Mitochondrial peptides modulate mitochondrial function during cellular senescence
Cellular senescence is a complex cell fate response that is thought to underlie several age-related pathologies. Despite a loss of proliferative potential, senescent cells are metabolically active and produce energy-consuming effectors, including senescence-associated secretory phenotypes (SASPs). M...
Uloženo v:
| Vydáno v: | Aging (Albany, NY.) Ročník 10; číslo 6; s. 1239 |
|---|---|
| Hlavní autoři: | , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
10.06.2018
|
| Témata: | |
| ISSN: | 1945-4589, 1945-4589 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | Cellular senescence is a complex cell fate response that is thought to underlie several age-related pathologies. Despite a loss of proliferative potential, senescent cells are metabolically active and produce energy-consuming effectors, including senescence-associated secretory phenotypes (SASPs). Mitochondria play crucial roles in energy production and cellular signaling, but the key features of mitochondrial physiology and particularly of mitochondria-derived peptides (MDPs), remain underexplored in senescence responses. Here, we used primary human fibroblasts made senescent by replicative exhaustion, doxorubicin or hydrogen peroxide treatment, and examined the number of mitochondria and the levels of mitochondrial respiration, mitochondrial DNA methylation and the mitochondria-encoded peptides humanin, MOTS-c, SHLP2 and SHLP6. Senescent cells showed increased numbers of mitochondria and higher levels of mitochondrial respiration, variable changes in mitochondrial DNA methylation, and elevated levels of humanin and MOTS-c. Humanin and MOTS-c administration modestly increased mitochondrial respiration and selected components of the SASP in doxorubicin-induced senescent cells partially via JAK pathway. Targeting metabolism in senescence cells is an important strategy to reduce SASP production for eliminating the deleterious effects of senescence. These results provide insight into the role of MDPs in mitochondrial energetics and the production of SASP components by senescent cells. |
|---|---|
| AbstractList | Cellular senescence is a complex cell fate response that is thought to underlie several age-related pathologies. Despite a loss of proliferative potential, senescent cells are metabolically active and produce energy-consuming effectors, including senescence-associated secretory phenotypes (SASPs). Mitochondria play crucial roles in energy production and cellular signaling, but the key features of mitochondrial physiology and particularly of mitochondria-derived peptides (MDPs), remain underexplored in senescence responses. Here, we used primary human fibroblasts made senescent by replicative exhaustion, doxorubicin or hydrogen peroxide treatment, and examined the number of mitochondria and the levels of mitochondrial respiration, mitochondrial DNA methylation and the mitochondria-encoded peptides humanin, MOTS-c, SHLP2 and SHLP6. Senescent cells showed increased numbers of mitochondria and higher levels of mitochondrial respiration, variable changes in mitochondrial DNA methylation, and elevated levels of humanin and MOTS-c. Humanin and MOTS-c administration modestly increased mitochondrial respiration and selected components of the SASP in doxorubicin-induced senescent cells partially via JAK pathway. Targeting metabolism in senescence cells is an important strategy to reduce SASP production for eliminating the deleterious effects of senescence. These results provide insight into the role of MDPs in mitochondrial energetics and the production of SASP components by senescent cells. Cellular senescence is a complex cell fate response that is thought to underlie several age-related pathologies. Despite a loss of proliferative potential, senescent cells are metabolically active and produce energy-consuming effectors, including senescence-associated secretory phenotypes (SASPs). Mitochondria play crucial roles in energy production and cellular signaling, but the key features of mitochondrial physiology and particularly of mitochondria-derived peptides (MDPs), remain underexplored in senescence responses. Here, we used primary human fibroblasts made senescent by replicative exhaustion, doxorubicin or hydrogen peroxide treatment, and examined the number of mitochondria and the levels of mitochondrial respiration, mitochondrial DNA methylation and the mitochondria-encoded peptides humanin, MOTS-c, SHLP2 and SHLP6. Senescent cells showed increased numbers of mitochondria and higher levels of mitochondrial respiration, variable changes in mitochondrial DNA methylation, and elevated levels of humanin and MOTS-c. Humanin and MOTS-c administration modestly increased mitochondrial respiration and selected components of the SASP in doxorubicin-induced senescent cells partially via JAK pathway. Targeting metabolism in senescence cells is an important strategy to reduce SASP production for eliminating the deleterious effects of senescence. These results provide insight into the role of MDPs in mitochondrial energetics and the production of SASP components by senescent cells.Cellular senescence is a complex cell fate response that is thought to underlie several age-related pathologies. Despite a loss of proliferative potential, senescent cells are metabolically active and produce energy-consuming effectors, including senescence-associated secretory phenotypes (SASPs). Mitochondria play crucial roles in energy production and cellular signaling, but the key features of mitochondrial physiology and particularly of mitochondria-derived peptides (MDPs), remain underexplored in senescence responses. Here, we used primary human fibroblasts made senescent by replicative exhaustion, doxorubicin or hydrogen peroxide treatment, and examined the number of mitochondria and the levels of mitochondrial respiration, mitochondrial DNA methylation and the mitochondria-encoded peptides humanin, MOTS-c, SHLP2 and SHLP6. Senescent cells showed increased numbers of mitochondria and higher levels of mitochondrial respiration, variable changes in mitochondrial DNA methylation, and elevated levels of humanin and MOTS-c. Humanin and MOTS-c administration modestly increased mitochondrial respiration and selected components of the SASP in doxorubicin-induced senescent cells partially via JAK pathway. Targeting metabolism in senescence cells is an important strategy to reduce SASP production for eliminating the deleterious effects of senescence. These results provide insight into the role of MDPs in mitochondrial energetics and the production of SASP components by senescent cells. |
| Author | Kim, Su-Jeong Wan, Junxiang Mehta, Hemal H Hoffman, Andrew R Cohen, Pinchas Hu, Ji-Fan Chen, Jingcheng Kuehnemann, Chisaka |
| Author_xml | – sequence: 1 givenname: Su-Jeong surname: Kim fullname: Kim, Su-Jeong organization: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA – sequence: 2 givenname: Hemal H surname: Mehta fullname: Mehta, Hemal H organization: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA – sequence: 3 givenname: Junxiang surname: Wan fullname: Wan, Junxiang organization: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA – sequence: 4 givenname: Chisaka surname: Kuehnemann fullname: Kuehnemann, Chisaka organization: Buck Institute for Research on Aging, Novato, CA 94945, USA – sequence: 5 givenname: Jingcheng surname: Chen fullname: Chen, Jingcheng organization: Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304, USA – sequence: 6 givenname: Ji-Fan surname: Hu fullname: Hu, Ji-Fan organization: Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304, USA – sequence: 7 givenname: Andrew R surname: Hoffman fullname: Hoffman, Andrew R organization: Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA 94304, USA – sequence: 8 givenname: Pinchas surname: Cohen fullname: Cohen, Pinchas organization: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29886458$$D View this record in MEDLINE/PubMed |
| BookMark | eNpVkEtLxDAUhYOMOA9dupUu3XTMO81SBh8DM4ig65Imt2OkTWrTLvz3VhxBV-fA-bj3cJZoFmIAhC4JXpNCMnpjDj4c1gQTLtkJWhDNRc5FoWd__BwtU3rHWArB5RmaU10UcgoW6Hnvh2jfYnC9N03WQTd4BylroxsbM0DW_svrMdjBx5C5sZ_eZhaaZuL6LEGAZCFYOEentWkSXBx1hV7v7142j_nu6WG7ud3llhVqyKlhrNJAJcbKYctZRbUVkiuOqVCkcgUHQmuGjWBKEs2crrCW2lUUT76mK3T9c7fr48cIaShbn777mABxTCXFglFFtOITenVEx6oFV3a9b03_Wf7OQL8A5J1hhA |
| CitedBy_id | crossref_primary_10_1155_2020_2583601 crossref_primary_10_4093_dmj_2022_0333 crossref_primary_10_3389_fonc_2022_832804 crossref_primary_10_1016_j_freeradbiomed_2024_12_038 crossref_primary_10_3389_fendo_2023_1120533 crossref_primary_10_3390_biom10060957 crossref_primary_10_1002_j_2040_4603_2021_tb00159_x crossref_primary_10_1089_rej_2018_2114 crossref_primary_10_1016_j_acvd_2021_10_013 crossref_primary_10_1038_s42003_020_01322_4 crossref_primary_10_3389_fphys_2022_772313 crossref_primary_10_1016_j_biopha_2023_114616 crossref_primary_10_1002_bies_201900046 crossref_primary_10_1016_j_acvd_2020_03_020 crossref_primary_10_1016_j_cellsig_2023_110794 crossref_primary_10_2147_DMSO_S306026 crossref_primary_10_1002_mnfr_202200003 crossref_primary_10_1177_09603271221136208 crossref_primary_10_1016_j_omtn_2020_09_040 crossref_primary_10_3390_nu15071627 crossref_primary_10_3390_cells13151281 crossref_primary_10_3390_biology12040558 crossref_primary_10_3390_ijms23031517 crossref_primary_10_3390_ijms22168770 crossref_primary_10_1016_j_prp_2025_156115 crossref_primary_10_1007_s11306_019_1549_7 crossref_primary_10_1016_j_peptides_2020_170399 crossref_primary_10_36660_abc_20220358 crossref_primary_10_1016_j_bbadis_2020_166016 crossref_primary_10_1016_j_peptides_2023_171147 crossref_primary_10_1007_s10142_024_01426_8 crossref_primary_10_1016_j_exer_2021_108918 crossref_primary_10_1016_j_ejcb_2023_151289 crossref_primary_10_1111_febs_16361 crossref_primary_10_3389_fgene_2020_00095 crossref_primary_10_1002_1873_3468_13498 crossref_primary_10_1007_s00281_020_00813_0 crossref_primary_10_1093_lifemedi_lnaf019 crossref_primary_10_3390_metabo13010125 crossref_primary_10_1111_acel_70179 crossref_primary_10_1016_j_exger_2022_111866 crossref_primary_10_3390_antiox13050613 crossref_primary_10_3390_genes12050756 crossref_primary_10_1016_j_mad_2022_111706 crossref_primary_10_1242_dev_175786 crossref_primary_10_3389_fphar_2022_1059434 crossref_primary_10_1007_s11033_020_05429_z crossref_primary_10_1038_s41598_019_42064_6 crossref_primary_10_1007_s12975_021_00945_x crossref_primary_10_3390_biom12030427 crossref_primary_10_1007_s00109_019_01758_0 crossref_primary_10_1091_mbc_E21_05_0262 crossref_primary_10_1172_JCI158449 crossref_primary_10_1016_j_yexcr_2020_111997 crossref_primary_10_1200_JCO_24_00608 crossref_primary_10_1007_s10989_023_10558_7 crossref_primary_10_34067_KID_0000000000000316 crossref_primary_10_1172_JCI158447 crossref_primary_10_33678_cor_2022_057 crossref_primary_10_1016_j_arr_2024_102275 crossref_primary_10_1007_s12035_023_03443_3 crossref_primary_10_1007_s11357_020_00262_5 crossref_primary_10_1007_s43188_023_00208_x crossref_primary_10_1080_14728222_2019_1559300 crossref_primary_10_1186_s13690_019_0375_8 crossref_primary_10_1165_rcmb_2018_0328OC crossref_primary_10_1016_j_lfs_2023_121666 crossref_primary_10_2147_DDDT_S460265 crossref_primary_10_3390_cells9051102 crossref_primary_10_1002_jbt_23246 crossref_primary_10_3389_fphys_2025_1602271 crossref_primary_10_3390_ijms20184439 crossref_primary_10_3390_jdb12010009 crossref_primary_10_1007_s00018_024_05230_2 crossref_primary_10_1016_j_canlet_2020_10_038 crossref_primary_10_1038_s41598_023_47073_0 crossref_primary_10_1152_ajprenal_00202_2019 crossref_primary_10_1007_s00439_020_02119_5 crossref_primary_10_1016_j_bbagen_2021_130066 crossref_primary_10_1152_japplphysiol_00032_2020 crossref_primary_10_1007_s11357_025_01679_6 crossref_primary_10_1016_j_tma_2019_12_003 crossref_primary_10_1038_s12276_025_01521_1 crossref_primary_10_1016_j_freeradbiomed_2021_05_003 crossref_primary_10_1111_joim_13012 crossref_primary_10_1038_s41598_020_79552_z crossref_primary_10_1007_s00441_019_03049_z crossref_primary_10_3389_fphys_2021_734976 crossref_primary_10_1016_j_redox_2020_101568 crossref_primary_10_2174_0118715257368076250324041741 crossref_primary_10_1038_s41594_022_00790_y crossref_primary_10_1016_j_yexcr_2020_112056 crossref_primary_10_1016_j_mito_2023_06_002 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.18632/aging.101463 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine Biology |
| EISSN | 1945-4589 |
| ExternalDocumentID | 29886458 |
| Genre | Journal Article |
| GrantInformation_xml | – fundername: NIA NIH HHS grantid: P01 AG034906 – fundername: NIA NIH HHS grantid: P01 AG055369 – fundername: NIA NIH HHS grantid: RF1 AG061834 |
| GroupedDBID | --- 53G ADBBV ADRAZ ALMA_UNASSIGNED_HOLDINGS AOIJS BAWUL CGR CUY CVF DIK E3Z ECM EIF FRP GX1 HYE KQ8 M48 NPM O5R O5S OK1 PGMZT RPM W2D 7X8 |
| ID | FETCH-LOGICAL-c387t-2a33b9e26007d0c43b29c5647402571bd84e12f30a5376193d9b0969db203d9f2 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 110 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000437446300009&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1945-4589 |
| IngestDate | Thu Jul 10 17:22:02 EDT 2025 Thu Jan 02 22:39:09 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | false |
| IsScholarly | true |
| Issue | 6 |
| Keywords | senescence SASP (senescence-associated secretory phenotype) mitochondrial energetics mitochondrial-derived peptides mitochondria mtDNA methylation |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c387t-2a33b9e26007d0c43b29c5647402571bd84e12f30a5376193d9b0969db203d9f2 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | http://europepmc.org/pmc/articles/PMC6046248 |
| PMID | 29886458 |
| PQID | 2053271974 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2053271974 pubmed_primary_29886458 |
| PublicationCentury | 2000 |
| PublicationDate | 20180610 |
| PublicationDateYYYYMMDD | 2018-06-10 |
| PublicationDate_xml | – month: 6 year: 2018 text: 20180610 day: 10 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Aging (Albany, NY.) |
| PublicationTitleAlternate | Aging (Albany NY) |
| PublicationYear | 2018 |
| SSID | ssj0065546 |
| Score | 2.5131147 |
| Snippet | Cellular senescence is a complex cell fate response that is thought to underlie several age-related pathologies. Despite a loss of proliferative potential,... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 1239 |
| SubjectTerms | Carbamates - metabolism Cells, Cultured Cellular Senescence - physiology DNA Copy Number Variations DNA, Mitochondrial - genetics Fibroblasts Gene Expression Regulation - physiology Humans Mitochondria - metabolism Mitochondrial Proteins - genetics Mitochondrial Proteins - metabolism Sulfonamides - metabolism |
| Title | Mitochondrial peptides modulate mitochondrial function during cellular senescence |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/29886458 https://www.proquest.com/docview/2053271974 |
| Volume | 10 |
| WOSCitedRecordID | wos000437446300009&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8QwEA7qqnjx_VhfRPAabJM0j5OIuHhwlxVU9rakTQoetl3tKvjvnWm7igdB8FIKISEkk5lvJpP5CDlHDBBZp1kuRMakUoE5mScMLKHTXnipatK-pzs9GJjRyA7bgFvVplXOdWKtqH2ZYYwcnPREcB0D_L2cvjBkjcLb1ZZCY5F0BEAZlGo9-rpFUEnzUAf89ITJxNi2xqZRgl_UHEDou0qsAPobuqytTG_jv_PbJOstvqRXjUBskYVQbJOVhnHyY5us9tu79B1y34fDDMqv8CiDdIrpLT5UdFJ6pPQKdPKjHQ0gbiJtHjZSjPhjCiutUFtmqCB2yWPv5uH6lrUECywTRs8Yd0KkNtQ16n2USZFymyVKanAqEx2n3sgQ81xEDou-ANTzNgWXx_qUR_Cf8z2yVJRFOCA0uBz2WGloEjI1Ks2lg46AXiSHcZMuOZsv2xgEGOfoilC-VePvheuS_Wbtx9Om0saYW2MU7NzhH3ofkTUAMwbTuOLomHRyOL7hhCxn77Pn6vW0lgz4Dob9T0WGww0 |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Mitochondrial+peptides+modulate+mitochondrial+function+during+cellular+senescence&rft.jtitle=Aging+%28Albany%2C+NY.%29&rft.au=Kim%2C+Su-Jeong&rft.au=Mehta%2C+Hemal+H&rft.au=Wan%2C+Junxiang&rft.au=Kuehnemann%2C+Chisaka&rft.date=2018-06-10&rft.eissn=1945-4589&rft.volume=10&rft.issue=6&rft.spage=1239&rft_id=info:doi/10.18632%2Faging.101463&rft_id=info%3Apmid%2F29886458&rft_id=info%3Apmid%2F29886458&rft.externalDocID=29886458 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1945-4589&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1945-4589&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1945-4589&client=summon |