Skip to main content
Erschienen in: Die Dermatologie 9/2023

28.08.2023 | Hautalterung | Leitthema

Hautalterung – zelluläre Seneszenz

Wohin geht die Reise?

verfasst von: Prof. Dr. med. Karin Scharffetter-Kochanek, Yongfang Wang, Evgenia Makrantonaki, Diana Crisan, Meinhard Wlaschek, Hartmut Geiger, Pallab Maity

Erschienen in: Die Dermatologie | Ausgabe 9/2023

Einloggen, um Zugang zu erhalten

Zusammenfassung

Hintergrund

Zelluläre Seneszenz ist die Hauptursache für die Haut- und Organalterung mit Ausprägung zahlreicher altersassoziierter Erkrankungen.

Fragestellung

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

Es werden eine Auswertung und Literaturübersicht zur Wirkweise von Senolytika und Senomorphika, eine Diskussion von Grundlagenarbeiten und klinische Perspektiven gegeben.

Ergebnisse

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

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.
Literatur
1.
Zurück zum Zitat 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 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
2.
Zurück zum Zitat Baker DJ, Wijshake T, Tchkonia T et al (2011) Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479(7372):232–236PubMedPubMedCentral Baker DJ, Wijshake T, Tchkonia T et al (2011) Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479(7372):232–236PubMedPubMedCentral
3.
Zurück zum Zitat Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120(4):513–522PubMed Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120(4):513–522PubMed
4.
Zurück zum Zitat Campisi J, Kapahi P, Lithgow GJ et al (2019) From discoveries in ageing research to therapeutics for healthy ageing. Nature 571(7764):183–193PubMedPubMedCentral Campisi J, Kapahi P, Lithgow GJ et al (2019) From discoveries in ageing research to therapeutics for healthy ageing. Nature 571(7764):183–193PubMedPubMedCentral
5.
Zurück zum Zitat 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):1424–1435PubMedPubMedCentral 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):1424–1435PubMedPubMedCentral
6.
Zurück zum Zitat Childs BG, Gluscevic M, Baker DJ et al (2017) Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov 16(10):718–735PubMedPubMedCentral Childs BG, Gluscevic M, Baker DJ et al (2017) Senescent cells: an emerging target for diseases of ageing. Nat Rev Drug Discov 16(10):718–735PubMedPubMedCentral
7.
Zurück zum Zitat Ellison-Hughes GM (2020) First evidence that senolytics are effective at decreasing senescent cells in humans. EBioMedicine 56:102473PubMedPubMedCentral Ellison-Hughes GM (2020) First evidence that senolytics are effective at decreasing senescent cells in humans. EBioMedicine 56:102473PubMedPubMedCentral
8.
Zurück zum Zitat Kirkland JL, Tchkonia T (2020) Senolytic drugs: from discovery to translation. J Intern Med 288(5):518–536PubMedPubMedCentral Kirkland JL, Tchkonia T (2020) Senolytic drugs: from discovery to translation. J Intern Med 288(5):518–536PubMedPubMedCentral
9.
Zurück zum Zitat 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 130:110780PubMed 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 130:110780PubMed
10.
Zurück zum Zitat 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):145–152PubMed 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):145–152PubMed
11.
Zurück zum Zitat Castelo-Branco C, Pons F, Gratacós E et al (1994) Relationship between skin collagen and bone changes during aging. Maturitas 18(3):199–206PubMed Castelo-Branco C, Pons F, Gratacós E et al (1994) Relationship between skin collagen and bone changes during aging. Maturitas 18(3):199–206PubMed
12.
Zurück zum Zitat 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):801–813PubMed 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):801–813PubMed
13.
Zurück zum Zitat 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):879–886PubMed 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):879–886PubMed
14.
Zurück zum Zitat 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 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
15.
Zurück zum Zitat Krutman J, Bouloc A, Sore G et al (2017) The skin aging exposome. J Dermatol Sci 85(3):152–161 Krutman J, Bouloc A, Sore G et al (2017) The skin aging exposome. J Dermatol Sci 85(3):152–161
16.
Zurück zum Zitat Farsam V, Basu A, Gatzka M et al (2016) Senescent fibroblast-derived Chemerin promotes squamous cell carcinoma migration. Oncotarget 50:83554–83569 Farsam V, Basu A, Gatzka M et al (2016) Senescent fibroblast-derived Chemerin promotes squamous cell carcinoma migration. Oncotarget 50:83554–83569
17.
Zurück zum Zitat 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):58–67PubMed 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):58–67PubMed
18.
