Human umbilical cord plasma proteins revitalize hippocampal function in aged mice
Joseph M Castellano, Kira I Mosher, Rachelle J Abbey, Alisha A McBride, Michelle L James, Daniela Berdnik, Jadon C Shen, Bende Zou, Xinmin S Xie, Martha Tingle, Izumi V Hinkson, Martin S Angst, Tony Wyss-Coray, Joseph M Castellano, Kira I Mosher, Rachelle J Abbey, Alisha A McBride, Michelle L James, Daniela Berdnik, Jadon C Shen, Bende Zou, Xinmin S Xie, Martha Tingle, Izumi V Hinkson, Martin S Angst, Tony Wyss-Coray
Abstract
Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation, an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation and downregulated in the aged brain. In addition to revitalizing other aged tissues, exposure to factors in young blood counteracts age-related changes in these central nervous system parameters, although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown. We hypothesized that plasma of an early developmental stage, namely umbilical cord plasma, provides a reservoir of such plasticity-promoting proteins. Here we show that human cord plasma treatment revitalizes the hippocampus and improves cognitive function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and young mouse hippocampi, appears in the brain after systemic administration and increases synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion experiments in aged mice revealed TIMP2 to be necessary for the cognitive benefits conferred by cord plasma. We find that systemic pools of TIMP2 are necessary for spatial memory in young mice, while treatment of brain slices with TIMP2 antibody prevents long-term potentiation, arguing for previously unknown roles for TIMP2 in normal hippocampal function. Our findings reveal that human cord plasma contains plasticity-enhancing proteins of high translational value for targeting ageing- or disease-associated hippocampal dysfunction.
Conflict of interest statement
Competing financial interests
T.W.-C. is co-founder of Alkahest, Inc. T.W.-C., J.M.C., M.S.A. are Alkahest shareholders. Stanford filed patent applications covering a method treating aging-associated conditions by young plasma (PCT/US2014/068897; co-inventors: T.W.-C., J.M.C., M.S.A.) or TIMP2 (PCT/US2016/036032; co-inventors: T.W.-C., J.M.C.).
Figures
![Extended Data Figure 1. Expression of common…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f5.jpg)
Extended Data Figure 2. Immunodeficient NSG mice…
Extended Data Figure 2. Immunodeficient NSG mice exhibit age-dependent hippocampal dysfunction independent of sensory function
Extended Data Figure 3. Human cord plasma…
Extended Data Figure 3. Human cord plasma treatment enhances c-Fos expression in the dentate gyrus…
Extended Data Figure 4. Most c-Fos-expressing cells…
Extended Data Figure 4. Most c-Fos-expressing cells activated by cord plasma in dentate gyrus are…
Extended Data Figure 5. Cord, but not…
Extended Data Figure 5. Cord, but not young or elderly plasma, affects LTP in aged…
Extended Data Figure 6. Systemic treatment with…
Extended Data Figure 6. Systemic treatment with CSF2 improves learning and memory in aged mice
Extended Data Figure 7. TIMP2 decreases early…
Extended Data Figure 7. TIMP2 decreases early in plasma and hippocampus and enters the CNS…
Extended Data Figure 8. Effect of systemic…
Extended Data Figure 8. Effect of systemic TIMP2 treatment or whole-body TIMP2 deletion on dentate…
Extended Data Figure 9. Systemic TIMP2 neutralization…
Extended Data Figure 9. Systemic TIMP2 neutralization alters spatial memory but not activity or general…
Extended Data Figure 10. TIMP2 is critical…
Extended Data Figure 10. TIMP2 is critical for several cognitive benefits of cord plasma independent…
Figure 1. Human cord plasma enhances plasticity…
Figure 1. Human cord plasma enhances plasticity in the aged brain
Figure 2. Cord plasma improves neuronal function…
Figure 2. Cord plasma improves neuronal function within aged hippocampus
Figure 3. Protein microarray analysis identifies putative…
Figure 3. Protein microarray analysis identifies putative pro-plasticity factors
Figure 4. Systemic TIMP2 treatment improves neuronal…
Figure 4. Systemic TIMP2 treatment improves neuronal function within aged hippocampus and is critical for…
- Ageing: Are the secrets of healthy ageing within 'young blood'?Morris A. Morris A. Nat Rev Endocrinol. 2017 Jul;13(7):376. doi: 10.1038/nrendo.2017.60. Epub 2017 May 5. Nat Rev Endocrinol. 2017. PMID: 28474688 No abstract available.
- Brain ageing: A youthful reminder.Yates D. Yates D. Nat Rev Neurosci. 2017 Jun;18(6):322-323. doi: 10.1038/nrn.2017.59. Epub 2017 May 11. Nat Rev Neurosci. 2017. PMID: 28490778 No abstract available.
- Ageing: A youthful reminder.Yates D. Yates D. Nat Rev Drug Discov. 2017 May 31;16(6):384-385. doi: 10.1038/nrd.2017.112. Nat Rev Drug Discov. 2017. PMID: 28559551 No abstract available.
- Ageing: Rejuvenation study stirs old memories.Krischel M, Hansson N. Krischel M, et al. Nature. 2017 May 31;546(7656):33. doi: 10.1038/546033e. Nature. 2017. PMID: 28569802 No abstract available.
