankungen. Welche innovativen therapeutischen Strategien zum Einsatz von Senolytika, Senomorphika und Zelltherapien gibt es, um die Organalterung und die Hautalterung zu vermindern und eine Rejuvenierung zu erzielen. Es werden eine Auswertung und Literaturübersicht zur Wirkweise von Senolytika und Senomorphika, eine Diskussion von Grundlagenarbeiten und klinische Perspektiven gegeben. Verschiedene Ursachen führen über mitochondriale Dysfunktion und Aktivierung von Alterungssignalwegen zur zellulären Seneszenz mit einem Abbau des dermalen Bindegewebes und Unterdrückung der regenerativen Stammzellnischen. Depletion von seneszenten Zellen hemmen die Alterung und können zur Rejuvenierung der Haut, anderer Organe und deren Funktion führen. Die Eliminierung der seneszenten Zellen durch Zellen des Immunsystems ist im Alter gestört. Einzelne Senolytika und Senomorphika sind bereits zugelassen.
Sections du résumé
BACKGROUND
BACKGROUND
Cellular senescence is the main cause of skin and organ aging and is associated with a wide range of aging-related diseases.
OBJECTIVES
OBJECTIVE
To understand which senolytics, senomorphics, and cell-based therapies have been developed to alleviate and even rejuvenate skin aging and reduce cellular senescence.
METHODS
METHODS
Basic literature for the mode of action of senolytics and senomorphics and their clinical perspectives in daily routine are discussed.
RESULTS
RESULTS
Various causes lead to mitochondrial dysfunction and the activation of pro-aging signaling pathways, which eventually lead to cellular senescence with degradation of structural proteins of the dermal connective tissue and severe suppression of regenerative stem cell niches of the skin.
CONCLUSIONS
CONCLUSIONS
Depletion of senescent cells suppress skin aging and enforce rejuvenation of skin and other organs and their function. The removal of senescent cells by cells of the native immune system is severely disturbed during aging. Selected senolytics and senomorphics are approved and are already on the market.
ZUSAMMENFASSUNG
UNASSIGNED
HINTERGRUND: Zelluläre Seneszenz ist die Hauptursache für die Haut- und Organalterung mit Ausprägung zahlreicher altersassoziierter Erkrankungen.
FRAGESTELLUNG
UNASSIGNED
Welche innovativen therapeutischen Strategien zum Einsatz von Senolytika, Senomorphika und Zelltherapien gibt es, um die Organalterung und die Hautalterung zu vermindern und eine Rejuvenierung zu erzielen.
MATERIAL UND METHODE
UNASSIGNED
Es werden eine Auswertung und Literaturübersicht zur Wirkweise von Senolytika und Senomorphika, eine Diskussion von Grundlagenarbeiten und klinische Perspektiven gegeben.
ERGEBNISSE
UNASSIGNED
Verschiedene Ursachen führen über mitochondriale Dysfunktion und Aktivierung von Alterungssignalwegen zur zellulären Seneszenz mit einem Abbau des dermalen Bindegewebes und Unterdrückung der regenerativen Stammzellnischen.
SCHLUSSFOLGERUNGEN
UNASSIGNED
Depletion von seneszenten Zellen hemmen die Alterung und können zur Rejuvenierung der Haut, anderer Organe und deren Funktion führen. Die Eliminierung der seneszenten Zellen durch Zellen des Immunsystems ist im Alter gestört. Einzelne Senolytika und Senomorphika sind bereits zugelassen.
Autres résumés
Type: Publisher
(ger)
HINTERGRUND: Zelluläre Seneszenz ist die Hauptursache für die Haut- und Organalterung mit Ausprägung zahlreicher altersassoziierter Erkrankungen.