Zurück zum Zitat Schneider LA, Wlaschek M, Scharffetter-Kochanek K (2003) Hautalterung-Klinik und Pathogenese. J Dtsch Dermatol Ges 1(3):223–232PubMed Schneider LA, Wlaschek M, Scharffetter-Kochanek K (2003) Hautalterung-Klinik und Pathogenese. J Dtsch Dermatol Ges 1(3):223–232PubMed
19.
Zurück zum Zitat Makrantonaki E, Steinhagen-Thiessen E, Nieczaj R et al (2017) Prevalence of skin diseases in hospitalized geriatric patient. Z Gerontol Geriatr 50(6):524–531PubMed Makrantonaki E, Steinhagen-Thiessen E, Nieczaj R et al (2017) Prevalence of skin diseases in hospitalized geriatric patient. Z Gerontol Geriatr 50(6):524–531PubMed
20.
Zurück zum Zitat Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cells strains. Exp Cell Res 25:585–621PubMed Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cells strains. Exp Cell Res 25:585–621PubMed
21.
Zurück zum Zitat 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):109634PubMed 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):109634PubMed
22.
Zurück zum Zitat Zou Z, Long X, Zhao Q et al (2021) A single-cell transcriptomic atlas of human skin aging. Dev Cell 56(3):383–397PubMed Zou Z, Long X, Zhao Q et al (2021) A single-cell transcriptomic atlas of human skin aging. Dev Cell 56(3):383–397PubMed
23.
Zurück zum Zitat Wlaschek M, Maity P, Makrantonaki E, Scharffetter-Kochanek K (2021) Connective tissue and fibroblast senescence in skin aging. J Invest Dermatol 141(4):985–992PubMed Wlaschek M, Maity P, Makrantonaki E, Scharffetter-Kochanek K (2021) Connective tissue and fibroblast senescence in skin aging. J Invest Dermatol 141(4):985–992PubMed
24.
Zurück zum Zitat Bodnar AG, Ouellette M, Frolkis M et al (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279:349–352PubMed Bodnar AG, Ouellette M, Frolkis M et al (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279:349–352PubMed
25.
Zurück zum Zitat Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460PubMed Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460PubMed
26.
Zurück zum Zitat Yu GL, Bradley JD, Attardi LD et al (1990) In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Nature 344:126–132PubMed Yu GL, Bradley JD, Attardi LD et al (1990) In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Nature 344:126–132PubMed
27.
Zurück zum Zitat 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 66:271–275PubMed 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 66:271–275PubMed
28.
Zurück zum Zitat Birch J, Barnes PJ, Passos JF (2018) Mitochondria, telomeres and cell senescence: implications for lung ageing and disease. Pharmacol Ther 183:34–49PubMed Birch J, Barnes PJ, Passos JF (2018) Mitochondria, telomeres and cell senescence: implications for lung ageing and disease. Pharmacol Ther 183:34–49PubMed
29.
Zurück zum Zitat Passos JF, Saretzki G, von Zglinicki T (2007) DNA damage in telomeres and mitochondria during cellular senescence: is there a connection? Nucleic Acids Res 35:7505–7513PubMedPubMedCentral Passos JF, Saretzki G, von Zglinicki T (2007) DNA damage in telomeres and mitochondria during cellular senescence: is there a connection? Nucleic Acids Res 35:7505–7513PubMedPubMedCentral
30.
Zurück zum Zitat d’Adda di Fagagna F (2008) Living on a break: cellular senescence as a DNA damage response. Nat Rev Cancer 8:512–522PubMed d’Adda di Fagagna F (2008) Living on a break: cellular senescence as a DNA damage response. Nat Rev Cancer 8:512–522PubMed
31.
Zurück zum Zitat Hoeijmakers JHJ (2009) DNA damage, aging, and cancer. N Engl J Med 361:475–485 Hoeijmakers JHJ (2009) DNA damage, aging, and cancer. N Engl J Med 361:475–485
33.
Zurück zum Zitat Gorgoulis V, Adams PD, Alimonti A et al (2019) Cellular senescence: defining a path forward. Cell 179:813–827PubMed Gorgoulis V, Adams PD, Alimonti A et al (2019) Cellular senescence: defining a path forward. Cell 179:813–827PubMed
34.
Zurück zum Zitat Braumüller H, Wieder T, Brenner E et al (2013) T‑helper-1-cell cytokines drive cancer into senescence. Nature 494(7437):361–365PubMed Braumüller H, Wieder T, Brenner E et al (2013) T‑helper-1-cell cytokines drive cancer into senescence. Nature 494(7437):361–365PubMed
35.
Zurück zum Zitat Chondrogianni N, Gonos ES (2010) Proteasome function determines cellular homeostasis and the rate of aging. Adv Exp Med Biol 694:38–46PubMed Chondrogianni N, Gonos ES (2010) Proteasome function determines cellular homeostasis and the rate of aging. Adv Exp Med Biol 694:38–46PubMed
36.
Zurück zum Zitat Catalgol B, Grune T (2009) Protein pool maintenance during oxidative stress. Curr Pharm Des 15:3043–3051PubMed Catalgol B, Grune T (2009) Protein pool maintenance during oxidative stress. Curr Pharm Des 15:3043–3051PubMed
37.
38.