- Long-term enzyme replacement therapy improves neurocognitive functioning and hippocampal synaptic plasticity in immune-tolerant alpha-mannosidosis mice.Stroobants S, Damme M, Van der Jeugd A, Vermaercke B, Andersson C, Fogh J, Saftig P, Blanz J, D'Hooge R. Stroobants S, et al. Neurobiol Dis. 2017 Oct;106:255-268. doi: 10.1016/j.nbd.2017.07.013. Epub 2017 Jul 15. Neurobiol Dis. 2017. PMID: 28720484
- Structure-function-behavior relationship in estrogen-induced synaptic plasticity.Vierk R, Bayer J, Freitag S, Muhia M, Kutsche K, Wolbers T, Kneussel M, Sommer T, Rune GM. Vierk R, et al. Horm Behav. 2015 Aug;74:139-48. doi: 10.1016/j.yhbeh.2015.05.008. Epub 2015 May 24. Horm Behav. 2015. PMID: 26012713
- Tripchlorolide improves age-associated cognitive deficits by reversing hippocampal synaptic plasticity impairment and NMDA receptor dysfunction in SAMP8 mice.Lin N, Pan XD, Chen AQ, Zhu YG, Wu M, Zhang J, Chen XC. Lin N, et al. Behav Brain Res. 2014 Jan 1;258:8-18. doi: 10.1016/j.bbr.2013.10.010. Epub 2013 Oct 17. Behav Brain Res. 2014. PMID: 24140565
- Ageing, hippocampal synaptic activity and magnesium.Billard JM. Billard JM. Magnes Res. 2006 Sep;19(3):199-215. Magnes Res. 2006. PMID: 17172010 Review.
- Ovarian hormones, aging and stress on hippocampal synaptic plasticity.Foy MR. Foy MR. Neurobiol Learn Mem. 2011 Feb;95(2):134-44. doi: 10.1016/j.nlm.2010.11.003. Epub 2010 Nov 23. Neurobiol Learn Mem. 2011. PMID: 21081173 Free PMC article. Review.
- Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases.Ji S, Xiong M, Chen H, Liu Y, Zhou L, Hong Y, Wang M, Wang C, Fu X, Sun X. Ji S, et al. Signal Transduct Target Ther. 2023 Mar 14;8(1):116. doi: 10.1038/s41392-023-01343-5. Signal Transduct Target Ther. 2023. PMID: 36918530 Free PMC article. Review.
- Markers of aging: Unsupervised integrated analyses of the human plasma proteome.Coenen L, Lehallier B, de Vries HE, Middeldorp J. Coenen L, et al. Front Aging. 2023 Feb 22;4:1112109. doi: 10.3389/fragi.2023.1112109. eCollection 2023. Front Aging. 2023. PMID: 36911498 Free PMC article.
- Limited Proteolysis-Mass Spectrometry Reveals Aging-Associated Changes in Cerebrospinal Fluid Protein Abundances and Structures.Shuken SR, Rutledge J, Iram T, Losada PM, Wilson EN, Andreasson KI, Leib RD, Wyss-Coray T. Shuken SR, et al. Nat Aging. 2022 May;2(5):379-388. doi: 10.1038/s43587-022-00196-x. Epub 2022 Apr 11. Nat Aging. 2022. PMID: 36741774 Free PMC article.
- Blood-to-brain communication in aging and rejuvenation.Bieri G, Schroer AB, Villeda SA. Bieri G, et al. Nat Neurosci. 2023 Mar;26(3):379-393. doi: 10.1038/s41593-022-01238-8. Epub 2023 Jan 16. Nat Neurosci. 2023. PMID: 36646876 Review.
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Costanzo L, Soto B, Meier R, Geraghty P. Costanzo L, et al. Pulm Med. 2022 Dec 31;2022:3632764. doi: 10.1155/2022/3632764. eCollection 2022. Pulm Med. 2022. PMID: 36624735 Free PMC article. Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
- Aging / drug effects
- Aging / metabolism*
- Animals
- Blood Proteins / administration & dosage
- Blood Proteins / metabolism
- Blood Proteins / pharmacology*
- Cognition / drug effects
- Cognition / physiology
- Female
- Fetal Blood / chemistry*
- Hippocampus / cytology
- Hippocampus / drug effects*
- Hippocampus / physiology*
- Humans
- Long-Term Potentiation / drug effects
- Male
- Maze Learning / drug effects
- Maze Learning / physiology
- Mice
- Neuronal Plasticity / drug effects*
- Neuronal Plasticity / physiology
- Neurons / drug effects
- Neurons / physiology
- Protein Array Analysis
- Spatial Memory / drug effects
- Spatial Memory / physiology
- Tissue Inhibitor of Metalloproteinase-2 / administration & dosage
- Tissue Inhibitor of Metalloproteinase-2 / antagonists & inhibitors
- Tissue Inhibitor of Metalloproteinase-2 / metabolism
- Tissue Inhibitor of Metalloproteinase-2 / pharmacology
- Blood Proteins
- TIMP2 protein, human
- Tissue Inhibitor of Metalloproteinase-2
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Extended Data Figure 2. Immunodeficient NSG mice…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f6.jpg)
Extended Data Figure 3. Human cord plasma…
Extended Data Figure 3. Human cord plasma treatment enhances c-Fos expression in the dentate gyrus…
Extended Data Figure 4. Most c-Fos-expressing cells…
Extended Data Figure 4. Most c-Fos-expressing cells activated by cord plasma in dentate gyrus are…
Extended Data Figure 5. Cord, but not…
Extended Data Figure 5. Cord, but not young or elderly plasma, affects LTP in aged…
Extended Data Figure 6. Systemic treatment with…
Extended Data Figure 6. Systemic treatment with CSF2 improves learning and memory in aged mice
Extended Data Figure 7. TIMP2 decreases early…
Extended Data Figure 7. TIMP2 decreases early in plasma and hippocampus and enters the CNS…
Extended Data Figure 8. Effect of systemic…
Extended Data Figure 8. Effect of systemic TIMP2 treatment or whole-body TIMP2 deletion on dentate…
Extended Data Figure 9. Systemic TIMP2 neutralization…
Extended Data Figure 9. Systemic TIMP2 neutralization alters spatial memory but not activity or general…
Extended Data Figure 10. TIMP2 is critical…
Extended Data Figure 10. TIMP2 is critical for several cognitive benefits of cord plasma independent…
Figure 1. Human cord plasma enhances plasticity…
Figure 1. Human cord plasma enhances plasticity in the aged brain
Figure 2. Cord plasma improves neuronal function…
Figure 2. Cord plasma improves neuronal function within aged hippocampus
Figure 3. Protein microarray analysis identifies putative…
Figure 3. Protein microarray analysis identifies putative pro-plasticity factors
Figure 4. Systemic TIMP2 treatment improves neuronal…
Figure 4. Systemic TIMP2 treatment improves neuronal function within aged hippocampus and is critical for…
- Ageing: Are the secrets of healthy ageing within 'young blood'?Morris A. Morris A. Nat Rev Endocrinol. 2017 Jul;13(7):376. doi: 10.1038/nrendo.2017.60. Epub 2017 May 5. Nat Rev Endocrinol. 2017. PMID: 28474688 No abstract available.