Identifiants
pubmed: 37638987
doi: 10.1007/s00105-023-05201-x
pii: 10.1007/s00105-023-05201-x
doi:
Substances chimiques
Senotherapeutics
0
Types de publication
English Abstract
Journal Article
Review
Langues
ger
Sous-ensembles de citation
IM
Pagination
645-656Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
Références
Schlussbericht der Enquête-Kommission „Demographischer Wandel – Herausforderungen unserer älter werdenden Gesellschaft an den Einzelnen und die Politik“ Deutscher Bundestag Drucksache 14/8800 14. Wahlperiode 28. 03. 2002
Baker DJ, Wijshake T, Tchkonia T et al (2011) Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479(7372):232–236
pubmed: 22048312
pmcid: 3468323
Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120(4):513–522
pubmed: 15734683
Campisi J, Kapahi P, Lithgow GJ et al (2019) From discoveries in ageing research to therapeutics for healthy ageing. Nature 571(7764):183–193
pubmed: 31292558
pmcid: 7205183
Childs BG, Durik M, Baker DJ et al (2015) Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat Med 21(12):1424–1435
pubmed: 26646499
pmcid: 4748967
Childs BG, Gluscevic M, Baker DJ et al (2017) Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov 16(10):718–735
pubmed: 28729727
pmcid: 5942225
Ellison-Hughes GM (2020) First evidence that senolytics are effective at decreasing senescent cells in humans. EBioMedicine 56:102473
pubmed: 32454400
pmcid: 7248649
Kirkland JL, Tchkonia T (2020) Senolytic drugs: from discovery to translation. J Intern Med 288(5):518–536
pubmed: 32686219
pmcid: 7405395
Gruber F, Kremslehner C, Eckart L et al (2020) Cell aging and cellular senescence in skin aging—Recent advances in fibroblast and keratinocyte biology. Exp Gerontol 130:110780
pubmed: 31794850
Gunn DA, de Craen AJM, Dick JL et al (2013) Facial appearance reflects human familial longevity and cardiovascular disease risk in healthy individuals. J Gerontol A Biol Sci Med Sci 68(2):145–152
pubmed: 22879455
Castelo-Branco C, Pons F, Gratacós E et al (1994) Relationship between skin collagen and bone changes during aging. Maturitas 18(3):199–206
pubmed: 8015503
Makrantonaki E, Schönknecht P, Hossini AM et al (2010) Skin and brain age together: The role of hormones in the ageing process. Exp Gerontol 45(10):801–813
pubmed: 20719245
Makrantonaki E, Zouboulis CC, German National Genome Research Network 2 (2007) The skin as a mirror of the aging process in the human organism—state of the art and results of the aging research in the German National Genome Research Network 2 (NGFN-2). Exp Gerontol 42(9):879–886
pubmed: 17689905
Blauschun R, Brenneusen P, Wlaschek M et al (2000) The first peak of the UVB irradiation-dependent biphasic induction of vascular endothelial growth factor (VEGF) is due to phosphorylation of the epidermal growth factor receptor and independent of autocrine transforming growth factor α. FEBS Lett 474(2–3):195–200
Krutman J, Bouloc A, Sore G et al (2017) The skin aging exposome. J Dermatol Sci 85(3):152–161
Farsam V, Basu A, Gatzka M et al (2016) Senescent fibroblast-derived Chemerin promotes squamous cell carcinoma migration. Oncotarget 50:83554–83569
Scharffetter-Kochanek K, Schüller J, Meewes C, Hinrichs R, Eich D, Eming S, Wenk J, Wlaschek M (2003) Das chronisch venöse Ulcus cruris. Pathogenese und Bedeutung des „aggressiven Mikromilieus“. J Dtsch Dermatol Ges 1(1):58–67
pubmed: 16285294
Schneider LA, Wlaschek M, Scharffetter-Kochanek K (2003) Hautalterung-Klinik und Pathogenese. J Dtsch Dermatol Ges 1(3):223–232
pubmed: 16285500
Makrantonaki E, Steinhagen-Thiessen E, Nieczaj R et al (2017) Prevalence of skin diseases in hospitalized geriatric patient. Z Gerontol Geriatr 50(6):524–531
pubmed: 27351558
Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cells strains. Exp Cell Res 25:585–621
pubmed: 13905658
Maity P, Singh K, Krug L et al (2021) Persistent JunB activation in fibroblasts disrupts stem cell niche interactions enforcing skin aging. Cell Rep 36(9):109634
pubmed: 34469740
Zou Z, Long X, Zhao Q et al (2021) A single-cell transcriptomic atlas of human skin aging. Dev Cell 56(3):383–397
pubmed: 33238152