Zurück zum Zitat Gu Y, Han J, Jiang C et al (2020) Biomarkers, oxidative stress and autophagy in skin aging. Ageing Res Rev 59:101036PubMed Gu Y, Han J, Jiang C et al (2020) Biomarkers, oxidative stress and autophagy in skin aging. Ageing Res Rev 59:101036PubMed
39.
Zurück zum Zitat Rinnerthaler M, Bischof J, Streubel MK et al (2015) Oxidative stress in aging human skin. Biomolecules 5:545–589PubMedPubMedCentral Rinnerthaler M, Bischof J, Streubel MK et al (2015) Oxidative stress in aging human skin. Biomolecules 5:545–589PubMedPubMedCentral
40.
Zurück zum Zitat 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 10:239–254PubMed 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 10:239–254PubMed
41.
Zurück zum Zitat 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):1722–1726PubMedPubMedCentral 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):1722–1726PubMedPubMedCentral
42.
43.
Zurück zum Zitat 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):e1005741PubMedPubMedCentral 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):e1005741PubMedPubMedCentral
44.
Zurück zum Zitat Lozano-Torres B, Estepa-Fernández A, Rovira M et al (2019) The chemistry of senescence. Nat Rev Chem 3:426–441 Lozano-Torres B, Estepa-Fernández A, Rovira M et al (2019) The chemistry of senescence. Nat Rev Chem 3:426–441
45.
Zurück zum Zitat Acosta JC, Banito A, Wuestefeld T et al (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15:978–990PubMedPubMedCentral Acosta JC, Banito A, Wuestefeld T et al (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15:978–990PubMedPubMedCentral
46.
Zurück zum Zitat 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:e12848PubMed 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:e12848PubMed
47.
Zurück zum Zitat Nelson G, Kucheryavenko O, Wordsworth J et al (2018) The senescent bystander effect is caused by ROS-activated NF-kB signaling. Mech Ageing Dev 170:30–36PubMedPubMedCentral Nelson G, Kucheryavenko O, Wordsworth J et al (2018) The senescent bystander effect is caused by ROS-activated NF-kB signaling. Mech Ageing Dev 170:30–36PubMedPubMedCentral
48.
Zurück zum Zitat 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 6:4PubMedPubMedCentral 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 6:4PubMedPubMedCentral
49.
Zurück zum Zitat Herbig U, Ferreira M, Condel L et al (2006) Cellular senescence in aging primates. Science 311(5765):1257PubMed Herbig U, Ferreira M, Condel L et al (2006) Cellular senescence in aging primates. Science 311(5765):1257PubMed
50.
Zurück zum Zitat Krishnamurthy J, Torrice C, Ramsey MR et al (2004) Ink4a/Arf expression is a biomarker of aging. J Clin Invest 114:1299–1307PubMedPubMedCentral Krishnamurthy J, Torrice C, Ramsey MR et al (2004) Ink4a/Arf expression is a biomarker of aging. J Clin Invest 114:1299–1307PubMedPubMedCentral
51.
Zurück zum Zitat 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 92:9363–9367PubMedPubMedCentral 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 92:9363–9367PubMedPubMedCentral
52.
Zurück zum Zitat 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 5:379–389PubMed 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 5:379–389PubMed
53.
Zurück zum Zitat Ho CY, Dreesen O (2021) Faces of cellular senescence in skin aging. Mech Ageing Dev 198:111525PubMed Ho CY, Dreesen O (2021) Faces of cellular senescence in skin aging. Mech Ageing Dev 198:111525PubMed
54.
Zurück zum Zitat 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:e13083PubMed 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:e13083PubMed
55.
Zurück zum Zitat Ovadya Y, Landsberger T, Leins H et al (2018) Impaired immune surveillance accelerates accumulation of senescent cells and aging. Nat Commun 9:5435PubMedPubMedCentral Ovadya Y, Landsberger T, Leins H et al (2018) Impaired immune surveillance accelerates accumulation of senescent cells and aging. Nat Commun 9:5435PubMedPubMedCentral
56.
Zurück zum Zitat 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 11:751–759PubMed 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 11:751–759PubMed
57.
Zurück zum Zitat 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 10:2387PubMedPubMedCentral 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 10:2387PubMedPubMedCentral
58.
Zurück zum Zitat Baker DJ, Childs BG, Durik M et al (2016) Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 530:184–189PubMedPubMedCentral Baker DJ, Childs BG, Durik M et al (2016) Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 530:184–189PubMedPubMedCentral
60.
Zurück zum Zitat Zhou X, Franklin RA, Adler M et al (2018) Circuit design features of a stable two-cell system. Cell 172:744–757PubMedPubMedCentral Zhou X, Franklin RA, Adler M et al (2018) Circuit design features of a stable two-cell system. Cell 172:744–757PubMedPubMedCentral