- Brain ageing: A youthful reminder.Yates D. Yates D. Nat Rev Neurosci. 2017 Jun;18(6):322-323. doi: 10.1038/nrn.2017.59. Epub 2017 May 11. Nat Rev Neurosci. 2017. PMID: 28490778 No abstract available.
- Ageing: A youthful reminder.Yates D. Yates D. Nat Rev Drug Discov. 2017 May 31;16(6):384-385. doi: 10.1038/nrd.2017.112. Nat Rev Drug Discov. 2017. PMID: 28559551 No abstract available.
- Ageing: Rejuvenation study stirs old memories.Krischel M, Hansson N. Krischel M, et al. Nature. 2017 May 31;546(7656):33. doi: 10.1038/546033e. Nature. 2017. PMID: 28569802 No abstract available.
- Long-term enzyme replacement therapy improves neurocognitive functioning and hippocampal synaptic plasticity in immune-tolerant alpha-mannosidosis mice.Stroobants S, Damme M, Van der Jeugd A, Vermaercke B, Andersson C, Fogh J, Saftig P, Blanz J, D'Hooge R. Stroobants S, et al. Neurobiol Dis. 2017 Oct;106:255-268. doi: 10.1016/j.nbd.2017.07.013. Epub 2017 Jul 15. Neurobiol Dis. 2017. PMID: 28720484
- Structure-function-behavior relationship in estrogen-induced synaptic plasticity.Vierk R, Bayer J, Freitag S, Muhia M, Kutsche K, Wolbers T, Kneussel M, Sommer T, Rune GM. Vierk R, et al. Horm Behav. 2015 Aug;74:139-48. doi: 10.1016/j.yhbeh.2015.05.008. Epub 2015 May 24. Horm Behav. 2015. PMID: 26012713
- Tripchlorolide improves age-associated cognitive deficits by reversing hippocampal synaptic plasticity impairment and NMDA receptor dysfunction in SAMP8 mice.Lin N, Pan XD, Chen AQ, Zhu YG, Wu M, Zhang J, Chen XC. Lin N, et al. Behav Brain Res. 2014 Jan 1;258:8-18. doi: 10.1016/j.bbr.2013.10.010. Epub 2013 Oct 17. Behav Brain Res. 2014. PMID: 24140565
- Ageing, hippocampal synaptic activity and magnesium.Billard JM. Billard JM. Magnes Res. 2006 Sep;19(3):199-215. Magnes Res. 2006. PMID: 17172010 Review.
- Ovarian hormones, aging and stress on hippocampal synaptic plasticity.Foy MR. Foy MR. Neurobiol Learn Mem. 2011 Feb;95(2):134-44. doi: 10.1016/j.nlm.2010.11.003. Epub 2010 Nov 23. Neurobiol Learn Mem. 2011. PMID: 21081173 Free PMC article. Review.
- Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases.Ji S, Xiong M, Chen H, Liu Y, Zhou L, Hong Y, Wang M, Wang C, Fu X, Sun X. Ji S, et al. Signal Transduct Target Ther. 2023 Mar 14;8(1):116. doi: 10.1038/s41392-023-01343-5. Signal Transduct Target Ther. 2023. PMID: 36918530 Free PMC article. Review.
- Markers of aging: Unsupervised integrated analyses of the human plasma proteome.Coenen L, Lehallier B, de Vries HE, Middeldorp J. Coenen L, et al. Front Aging. 2023 Feb 22;4:1112109. doi: 10.3389/fragi.2023.1112109. eCollection 2023. Front Aging. 2023. PMID: 36911498 Free PMC article.
- Limited Proteolysis-Mass Spectrometry Reveals Aging-Associated Changes in Cerebrospinal Fluid Protein Abundances and Structures.Shuken SR, Rutledge J, Iram T, Losada PM, Wilson EN, Andreasson KI, Leib RD, Wyss-Coray T. Shuken SR, et al. Nat Aging. 2022 May;2(5):379-388. doi: 10.1038/s43587-022-00196-x. Epub 2022 Apr 11. Nat Aging. 2022. PMID: 36741774 Free PMC article.
- Blood-to-brain communication in aging and rejuvenation.Bieri G, Schroer AB, Villeda SA. Bieri G, et al. Nat Neurosci. 2023 Mar;26(3):379-393. doi: 10.1038/s41593-022-01238-8. Epub 2023 Jan 16. Nat Neurosci. 2023. PMID: 36646876 Review.