Wlaschek M, Maity P, Makrantonaki E, Scharffetter-Kochanek K (2021) Connective tissue and fibroblast senescence in skin aging. J Invest Dermatol 141(4):985–992
pubmed: 33563466
Bodnar AG, Ouellette M, Frolkis M et al (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279:349–352
pubmed: 9454332
Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460
pubmed: 2342578
Yu GL, Bradley JD, Attardi LD et al (1990) In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Nature 344:126–132
pubmed: 1689810
Berneburg M, Gattermann N, Stege H et al (1997) Chronically ultraviolet-exposed human skin shows a higher mutation frequency of mitochondrial DNA as compared to unexposed skin and the hematopoietic system. Photochem Photobiol 66:271–275
pubmed: 9277148
Birch J, Barnes PJ, Passos JF (2018) Mitochondria, telomeres and cell senescence: implications for lung ageing and disease. Pharmacol Ther 183:34–49
pubmed: 28987319
Passos JF, Saretzki G, von Zglinicki T (2007) DNA damage in telomeres and mitochondria during cellular senescence: is there a connection? Nucleic Acids Res 35:7505–7513
pubmed: 17986462
pmcid: 2190715
d’Adda di Fagagna F (2008) Living on a break: cellular senescence as a DNA damage response. Nat Rev Cancer 8:512–522
pubmed: 18574463
Hoeijmakers JHJ (2009) DNA damage, aging, and cancer. N Engl J Med 361:475–485
da Silva PFL, Schumacher B (2019) DNA damage responses in ageing. Open Biol 9:190168
pubmed: 31744423
pmcid: 6893400
Gorgoulis V, Adams PD, Alimonti A et al (2019) Cellular senescence: defining a path forward. Cell 179:813–827
pubmed: 31675495
Braumüller H, Wieder T, Brenner E et al (2013) T‑helper-1-cell cytokines drive cancer into senescence. Nature 494(7437):361–365
pubmed: 23376950
Chondrogianni N, Gonos ES (2010) Proteasome function determines cellular homeostasis and the rate of aging. Adv Exp Med Biol 694:38–46
pubmed: 20886755
Catalgol B, Grune T (2009) Protein pool maintenance during oxidative stress. Curr Pharm Des 15:3043–3051
pubmed: 19754378
Eckhart L, Tschachler E, Gruber F (2019) Autophagic control of skin aging. Front Cell Dev Biol 7:143
pubmed: 31417903
pmcid: 6682604
Gu Y, Han J, Jiang C et al (2020) Biomarkers, oxidative stress and autophagy in skin aging. Ageing Res Rev 59:101036
pubmed: 32105850
Rinnerthaler M, Bischof J, Streubel MK et al (2015) Oxidative stress in aging human skin. Biomolecules 5:545–589
pubmed: 25906193
pmcid: 4496685
Treiber N, Maity P, Singh K et al (2011) Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue. Aging Cell 10:239–254
pubmed: 21108731
Demaria M, Desprez PY, Campisi J et al (2015) Cell autonomous and non-cell autonomous effects of senescent cells in the skin. J Invest Dermatol 135(7):1722–1726
pubmed: 25855157
pmcid: 4466004
Ovadya Y, Krizhanovsky V (2018) Strategies targeting cellular senescence. J Clin Invest 128:1247–1254
pubmed: 29608140
pmcid: 5873866
Meyer P, Maity P, Burkovski A et al (2017) A model of the onset of the senescence associated secretory phenotype after DNA damage induced senescence. PLoS Comput Biol 13(12):e1005741
pubmed: 29206223
pmcid: 5730191
Lozano-Torres B, Estepa-Fernández A, Rovira M et al (2019) The chemistry of senescence. Nat Rev Chem 3:426–441
Acosta JC, Banito A, Wuestefeld T et al (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15:978–990
pubmed: 23770676
pmcid: 3732483
da Silva PFL, Ogrodnik M, Kucheryavenko O et al (2019) The bystander effect contributes to the accumulation of senescent cells in vivo. Aging Cell 18:e12848
pubmed: 30462359
Nelson G, Kucheryavenko O, Wordsworth J et al (2018) The senescent bystander effect is caused by ROS-activated NF-kB signaling. Mech Ageing Dev 170:30–36
pubmed: 28837845
pmcid: 5861994
Weinmüllner R, Zbiral B, Becirovic A et al (2020) Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging. NPJ Aging Mech Dis 6:4
pubmed: 32194977
pmcid: 7060247
Herbig U, Ferreira M, Condel L et al (2006) Cellular senescence in aging primates. Science 311(5765):1257
pubmed: 16456035
Krishnamurthy J, Torrice C, Ramsey MR et al (2004) Ink4a/Arf expression is a biomarker of aging. J Clin Invest 114:1299–1307
pubmed: 15520862
pmcid: 524230
Dimri GP, Lee X, Basile G et al (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 92:9363–9367
pubmed: 7568133
pmcid: 40985