61.
Zurück zum Zitat Fuhrmann-Stroissnigg H, Ling YY, Zhao J et al (2017) Identification of HSP90 inhibitors as a novel class of senolytics. Nat Commun 8:422PubMedPubMedCentral Fuhrmann-Stroissnigg H, Ling YY, Zhao J et al (2017) Identification of HSP90 inhibitors as a novel class of senolytics. Nat Commun 8:422PubMedPubMedCentral
62.
Zurück zum Zitat 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 36:1125–1135PubMed 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 36:1125–1135PubMed
63.
Zurück zum Zitat Chang J, Wang Y, Shao L et al (2016) Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med 22:78–83PubMed Chang J, Wang Y, Shao L et al (2016) Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med 22:78–83PubMed
64.
Zurück zum Zitat 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 16:693–703PubMedPubMedCentral 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 16:693–703PubMedPubMedCentral
65.
Zurück zum Zitat Raffaele M, Vinciguerra M (2022) The costs and benefits of senotherapeutics for human health. Lancet Healthy Longev 3:e67–e77PubMed Raffaele M, Vinciguerra M (2022) The costs and benefits of senotherapeutics for human health. Lancet Healthy Longev 3:e67–e77PubMed
66.
Zurück zum Zitat Justice JN, Nambiar AM, Tchkonia T et al (2019) Senolytics in idiopathic pulmonary fibrosis: results from a first-inhuman, open-label, pilot study. EBioMedicine 40:554–563PubMedPubMedCentral Justice JN, Nambiar AM, Tchkonia T et al (2019) Senolytics in idiopathic pulmonary fibrosis: results from a first-inhuman, open-label, pilot study. EBioMedicine 40:554–563PubMedPubMedCentral
67.
Zurück zum Zitat 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 47:446–456PubMedPubMedCentral 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 47:446–456PubMedPubMedCentral
68.
Zurück zum Zitat 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 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
69.
Zurück zum Zitat Johmura Y, Yamanaka T, Omori S et al (2021) Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science 371(6526):235–243 Johmura Y, Yamanaka T, Omori S et al (2021) Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science 371(6526):235–243
70.
Zurück zum Zitat 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):8914–8926PubMedPubMedCentral 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):8914–8926PubMedPubMedCentral
71.
Zurück zum Zitat Guerrero A, Herranz N, Sun B et al (2019) Cardioglykosides are broad spectrum senolytics. Nat Metab 1:1074–1088PubMedPubMedCentral Guerrero A, Herranz N, Sun B et al (2019) Cardioglykosides are broad spectrum senolytics. Nat Metab 1:1074–1088PubMedPubMedCentral
72.
Zurück zum Zitat 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):4731PubMedPubMedCentral 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):4731PubMedPubMedCentral
73.
Zurück zum Zitat 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 169:132–147PubMedPubMedCentral 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 169:132–147PubMedPubMedCentral
74.
Zurück zum Zitat 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):3294–3307PubMedPubMedCentral 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):3294–3307PubMedPubMedCentral
75.
Zurück zum Zitat Vallet-Regí M, Colilla M, Izquierdo-Barba I et al (2017) Mesoporous silica nanoparticles for drug delivery: current insights. Molecules 23(1):47PubMedPubMedCentral Vallet-Regí M, Colilla M, Izquierdo-Barba I et al (2017) Mesoporous silica nanoparticles for drug delivery: current insights. Molecules 23(1):47PubMedPubMedCentral
76.
Zurück zum Zitat Munoz-Espin D, Rovira M, Galiana I et al (2018) A versatile drug delivery system targeting senescent cells. EMBO Mol Med 10(9):e9355PubMedPubMedCentral Munoz-Espin D, Rovira M, Galiana I et al (2018) A versatile drug delivery system targeting senescent cells. EMBO Mol Med 10(9):e9355PubMedPubMedCentral
77.
Zurück zum Zitat Amor C, Feucht J, Leibold J et al (2020) Senolytic CAR T cells reverse senescence-associated pathologies. Nature 583:127–132PubMedPubMedCentral Amor C, Feucht J, Leibold J et al (2020) Senolytic CAR T cells reverse senescence-associated pathologies. Nature 583:127–132PubMedPubMedCentral
78.
Zurück zum Zitat 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):675–681PubMed 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):675–681PubMed
79.
Zurück zum Zitat 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):R34PubMedPubMedCentral 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):R34PubMedPubMedCentral
80.
Zurück zum Zitat 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):966–974PubMed 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):966–974PubMed
81.