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Costanzo L, Soto B, Meier R, Geraghty P. Costanzo L, et al. Pulm Med. 2022 Dec 31;2022:3632764. doi: 10.1155/2022/3632764. eCollection 2022. Pulm Med. 2022. PMID: 36624735 Free PMC article. Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
- Aging / drug effects
- Aging / metabolism*
- Animals
- Blood Proteins / administration & dosage
- Blood Proteins / metabolism
- Blood Proteins / pharmacology*
- Cognition / drug effects
- Cognition / physiology
- Female
- Fetal Blood / chemistry*
- Hippocampus / cytology
- Hippocampus / drug effects*
- Hippocampus / physiology*
- Humans
- Long-Term Potentiation / drug effects
- Male
- Maze Learning / drug effects
- Maze Learning / physiology
- Mice
- Neuronal Plasticity / drug effects*
- Neuronal Plasticity / physiology
- Neurons / drug effects
- Neurons / physiology
- Protein Array Analysis
- Spatial Memory / drug effects
- Spatial Memory / physiology
- Tissue Inhibitor of Metalloproteinase-2 / administration & dosage
- Tissue Inhibitor of Metalloproteinase-2 / antagonists & inhibitors
- Tissue Inhibitor of Metalloproteinase-2 / metabolism
- Tissue Inhibitor of Metalloproteinase-2 / pharmacology
- Blood Proteins
- TIMP2 protein, human
- Tissue Inhibitor of Metalloproteinase-2
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Extended Data Figure 3. Human cord plasma…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f7.jpg)
Extended Data Figure 4. Most c-Fos-expressing cells…
Extended Data Figure 4. Most c-Fos-expressing cells activated by cord plasma in dentate gyrus are…
Extended Data Figure 5. Cord, but not…
Extended Data Figure 5. Cord, but not young or elderly plasma, affects LTP in aged…
Extended Data Figure 6. Systemic treatment with…
Extended Data Figure 6. Systemic treatment with CSF2 improves learning and memory in aged mice
Extended Data Figure 7. TIMP2 decreases early…
Extended Data Figure 7. TIMP2 decreases early in plasma and hippocampus and enters the CNS…
Extended Data Figure 8. Effect of systemic…
Extended Data Figure 8. Effect of systemic TIMP2 treatment or whole-body TIMP2 deletion on dentate…
Extended Data Figure 9. Systemic TIMP2 neutralization…
Extended Data Figure 9. Systemic TIMP2 neutralization alters spatial memory but not activity or general…
Extended Data Figure 10. TIMP2 is critical…
Extended Data Figure 10. TIMP2 is critical for several cognitive benefits of cord plasma independent…
Figure 1. Human cord plasma enhances plasticity…
Figure 1. Human cord plasma enhances plasticity in the aged brain
Figure 2. Cord plasma improves neuronal function…
Figure 2. Cord plasma improves neuronal function within aged hippocampus
Figure 3. Protein microarray analysis identifies putative…
Figure 3. Protein microarray analysis identifies putative pro-plasticity factors
Figure 4. Systemic TIMP2 treatment improves neuronal…
Figure 4. Systemic TIMP2 treatment improves neuronal function within aged hippocampus and is critical for…
- Ageing: Are the secrets of healthy ageing within 'young blood'?Morris A. Morris A. Nat Rev Endocrinol. 2017 Jul;13(7):376. doi: 10.1038/nrendo.2017.60. Epub 2017 May 5. Nat Rev Endocrinol. 2017. PMID: 28474688 No abstract available.
- Brain ageing: A youthful reminder.Yates D. Yates D. Nat Rev Neurosci. 2017 Jun;18(6):322-323. doi: 10.1038/nrn.2017.59. Epub 2017 May 11. Nat Rev Neurosci. 2017. PMID: 28490778 No abstract available.
- Ageing: A youthful reminder.Yates D. Yates D. Nat Rev Drug Discov. 2017 May 31;16(6):384-385. doi: 10.1038/nrd.2017.112. Nat Rev Drug Discov. 2017. PMID: 28559551 No abstract available.
- Ageing: Rejuvenation study stirs old memories.Krischel M, Hansson N. Krischel M, et al. Nature. 2017 May 31;546(7656):33. doi: 10.1038/546033e. Nature. 2017. PMID: 28569802 No abstract available.
- Long-term enzyme replacement therapy improves neurocognitive functioning and hippocampal synaptic plasticity in immune-tolerant alpha-mannosidosis mice.Stroobants S, Damme M, Van der Jeugd A, Vermaercke B, Andersson C, Fogh J, Saftig P, Blanz J, D'Hooge R. Stroobants S, et al. Neurobiol Dis. 2017 Oct;106:255-268. doi: 10.1016/j.nbd.2017.07.013. Epub 2017 Jul 15. Neurobiol Dis. 2017. PMID: 28720484
- Structure-function-behavior relationship in estrogen-induced synaptic plasticity.Vierk R, Bayer J, Freitag S, Muhia M, Kutsche K, Wolbers T, Kneussel M, Sommer T, Rune GM. Vierk R, et al. Horm Behav. 2015 Aug;74:139-48. doi: 10.1016/j.yhbeh.2015.05.008. Epub 2015 May 24. Horm Behav. 2015. PMID: 26012713
- Tripchlorolide improves age-associated cognitive deficits by reversing hippocampal synaptic plasticity impairment and NMDA receptor dysfunction in SAMP8 mice.Lin N, Pan XD, Chen AQ, Zhu YG, Wu M, Zhang J, Chen XC. Lin N, et al. Behav Brain Res. 2014 Jan 1;258:8-18. doi: 10.1016/j.bbr.2013.10.010. Epub 2013 Oct 17. Behav Brain Res. 2014. PMID: 24140565
- Ageing, hippocampal synaptic activity and magnesium.Billard JM. Billard JM. Magnes Res. 2006 Sep;19(3):199-215. Magnes Res. 2006. PMID: 17172010 Review.
- Ovarian hormones, aging and stress on hippocampal synaptic plasticity.Foy MR. Foy MR. Neurobiol Learn Mem. 2011 Feb;95(2):134-44. doi: 10.1016/j.nlm.2010.11.003. Epub 2010 Nov 23. Neurobiol Learn Mem. 2011. PMID: 21081173 Free PMC article. Review.
- Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases.Ji S, Xiong M, Chen H, Liu Y, Zhou L, Hong Y, Wang M, Wang C, Fu X, Sun X. Ji S, et al. Signal Transduct Target Ther. 2023 Mar 14;8(1):116. doi: 10.1038/s41392-023-01343-5. Signal Transduct Target Ther. 2023. PMID: 36918530 Free PMC article. Review.