Ressler S, Bartkova J, Niederegger H et al (2006) p16 INK4A is a robust in vivo biomarker of cellular aging in human skin. Aging Cell 5:379–389
pubmed: 16911562
Ho CY, Dreesen O (2021) Faces of cellular senescence in skin aging. Mech Ageing Dev 198:111525
pubmed: 34166688
Tuttle CSL, Waaijer MEC, Slee-Valentijn MS et al (2020) Cellular senescence and chronological age in various human tissues: a systematic review and meta-analysis. Aging Cell 19:e13083
pubmed: 31808308
Ovadya Y, Landsberger T, Leins H et al (2018) Impaired immune surveillance accelerates accumulation of senescent cells and aging. Nat Commun 9:5435
pubmed: 30575733
pmcid: 6303397
Hazeldine J, Hampson P, Lord JM (2012) Reduced release and binding of perforin at the immunological synapse underlies the age-related decline in natural killer cell cytotoxicity. Aging Cell 11:751–759
pubmed: 22642232
Pereira BI, Devine OP, Vukmanovic-Stejic M et al (2019) Senescent cells evade immune clearance via HLA-E-mediated NK and CD8(+) T cell inhibition. Nat Commun 10:2387
pubmed: 31160572
pmcid: 6547655
Baker DJ, Childs BG, Durik M et al (2016) Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 530:184–189
pubmed: 26840489
pmcid: 4845101
van Deursen JM (2014) The role of senescent cells in aging. Nature 509(7501):439–446
pubmed: 24848057
pmcid: 4214092
Zhou X, Franklin RA, Adler M et al (2018) Circuit design features of a stable two-cell system. Cell 172:744–757
pubmed: 29398113
pmcid: 7377352
Fuhrmann-Stroissnigg H, Ling YY, Zhao J et al (2017) Identification of HSP90 inhibitors as a novel class of senolytics. Nat Commun 8:422
pubmed: 28871086
pmcid: 5583353
Kim H, Jang J, Song MJ et al (2022) Attenuation of intrinsic aging of the skin via elimination of senescent dermal fibroblasts. J Eur Acad Dermatol Venereol 36:1125–1135
pubmed: 35274377
Chang J, Wang Y, Shao L et al (2016) Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med 22:78–83
pubmed: 26657143
Kim HN, Chang J, Shao L et al (2017) DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age. Aging Cell 16:693–703
pubmed: 28401730
pmcid: 5506444
Raffaele M, Vinciguerra M (2022) The costs and benefits of senotherapeutics for human health. Lancet Healthy Longev 3:e67–e77
pubmed: 36098323
Justice JN, Nambiar AM, Tchkonia T et al (2019) Senolytics in idiopathic pulmonary fibrosis: results from a first-inhuman, open-label, pilot study. EBioMedicine 40:554–563
pubmed: 30616998
pmcid: 6412088
Hickson LJ, Langhi Prata LGP, Bobart SA et al (2019) Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease. EBioMedicine 47:446–456
pubmed: 31542391
pmcid: 6796530
Lämmermann I, Terlecki-Zaniewicz L, Weinmüllner R et al (2018) Blocking negative effects of senescence in human skin fibroblasts with a plant extract. NPJ Aging Mech Dis 11(4):4
Johmura Y, Yamanaka T, Omori S et al (2021) Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science 371(6526):235–243
Takaya K, Ishii T, Asou T et al (2022) Glutaminase inhibitors rejuvenate human skin via clearance of senescent cells: a study using a mouse/human chimeric model. Aging 14(22):8914–8926
pubmed: 36435512
pmcid: 9740363
Guerrero A, Herranz N, Sun B et al (2019) Cardioglykosides are broad spectrum senolytics. Nat Metab 1:1074–1088
pubmed: 31799499
pmcid: 6887543
Triana-Martínez F, Picallos-Rabina P, Da Silva-Álvarez S et al (2019) Identification and characterization of cardiac-glycosides as senolytic compound. Nat Commun 10(1):4731
pubmed: 31636264
pmcid: 6803708
Baar MP, Brandt RMC, Putavet DA et al (2017) Targeted apoptosis of the senescent cell restores tissue homeostasis in response to chemotoxicity and aging. Cell 169:132–147
pubmed: 28340339
pmcid: 5556182
Ozsvari B, Nuttall JR, Sotgia F et al (2018) Azithromycin and Roxithromycin define a new family of ”senolytic“ drugs that target senescent human fibroblasts. Aging 10(11):3294–3307
pubmed: 30428454
pmcid: 6286845
Vallet-Regí M, Colilla M, Izquierdo-Barba I et al (2017) Mesoporous silica nanoparticles for drug delivery: current insights. Molecules 23(1):47
pubmed: 29295564
pmcid: 5943960
Munoz-Espin D, Rovira M, Galiana I et al (2018) A versatile drug delivery system targeting senescent cells. EMBO Mol Med 10(9):e9355