Zurück zum Zitat Mirza R, Koh TJ (2011) Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice. Cytokine 56:256–264PubMed Mirza R, Koh TJ (2011) Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice. Cytokine 56:256–264PubMed
82.
Zurück zum Zitat 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 37:1057–1074PubMed 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 37:1057–1074PubMed
83.
Zurück zum Zitat 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):455PubMedPubMedCentral 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):455PubMedPubMedCentral
84.
Zurück zum Zitat 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 136:52–64PubMedPubMedCentral 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 136:52–64PubMedPubMedCentral
85.
Zurück zum Zitat 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 40:800–807PubMed 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 40:800–807PubMed
86.
Zurück zum Zitat Harrison DE et al (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–395PubMedPubMedCentral Harrison DE et al (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–395PubMedPubMedCentral
87.
Zurück zum Zitat Lamming DW, Ye L, Sabatini DM et al (2013) Rapalogs and mTOR inhibitors as anti-aging therapeutics. J Clin Invest 123:980–989PubMedPubMedCentral Lamming DW, Ye L, Sabatini DM et al (2013) Rapalogs and mTOR inhibitors as anti-aging therapeutics. J Clin Invest 123:980–989PubMedPubMedCentral
88.
Zurück zum Zitat Martin-Montalvo A, Mercken EM, Mitchell SJ et al (2013) Metformin improves healthspan and lifespan in mice. Nat Commun 4:2192PubMed Martin-Montalvo A, Mercken EM, Mitchell SJ et al (2013) Metformin improves healthspan and lifespan in mice. Nat Commun 4:2192PubMed
89.
Zurück zum Zitat Wilkinson JE et al (2012) Rapamycin slows aging in mice. Aging Cell 11:675–682PubMed Wilkinson JE et al (2012) Rapamycin slows aging in mice. Aging Cell 11:675–682PubMed
90.
Zurück zum Zitat 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, Del Guidice G, Lattanzi M et al (2014) mTOR inhibition improves immune function in the elderly. Sci Transl Med 6:268
91.
Zurück zum Zitat 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, Morris M, Hockey H‑UP et al (2018) TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med 10:449
92.
Zurück zum Zitat 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–e262PubMedPubMedCentral 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–e262PubMedPubMedCentral
93.
Zurück zum Zitat 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 41:861–869PubMedPubMedCentral 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 41:861–869PubMedPubMedCentral
94.
Zurück zum Zitat Leins H, Mulaw M, Eiwen K et al (2018) Aged murine hematopoietic stem cells drive aging-associated immune remodeling. Blood 132:565–576PubMedPubMedCentral Leins H, Mulaw M, Eiwen K et al (2018) Aged murine hematopoietic stem cells drive aging-associated immune remodeling. Blood 132:565–576PubMedPubMedCentral
95.
Zurück zum Zitat Larbi A, Franceschi C, Mazzatti D et al (2008) Aging of the immune system as a prognostic factor for humanlongevity. Physiology (Bethesda) 23:64–74PubMed Larbi A, Franceschi C, Mazzatti D et al (2008) Aging of the immune system as a prognostic factor for humanlongevity. Physiology (Bethesda) 23:64–74PubMed
96.
Zurück zum Zitat Prata LGPL, Ovsyannikova IG, Tchkonia T et al (2018) Senescent cell clearance by the immune system: Emerging therapeutic opportunities. Semin Immunol 40:101275PubMed Prata LGPL, Ovsyannikova IG, Tchkonia T et al (2018) Senescent cell clearance by the immune system: Emerging therapeutic opportunities. Semin Immunol 40:101275PubMed
97.
Zurück zum Zitat Yousefzadeh MJ, Flores RR, Zhu Y et al (2021) An aged immune system drives senescence and ageing of solid organs. Nature 594:100–105PubMedPubMedCentral Yousefzadeh MJ, Flores RR, Zhu Y et al (2021) An aged immune system drives senescence and ageing of solid organs. Nature 594:100–105PubMedPubMedCentral
99.
Zurück zum Zitat 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):625–634PubMedPubMedCentral 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):625–634PubMedPubMedCentral
100.
Zurück zum Zitat 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):4990PubMedPubMedCentral 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):4990PubMedPubMedCentral
Metadaten
Titel
Hautalterung – zelluläre Seneszenz
Wohin geht die Reise?
verfasst von
Prof. Dr. med. Karin Scharffetter-Kochanek
Yongfang Wang
Evgenia Makrantonaki
Diana Crisan
Meinhard Wlaschek
Hartmut Geiger
Pallab Maity
Publikationsdatum
28.08.2023
Verlag
Springer Medizin
Erschienen in
Die Dermatologie / Ausgabe 9/2023
Print ISSN: 2731-7005
Elektronische ISSN: 2731-7013
DOI
https://doi.org/10.1007/s00105-023-05201-x