- Markers of aging: Unsupervised integrated analyses of the human plasma proteome.Coenen L, Lehallier B, de Vries HE, Middeldorp J. Coenen L, et al. Front Aging. 2023 Feb 22;4:1112109. doi: 10.3389/fragi.2023.1112109. eCollection 2023. Front Aging. 2023. PMID: 36911498 Free PMC article.
- Limited Proteolysis-Mass Spectrometry Reveals Aging-Associated Changes in Cerebrospinal Fluid Protein Abundances and Structures.Shuken SR, Rutledge J, Iram T, Losada PM, Wilson EN, Andreasson KI, Leib RD, Wyss-Coray T. Shuken SR, et al. Nat Aging. 2022 May;2(5):379-388. doi: 10.1038/s43587-022-00196-x. Epub 2022 Apr 11. Nat Aging. 2022. PMID: 36741774 Free PMC article.
- Blood-to-brain communication in aging and rejuvenation.Bieri G, Schroer AB, Villeda SA. Bieri G, et al. Nat Neurosci. 2023 Mar;26(3):379-393. doi: 10.1038/s41593-022-01238-8. Epub 2023 Jan 16. Nat Neurosci. 2023. PMID: 36646876 Review.
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Costanzo L, Soto B, Meier R, Geraghty P. Costanzo L, et al. Pulm Med. 2022 Dec 31;2022:3632764. doi: 10.1155/2022/3632764. eCollection 2022. Pulm Med. 2022. PMID: 36624735 Free PMC article. Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
- Aging / drug effects
- Aging / metabolism*
- Animals
- Blood Proteins / administration & dosage
- Blood Proteins / metabolism
- Blood Proteins / pharmacology*
- Cognition / drug effects
- Cognition / physiology
- Female
- Fetal Blood / chemistry*
- Hippocampus / cytology
- Hippocampus / drug effects*
- Hippocampus / physiology*
- Humans
- Long-Term Potentiation / drug effects
- Male
- Maze Learning / drug effects
- Maze Learning / physiology
- Mice
- Neuronal Plasticity / drug effects*
- Neuronal Plasticity / physiology
- Neurons / drug effects
- Neurons / physiology
- Protein Array Analysis
- Spatial Memory / drug effects
- Spatial Memory / physiology
- Tissue Inhibitor of Metalloproteinase-2 / administration & dosage
- Tissue Inhibitor of Metalloproteinase-2 / antagonists & inhibitors
- Tissue Inhibitor of Metalloproteinase-2 / metabolism
- Tissue Inhibitor of Metalloproteinase-2 / pharmacology
- Blood Proteins
- TIMP2 protein, human
- Tissue Inhibitor of Metalloproteinase-2
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Extended Data Figure 4. Most c-Fos-expressing cells…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f8.jpg)
Extended Data Figure 5. Cord, but not…
Extended Data Figure 5. Cord, but not young or elderly plasma, affects LTP in aged…
Extended Data Figure 6. Systemic treatment with…
Extended Data Figure 6. Systemic treatment with CSF2 improves learning and memory in aged mice
Extended Data Figure 7. TIMP2 decreases early…
Extended Data Figure 7. TIMP2 decreases early in plasma and hippocampus and enters the CNS…
Extended Data Figure 8. Effect of systemic…
Extended Data Figure 8. Effect of systemic TIMP2 treatment or whole-body TIMP2 deletion on dentate…
Extended Data Figure 9. Systemic TIMP2 neutralization…
Extended Data Figure 9. Systemic TIMP2 neutralization alters spatial memory but not activity or general…
Extended Data Figure 10. TIMP2 is critical…
Extended Data Figure 10. TIMP2 is critical for several cognitive benefits of cord plasma independent…
Figure 1. Human cord plasma enhances plasticity…
Figure 1. Human cord plasma enhances plasticity in the aged brain
Figure 2. Cord plasma improves neuronal function…
Figure 2. Cord plasma improves neuronal function within aged hippocampus
Figure 3. Protein microarray analysis identifies putative…
Figure 3. Protein microarray analysis identifies putative pro-plasticity factors
Figure 4. Systemic TIMP2 treatment improves neuronal…
Figure 4. Systemic TIMP2 treatment improves neuronal function within aged hippocampus and is critical for…
- Ageing: Are the secrets of healthy ageing within 'young blood'?Morris A. Morris A. Nat Rev Endocrinol. 2017 Jul;13(7):376. doi: 10.1038/nrendo.2017.60. Epub 2017 May 5. Nat Rev Endocrinol. 2017. PMID: 28474688 No abstract available.
- Brain ageing: A youthful reminder.Yates D. Yates D. Nat Rev Neurosci. 2017 Jun;18(6):322-323. doi: 10.1038/nrn.2017.59. Epub 2017 May 11. Nat Rev Neurosci. 2017. PMID: 28490778 No abstract available.
- Ageing: A youthful reminder.Yates D. Yates D. Nat Rev Drug Discov. 2017 May 31;16(6):384-385. doi: 10.1038/nrd.2017.112. Nat Rev Drug Discov. 2017. PMID: 28559551 No abstract available.
- Ageing: Rejuvenation study stirs old memories.Krischel M, Hansson N. Krischel M, et al. Nature. 2017 May 31;546(7656):33. doi: 10.1038/546033e. Nature. 2017. PMID: 28569802 No abstract available.