pubmed: 30012580
pmcid: 6127887
Amor C, Feucht J, Leibold J et al (2020) Senolytic CAR T cells reverse senescence-associated pathologies. Nature 583:127–132
pubmed: 32555459
pmcid: 7583560
Klareskog L, van der Heijde D, de Jager J et al (2004) Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 363(9410):675–681
pubmed: 15001324
Kuemmerle-Deschner JB, Ramos E, Blank N et al (2011) Canakinumab (ACZ885, a fully human IgG1 anti-IL-1β mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS). Arthritis Res Ther 13(1):R34
pubmed: 21356079
pmcid: 3241378
van Rhee F, Wong RS, Munshi N et al (2014) Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol 15(9):966–974
pubmed: 25042199
Mirza R, Koh TJ (2011) Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice. Cytokine 56:256–264
pubmed: 21803601
Vander Beken S, de Vries JC, Meier-Schiesser B et al (2019) Newly defined ATP-binding cassette subfamily B Member 5 positive dermal mesenchymal stem cells promote healing of chronic iron-overload wounds via secretion of interleukin‑1 receptor antagonist. Stem Cells 37:1057–1074
pubmed: 31002437
Kerstan A, Dieter K, Niebergall-Roth E et al (2022) Translational development of ABCB5+ dermal mesenchymal stem cells for therapeutic induction of angiogenesis in non-healing diabetic foot ulcers. Stem Cell Res Ther 13(1):455
pubmed: 36064604
pmcid: 9444095
Goldberg RB, Aroda VR, Bluemke DA et al (2017) Effect of long-term metformin and lifestyle in the diabetes prevention program and its outcome study on coronary artery calcium. Circulation 136:52–64
pubmed: 28476766
pmcid: 5526695
Svensson E, Baggesen LM, Johnsen SP et al (2017) Early glycemic control and magnitude of HbA(1c) reduction predict cardiovascular events and mortality: population-based cohort study of 24,752 metformin initiators. Diabetes Care 40:800–807
pubmed: 28404659
Harrison DE et al (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–395
pubmed: 19587680
pmcid: 2786175
Lamming DW, Ye L, Sabatini DM et al (2013) Rapalogs and mTOR inhibitors as anti-aging therapeutics. J Clin Invest 123:980–989
pubmed: 23454761
pmcid: 3582126
Martin-Montalvo A, Mercken EM, Mitchell SJ et al (2013) Metformin improves healthspan and lifespan in mice. Nat Commun 4:2192
pubmed: 23900241
Wilkinson JE et al (2012) Rapamycin slows aging in mice. Aging Cell 11:675–682
pubmed: 22587563
Mannick JB, Del Guidice G, Lattanzi M et al (2014) mTOR inhibition improves immune function in the elderly. Sci Transl Med 6:268
Mannick JB, Morris M, Hockey H‑UP et al (2018) TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med 10:449
Mannick JB, Teo G, Bernardo P et al (2021) Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials. Lancet Healthy Longev 2:e250–e262
pubmed: 33977284
pmcid: 8102040
Chung CL, Lawrence I, Hoffman M et al (2019) Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial. GeroScience 41:861–869
pubmed: 31761958
pmcid: 6925069
Leins H, Mulaw M, Eiwen K et al (2018) Aged murine hematopoietic stem cells drive aging-associated immune remodeling. Blood 132:565–576
pubmed: 29891535
pmcid: 6137572
Larbi A, Franceschi C, Mazzatti D et al (2008) Aging of the immune system as a prognostic factor for humanlongevity. Physiology (Bethesda) 23:64–74
pubmed: 18400689
Prata LGPL, Ovsyannikova IG, Tchkonia T et al (2018) Senescent cell clearance by the immune system: Emerging therapeutic opportunities. Semin Immunol 40:101275
pubmed: 31088710
Yousefzadeh MJ, Flores RR, Zhu Y et al (2021) An aged immune system drives senescence and ageing of solid organs. Nature 594:100–105
pubmed: 33981041
pmcid: 8684299
Chen X‑K, Yi Z‑N, Wong GT‑C et al (2021) Is exercise a senolytic medicine? A systematic review. Aging Cell 20(1):e13294. https://doi.org/10.1111/acel.13294
doi: 10.1111/acel.13294
pubmed: 33378138
Crane JD, MacNeil LG, Lally JS et al (2015) Exercise-stimulated interleukin-15 is controlled by AMPK and regulatesskin metabolism and aging. Aging Cell 14(4):625–634
pubmed: 25902870
pmcid: 4531076
Aguado J, Sola-Carvajal A, Cancila V et al (2019) Inhibition of DNA-damage response at telomeres approves the detrimental phenotypes of Hutchinson-Gilford-progeria-syndrome. Nat Commun 10(1):4990
pubmed: 31740672
pmcid: 6861280