Weitere Artikel der Ausgabe 9/2023

Die Dermatologie 9/2023 Zur Ausgabe

Leitlinien kompakt für die Dermatologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Hirsutismus bei PCOS: Laser- und Lichttherapien helfen

26.04.2024 Hirsutismus Nachrichten

Laser- und Lichtbehandlungen können bei Frauen mit polyzystischem Ovarialsyndrom (PCOS) den übermäßigen Haarwuchs verringern und das Wohlbefinden verbessern – bei alleiniger Anwendung oder in Kombination mit Medikamenten.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

22.04.2024 DGIM 2024 Nachrichten

Um Menschen nach der Flucht aus einem Krisengebiet bestmöglich medizinisch betreuen zu können, ist es gut zu wissen, welche Erkrankungen im jeweiligen Herkunftsland häufig sind. Dabei hilft eine Internetseite der CDC (Centers for Disease Control and Prevention).

Kein Abstrich bei chronischen Wunden ohne Entzündungszeichen!

16.04.2024 DGIM 2024 Nachrichten

Den Reflex, eine oberflächliche chronische Hautwunde ohne Entzündungszeichen in jedem Fall abzustreichen, sollte man nach einer neuen „Klug-entscheiden“-Empfehlung unterdrücken.

Update Dermatologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.