- Long-term enzyme replacement therapy improves neurocognitive functioning and hippocampal synaptic plasticity in immune-tolerant alpha-mannosidosis mice.Stroobants S, Damme M, Van der Jeugd A, Vermaercke B, Andersson C, Fogh J, Saftig P, Blanz J, D'Hooge R. Stroobants S, et al. Neurobiol Dis. 2017 Oct;106:255-268. doi: 10.1016/j.nbd.2017.07.013. Epub 2017 Jul 15. Neurobiol Dis. 2017. PMID: 28720484
- Structure-function-behavior relationship in estrogen-induced synaptic plasticity.Vierk R, Bayer J, Freitag S, Muhia M, Kutsche K, Wolbers T, Kneussel M, Sommer T, Rune GM. Vierk R, et al. Horm Behav. 2015 Aug;74:139-48. doi: 10.1016/j.yhbeh.2015.05.008. Epub 2015 May 24. Horm Behav. 2015. PMID: 26012713
- Tripchlorolide improves age-associated cognitive deficits by reversing hippocampal synaptic plasticity impairment and NMDA receptor dysfunction in SAMP8 mice.Lin N, Pan XD, Chen AQ, Zhu YG, Wu M, Zhang J, Chen XC. Lin N, et al. Behav Brain Res. 2014 Jan 1;258:8-18. doi: 10.1016/j.bbr.2013.10.010. Epub 2013 Oct 17. Behav Brain Res. 2014. PMID: 24140565
- Ageing, hippocampal synaptic activity and magnesium.Billard JM. Billard JM. Magnes Res. 2006 Sep;19(3):199-215. Magnes Res. 2006. PMID: 17172010 Review.
- Ovarian hormones, aging and stress on hippocampal synaptic plasticity.Foy MR. Foy MR. Neurobiol Learn Mem. 2011 Feb;95(2):134-44. doi: 10.1016/j.nlm.2010.11.003. Epub 2010 Nov 23. Neurobiol Learn Mem. 2011. PMID: 21081173 Free PMC article. Review.
- Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases.Ji S, Xiong M, Chen H, Liu Y, Zhou L, Hong Y, Wang M, Wang C, Fu X, Sun X. Ji S, et al. Signal Transduct Target Ther. 2023 Mar 14;8(1):116. doi: 10.1038/s41392-023-01343-5. Signal Transduct Target Ther. 2023. PMID: 36918530 Free PMC article. Review.
- Markers of aging: Unsupervised integrated analyses of the human plasma proteome.Coenen L, Lehallier B, de Vries HE, Middeldorp J. Coenen L, et al. Front Aging. 2023 Feb 22;4:1112109. doi: 10.3389/fragi.2023.1112109. eCollection 2023. Front Aging. 2023. PMID: 36911498 Free PMC article.
- Limited Proteolysis-Mass Spectrometry Reveals Aging-Associated Changes in Cerebrospinal Fluid Protein Abundances and Structures.Shuken SR, Rutledge J, Iram T, Losada PM, Wilson EN, Andreasson KI, Leib RD, Wyss-Coray T. Shuken SR, et al. Nat Aging. 2022 May;2(5):379-388. doi: 10.1038/s43587-022-00196-x. Epub 2022 Apr 11. Nat Aging. 2022. PMID: 36741774 Free PMC article.
- Blood-to-brain communication in aging and rejuvenation.Bieri G, Schroer AB, Villeda SA. Bieri G, et al. Nat Neurosci. 2023 Mar;26(3):379-393. doi: 10.1038/s41593-022-01238-8. Epub 2023 Jan 16. Nat Neurosci. 2023. PMID: 36646876 Review.
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Costanzo L, Soto B, Meier R, Geraghty P. Costanzo L, et al. Pulm Med. 2022 Dec 31;2022:3632764. doi: 10.1155/2022/3632764. eCollection 2022. Pulm Med. 2022. PMID: 36624735 Free PMC article. Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
- Aging / drug effects
- Aging / metabolism*
- Animals
- Blood Proteins / administration & dosage
- Blood Proteins / metabolism
- Blood Proteins / pharmacology*
- Cognition / drug effects
- Cognition / physiology
- Female
- Fetal Blood / chemistry*
- Hippocampus / cytology
- Hippocampus / drug effects*
- Hippocampus / physiology*
- Humans
- Long-Term Potentiation / drug effects
- Male
- Maze Learning / drug effects
- Maze Learning / physiology
- Mice
- Neuronal Plasticity / drug effects*
- Neuronal Plasticity / physiology
- Neurons / drug effects
- Neurons / physiology
- Protein Array Analysis
- Spatial Memory / drug effects
- Spatial Memory / physiology
- Tissue Inhibitor of Metalloproteinase-2 / administration & dosage
- Tissue Inhibitor of Metalloproteinase-2 / antagonists & inhibitors
- Tissue Inhibitor of Metalloproteinase-2 / metabolism
- Tissue Inhibitor of Metalloproteinase-2 / pharmacology
- Blood Proteins
- TIMP2 protein, human
- Tissue Inhibitor of Metalloproteinase-2
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
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![Extended Data Figure 5. Cord, but not…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f9.jpg)
![Extended Data Figure 6. Systemic treatment with…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f10.jpg)
![Extended Data Figure 7. TIMP2 decreases early…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f11.jpg)
Extended Data Figure 8. Effect of systemic…
Extended Data Figure 8. Effect of systemic TIMP2 treatment or whole-body TIMP2 deletion on dentate…
Extended Data Figure 9. Systemic TIMP2 neutralization…
Extended Data Figure 9. Systemic TIMP2 neutralization alters spatial memory but not activity or general…
Extended Data Figure 10. TIMP2 is critical…
Extended Data Figure 10. TIMP2 is critical for several cognitive benefits of cord plasma independent…
Figure 1. Human cord plasma enhances plasticity…
Figure 1. Human cord plasma enhances plasticity in the aged brain
Figure 2. Cord plasma improves neuronal function…
Figure 2. Cord plasma improves neuronal function within aged hippocampus
Figure 3. Protein microarray analysis identifies putative…
Figure 3. Protein microarray analysis identifies putative pro-plasticity factors
Figure 4. Systemic TIMP2 treatment improves neuronal…
Figure 4. Systemic TIMP2 treatment improves neuronal function within aged hippocampus and is critical for…
- Ageing: Are the secrets of healthy ageing within 'young blood'?Morris A. Morris A. Nat Rev Endocrinol. 2017 Jul;13(7):376. doi: 10.1038/nrendo.2017.60. Epub 2017 May 5. Nat Rev Endocrinol. 2017. PMID: 28474688 No abstract available.
- Brain ageing: A youthful reminder.Yates D. Yates D. Nat Rev Neurosci. 2017 Jun;18(6):322-323. doi: 10.1038/nrn.2017.59. Epub 2017 May 11. Nat Rev Neurosci. 2017. PMID: 28490778 No abstract available.
- Ageing: A youthful reminder.Yates D. Yates D. Nat Rev Drug Discov. 2017 May 31;16(6):384-385. doi: 10.1038/nrd.2017.112. Nat Rev Drug Discov. 2017. PMID: 28559551 No abstract available.
- Ageing: Rejuvenation study stirs old memories.Krischel M, Hansson N. Krischel M, et al. Nature. 2017 May 31;546(7656):33. doi: 10.1038/546033e. Nature. 2017. PMID: 28569802 No abstract available.
- Long-term enzyme replacement therapy improves neurocognitive functioning and hippocampal synaptic plasticity in immune-tolerant alpha-mannosidosis mice.Stroobants S, Damme M, Van der Jeugd A, Vermaercke B, Andersson C, Fogh J, Saftig P, Blanz J, D'Hooge R. Stroobants S, et al. Neurobiol Dis. 2017 Oct;106:255-268. doi: 10.1016/j.nbd.2017.07.013. Epub 2017 Jul 15. Neurobiol Dis. 2017. PMID: 28720484
- Structure-function-behavior relationship in estrogen-induced synaptic plasticity.Vierk R, Bayer J, Freitag S, Muhia M, Kutsche K, Wolbers T, Kneussel M, Sommer T, Rune GM. Vierk R, et al. Horm Behav. 2015 Aug;74:139-48. doi: 10.1016/j.yhbeh.2015.05.008. Epub 2015 May 24. Horm Behav. 2015. PMID: 26012713
- Tripchlorolide improves age-associated cognitive deficits by reversing hippocampal synaptic plasticity impairment and NMDA receptor dysfunction in SAMP8 mice.Lin N, Pan XD, Chen AQ, Zhu YG, Wu M, Zhang J, Chen XC. Lin N, et al. Behav Brain Res. 2014 Jan 1;258:8-18. doi: 10.1016/j.bbr.2013.10.010. Epub 2013 Oct 17. Behav Brain Res. 2014. PMID: 24140565
- Ageing, hippocampal synaptic activity and magnesium.Billard JM. Billard JM. Magnes Res. 2006 Sep;19(3):199-215. Magnes Res. 2006. PMID: 17172010 Review.
- Ovarian hormones, aging and stress on hippocampal synaptic plasticity.Foy MR. Foy MR. Neurobiol Learn Mem. 2011 Feb;95(2):134-44. doi: 10.1016/j.nlm.2010.11.003. Epub 2010 Nov 23. Neurobiol Learn Mem. 2011. PMID: 21081173 Free PMC article. Review.
- Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases.Ji S, Xiong M, Chen H, Liu Y, Zhou L, Hong Y, Wang M, Wang C, Fu X, Sun X. Ji S, et al. Signal Transduct Target Ther. 2023 Mar 14;8(1):116. doi: 10.1038/s41392-023-01343-5. Signal Transduct Target Ther. 2023. PMID: 36918530 Free PMC article. Review.
- Markers of aging: Unsupervised integrated analyses of the human plasma proteome.Coenen L, Lehallier B, de Vries HE, Middeldorp J. Coenen L, et al. Front Aging. 2023 Feb 22;4:1112109. doi: 10.3389/fragi.2023.1112109. eCollection 2023. Front Aging. 2023. PMID: 36911498 Free PMC article.
- Limited Proteolysis-Mass Spectrometry Reveals Aging-Associated Changes in Cerebrospinal Fluid Protein Abundances and Structures.Shuken SR, Rutledge J, Iram T, Losada PM, Wilson EN, Andreasson KI, Leib RD, Wyss-Coray T. Shuken SR, et al. Nat Aging. 2022 May;2(5):379-388. doi: 10.1038/s43587-022-00196-x. Epub 2022 Apr 11. Nat Aging. 2022. PMID: 36741774 Free PMC article.
- Blood-to-brain communication in aging and rejuvenation.Bieri G, Schroer AB, Villeda SA. Bieri G, et al. Nat Neurosci. 2023 Mar;26(3):379-393. doi: 10.1038/s41593-022-01238-8. Epub 2023 Jan 16. Nat Neurosci. 2023. PMID: 36646876 Review.
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Costanzo L, Soto B, Meier R, Geraghty P. Costanzo L, et al. Pulm Med. 2022 Dec 31;2022:3632764. doi: 10.1155/2022/3632764. eCollection 2022. Pulm Med. 2022. PMID: 36624735 Free PMC article. Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
- Aging / drug effects
- Aging / metabolism*
- Animals
- Blood Proteins / administration & dosage
- Blood Proteins / metabolism
- Blood Proteins / pharmacology*
- Cognition / drug effects
- Cognition / physiology
- Female
- Fetal Blood / chemistry*
- Hippocampus / cytology
- Hippocampus / drug effects*
- Hippocampus / physiology*
- Humans
- Long-Term Potentiation / drug effects
- Male
- Maze Learning / drug effects
- Maze Learning / physiology
- Mice
- Neuronal Plasticity / drug effects*
- Neuronal Plasticity / physiology
- Neurons / drug effects
- Neurons / physiology
- Protein Array Analysis
- Spatial Memory / drug effects
- Spatial Memory / physiology
- Tissue Inhibitor of Metalloproteinase-2 / administration & dosage
- Tissue Inhibitor of Metalloproteinase-2 / antagonists & inhibitors
- Tissue Inhibitor of Metalloproteinase-2 / metabolism
- Tissue Inhibitor of Metalloproteinase-2 / pharmacology
- Blood Proteins
- TIMP2 protein, human
- Tissue Inhibitor of Metalloproteinase-2
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Extended Data Figure 8. Effect of systemic…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f12.jpg)
Extended Data Figure 9. Systemic TIMP2 neutralization…
Extended Data Figure 9. Systemic TIMP2 neutralization alters spatial memory but not activity or general…
Extended Data Figure 10. TIMP2 is critical…
Extended Data Figure 10. TIMP2 is critical for several cognitive benefits of cord plasma independent…
Figure 1. Human cord plasma enhances plasticity…
Figure 1. Human cord plasma enhances plasticity in the aged brain
Figure 2. Cord plasma improves neuronal function…
Figure 2. Cord plasma improves neuronal function within aged hippocampus
Figure 3. Protein microarray analysis identifies putative…
Figure 3. Protein microarray analysis identifies putative pro-plasticity factors
Figure 4. Systemic TIMP2 treatment improves neuronal…
Figure 4. Systemic TIMP2 treatment improves neuronal function within aged hippocampus and is critical for…
- Ageing: Are the secrets of healthy ageing within 'young blood'?Morris A. Morris A. Nat Rev Endocrinol. 2017 Jul;13(7):376. doi: 10.1038/nrendo.2017.60. Epub 2017 May 5. Nat Rev Endocrinol. 2017. PMID: 28474688 No abstract available.
- Brain ageing: A youthful reminder.Yates D. Yates D. Nat Rev Neurosci. 2017 Jun;18(6):322-323. doi: 10.1038/nrn.2017.59. Epub 2017 May 11. Nat Rev Neurosci. 2017. PMID: 28490778 No abstract available.
- Ageing: A youthful reminder.Yates D. Yates D. Nat Rev Drug Discov. 2017 May 31;16(6):384-385. doi: 10.1038/nrd.2017.112. Nat Rev Drug Discov. 2017. PMID: 28559551 No abstract available.
- Ageing: Rejuvenation study stirs old memories.Krischel M, Hansson N. Krischel M, et al. Nature. 2017 May 31;546(7656):33. doi: 10.1038/546033e. Nature. 2017. PMID: 28569802 No abstract available.
- Long-term enzyme replacement therapy improves neurocognitive functioning and hippocampal synaptic plasticity in immune-tolerant alpha-mannosidosis mice.Stroobants S, Damme M, Van der Jeugd A, Vermaercke B, Andersson C, Fogh J, Saftig P, Blanz J, D'Hooge R. Stroobants S, et al. Neurobiol Dis. 2017 Oct;106:255-268. doi: 10.1016/j.nbd.2017.07.013. Epub 2017 Jul 15. Neurobiol Dis. 2017. PMID: 28720484
- Structure-function-behavior relationship in estrogen-induced synaptic plasticity.Vierk R, Bayer J, Freitag S, Muhia M, Kutsche K, Wolbers T, Kneussel M, Sommer T, Rune GM. Vierk R, et al. Horm Behav. 2015 Aug;74:139-48. doi: 10.1016/j.yhbeh.2015.05.008. Epub 2015 May 24. Horm Behav. 2015. PMID: 26012713
- Tripchlorolide improves age-associated cognitive deficits by reversing hippocampal synaptic plasticity impairment and NMDA receptor dysfunction in SAMP8 mice.Lin N, Pan XD, Chen AQ, Zhu YG, Wu M, Zhang J, Chen XC. Lin N, et al. Behav Brain Res. 2014 Jan 1;258:8-18. doi: 10.1016/j.bbr.2013.10.010. Epub 2013 Oct 17. Behav Brain Res. 2014. PMID: 24140565
- Ageing, hippocampal synaptic activity and magnesium.Billard JM. Billard JM. Magnes Res. 2006 Sep;19(3):199-215. Magnes Res. 2006. PMID: 17172010 Review.
- Ovarian hormones, aging and stress on hippocampal synaptic plasticity.Foy MR. Foy MR. Neurobiol Learn Mem. 2011 Feb;95(2):134-44. doi: 10.1016/j.nlm.2010.11.003. Epub 2010 Nov 23. Neurobiol Learn Mem. 2011. PMID: 21081173 Free PMC article. Review.
- Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases.Ji S, Xiong M, Chen H, Liu Y, Zhou L, Hong Y, Wang M, Wang C, Fu X, Sun X. Ji S, et al. Signal Transduct Target Ther. 2023 Mar 14;8(1):116. doi: 10.1038/s41392-023-01343-5. Signal Transduct Target Ther. 2023. PMID: 36918530 Free PMC article. Review.
- Markers of aging: Unsupervised integrated analyses of the human plasma proteome.Coenen L, Lehallier B, de Vries HE, Middeldorp J. Coenen L, et al. Front Aging. 2023 Feb 22;4:1112109. doi: 10.3389/fragi.2023.1112109. eCollection 2023. Front Aging. 2023. PMID: 36911498 Free PMC article.
- Limited Proteolysis-Mass Spectrometry Reveals Aging-Associated Changes in Cerebrospinal Fluid Protein Abundances and Structures.Shuken SR, Rutledge J, Iram T, Losada PM, Wilson EN, Andreasson KI, Leib RD, Wyss-Coray T. Shuken SR, et al. Nat Aging. 2022 May;2(5):379-388. doi: 10.1038/s43587-022-00196-x. Epub 2022 Apr 11. Nat Aging. 2022. PMID: 36741774 Free PMC article.
- Blood-to-brain communication in aging and rejuvenation.Bieri G, Schroer AB, Villeda SA. Bieri G, et al. Nat Neurosci. 2023 Mar;26(3):379-393. doi: 10.1038/s41593-022-01238-8. Epub 2023 Jan 16. Nat Neurosci. 2023. PMID: 36646876 Review.
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Costanzo L, