Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging.
To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged tissues in both male and female mice, and a similar phenomenon was observed in human tissues, suggesting the potential of the abnormal elevation of immunoglobulins as an evolutionarily conserved feature in aging. Furthermore, we observed that IgG could induce a pro-senescent state in macrophages and microglia, thereby exacerbating tissue aging, and that targeted reduction of IgG mitigated aging across various tissues in male mice. This study provides a high-resolution spatial depiction of aging and indicates the pivotal role of immunoglobulin-associated senescence during the aging process.
Pubmed ID: 39500323 RIS Download
Research resources used in this publication
None foundAdditional research tools detected in this publication
None foundAntibodies used in this publication
- beta-Actin (AC-15) (RRID:AB_1119529)
- Goat anti-Human IgG (Gamma chain) Cross-Adsorbed Secondary Antibody, HRP (RRID:AB_2533962)
- Phospho-NF-κB p65 (Ser536) (93H1) Rabbit mAb (RRID:AB_331284)
- F4/80 antibody [BM8] (RRID:AB_443548)
- 4 Hydroxynonenal antibody (RRID:AB_722490)
- Recombinant Anti-iNOS antibody [RM1017] (RRID:AB_3083470)
- IL-1beta (11E5) (RRID:AB_629741)
- Human IgG Antibody (RRID:AB_2918970)
- Mouse Anti-Human Syndecan Monoclonal Antibody, Unconjugated, Clone B-A38 (RRID:AB_778207)
- TNF alpha antibody [52B83] (RRID:AB_302615)
- F4/80 antibody [CI:A3-1] (RRID:AB_1140040)
- Recombinant Anti-p21 antibody [EPR18021] (RRID:AB_2734729)
- Anti-CD3 antibody (RRID:AB_305055)
- Mouse E-Cadherin Affinity Purified Polyclonal Ab (RRID:AB_355568)
- F4/80 antibody [F4/80] (RRID:AB_10712189)
- Anti -F4/80 Rabbit pAb (RRID:AB_2938980)
- CYP11A1 Polyclonal Antibody (RRID:AB_2763764)
- CD79B (D7V2F) Rabbit mAb (RRID:AB_2800254)
- Rabbit Anti-Mouse IgG H&L (RRID:AB_2614925)
- Iba1 antibody (RRID:AB_2224402)
- Goat Anti-Mouse Kappa-BIOT (RRID:AB_2794383)
- Anti-NeuN antibody [EPR12763] (RRID:AB_2532109)
- CD45 antibody (RRID:AB_442810)
- Rabbit Anti-Glutamine Synthetase Polyclonal Antibody, Unconjugated (RRID:AB_880241)
- Mouse IL-6 ELISA Ready-SET-Go!¨ 2 x 96 tests Kit (RRID:AB_2574986)
- Mouse IgG ELISA Kit (RRID:AB_2892028)
- Donkey anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 568 (RRID:AB_11180865)
- Donkey anti-Rat IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (RRID:AB_2535794)
- Alexa Fluor(R) 488 anti-mouse MAdCAM-1 (RRID:AB_493398)
- Donkey anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (RRID:AB_141607)
- Normal Donkey Serum (RRID:AB_2337258)
- Donkey anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 568 (RRID:AB_2534017)
- Donkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (RRID:AB_2534102)
- Donkey Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor ?? 488 Conjugated (RRID:AB_2535792)
- Donkey anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 647 (RRID:AB_2536183)
- Donkey anti-Goat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 568 (RRID:AB_2534104)
- Recombinant Anti-CD68 antibody [EPR20545] (RRID:AB_2801637)
- Mouse Anti-CD68 Monoclonal Antibody, Unconjugated, Clone KP1 (RRID:AB_307338)
- Anti-human Endogenous Retrovirus type K (HERV K) envelope protein. monoclonal antibody (RRID:AB_10891119)
- Stat1 Antibody (RRID:AB_2198300)
- H3K9me3-human,H3K9me3-mouse (RRID:AB_306848)
- Horseradish enzyme labeled goat anti-rabbit IgG (H+L) (affinity purification) (RRID:AB_2747412)
- Horseradish enzyme labeled goat anti-mouse IgG (H+L) (affinity purification) (RRID:AB_2747415)
- Phospho-Histone H2A.X (Ser139) (20E3) Rabbit mAb (RRID:AB_2118009)
- Anti-Lamin B1 antibody - Nuclear Envelope Marker (RRID:AB_443298)
- MMTV Antibody (RRID:AB_3307963)
Associated grants
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This is a list of tools and resources that we have found mentioned in this publication.
beta-Actin (AC-15) (antibody)
RRID:AB_1119529
This monoclonal targets beta-Actin (AC-15)
View all literature mentionsGoat anti-Human IgG (Gamma chain) Cross-Adsorbed Secondary Antibody, HRP (antibody)
RRID:AB_2533962
This polyclonal secondary targets IgG (Gamma chain)
View all literature mentionsPhospho-NF-κB p65 (Ser536) (93H1) Rabbit mAb (antibody)
RRID:AB_331284
This monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsF4/80 antibody [BM8] (antibody)
RRID:AB_443548
This monoclonal targets F4/80 antibody [BM8]
View all literature mentions4 Hydroxynonenal antibody (antibody)
RRID:AB_722490
This polyclonal targets 4 Hydroxynonenal antibody
View all literature mentionsRecombinant Anti-iNOS antibody [RM1017] (antibody)
RRID:AB_3083470
This recombinant monoclonal targets iNOS
View all literature mentionsIL-1beta (11E5) (antibody)
RRID:AB_629741
This monoclonal targets IL-1beta (11E5)
View all literature mentionsHuman IgG Antibody (antibody)
RRID:AB_2918970
This polyclonal targets Human IgG
View all literature mentionsMouse Anti-Human Syndecan Monoclonal Antibody, Unconjugated, Clone B-A38 (antibody)
RRID:AB_778207
This monoclonal targets Human Syndecan
View all literature mentionsTNF alpha antibody [52B83] (antibody)
RRID:AB_302615
This monoclonal targets TNF alpha antibody [52B83]
View all literature mentionsF4/80 antibody [CI:A3-1] (antibody)
RRID:AB_1140040
This monoclonal targets F4/80 antibody [CI:A3-1]
View all literature mentionsRecombinant Anti-p21 antibody [EPR18021] (antibody)
RRID:AB_2734729
This recombinant targets p21
View all literature mentionsAnti-CD3 antibody (antibody)
RRID:AB_305055
This polyclonal targets CD3
View all literature mentionsMouse E-Cadherin Affinity Purified Polyclonal Ab (antibody)
RRID:AB_355568
This polyclonal targets Mouse E-Cadherin Affinity Purified Ab
View all literature mentionsF4/80 antibody [F4/80] (antibody)
RRID:AB_10712189
This monoclonal targets F4/80 antibody [F4/80]
View all literature mentionsAnti -F4/80 Rabbit pAb (antibody)
RRID:AB_2938980
This polyclonal targets F4/80
View all literature mentionsCYP11A1 Polyclonal Antibody (antibody)
RRID:AB_2763764
This polyclonal targets CYP11A1
View all literature mentionsCD79B (D7V2F) Rabbit mAb (antibody)
RRID:AB_2800254
This monoclonal targets Ig-beta
View all literature mentionsRabbit Anti-Mouse IgG H&L (antibody)
RRID:AB_2614925
This polyclonal secondary targets IgG H&L
View all literature mentionsGoat Anti-Mouse Kappa-BIOT (antibody)
RRID:AB_2794383
This unknown targets Kappa
View all literature mentionsAnti-NeuN antibody [EPR12763] (antibody)
RRID:AB_2532109
This monoclonal targets NeuN
View all literature mentionsCD45 antibody (antibody)
RRID:AB_442810
This polyclonal targets CD45 antibody
View all literature mentionsRabbit Anti-Glutamine Synthetase Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_880241
This polyclonal targets Glutamine Synthetase
View all literature mentionsMouse IL-6 ELISA Ready-SET-Go!¨ 2 x 96 tests Kit (antibody)
RRID:AB_2574986
This unknown targets IL-6
View all literature mentionsMouse IgG ELISA Kit (antibody)
RRID:AB_2892028
This unknown targets IgG
View all literature mentionsDonkey anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 568 (antibody)
RRID:AB_11180865
This polyclonal secondary targets Mouse IgG (H+L)
View all literature mentionsDonkey anti-Rat IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (antibody)
RRID:AB_2535794
This polyclonal secondary targets IgG (H+L)
View all literature mentionsAlexa Fluor(R) 488 anti-mouse MAdCAM-1 (antibody)
RRID:AB_493398
This monoclonal targets MAdCAM-1
View all literature mentionsDonkey anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 488 (antibody)
RRID:AB_141607
This polyclonal secondary targets IgG (H+L)
View all literature mentionsNormal Donkey Serum (antibody)
RRID:AB_2337258
This unknown targets Donkey Serum
View all literature mentionsDonkey anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 568 (antibody)
RRID:AB_2534017
This polyclonal secondary targets IgG (H+L)
View all literature mentionsDonkey Anti-Goat IgG (H+L) Antibody, Alexa Fluor 488 Conjugated (antibody)
RRID:AB_2534102
This unknown targets IgG (H+L)
View all literature mentionsDonkey Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor ?? 488 Conjugated (antibody)
RRID:AB_2535792
This unknown targets Rabbit IgG (H+L)
View all literature mentionsDonkey anti-Rabbit IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 647 (antibody)
RRID:AB_2536183
This polyclonal secondary targets IgG (H+L)
View all literature mentionsDonkey anti-Goat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 568 (antibody)
RRID:AB_2534104
This polyclonal secondary targets IgG (H+L)
View all literature mentionsRecombinant Anti-CD68 antibody [EPR20545] (antibody)
RRID:AB_2801637
This monoclonal targets CD68
View all literature mentionsMouse Anti-CD68 Monoclonal Antibody, Unconjugated, Clone KP1 (antibody)
RRID:AB_307338
This monoclonal targets CD68
View all literature mentionsAnti-human Endogenous Retrovirus type K (HERV K) envelope protein. monoclonal antibody (antibody)
RRID:AB_10891119
This unknown targets human Endogenous Retrovirus type K (HERV K) envelope protein. monoclonal antibody
View all literature mentionsH3K9me3-human,H3K9me3-mouse (antibody)
RRID:AB_306848
This polyclonal targets H3K9me3
View all literature mentionsHorseradish enzyme labeled goat anti-rabbit IgG (H+L) (affinity purification) (antibody)
RRID:AB_2747412
This polyclonal secondary targets IgG (H+L)
View all literature mentionsHorseradish enzyme labeled goat anti-mouse IgG (H+L) (affinity purification) (antibody)
RRID:AB_2747415
This polyclonal secondary targets IgG (H+L)
View all literature mentionsPhospho-Histone H2A.X (Ser139) (20E3) Rabbit mAb (antibody)
RRID:AB_2118009
This monoclonal targets Histone H2A.X, phospho (Ser139)
View all literature mentionsAnti-Lamin B1 antibody - Nuclear Envelope Marker (antibody)
RRID:AB_443298
This polyclonal targets LMNB1
View all literature mentions
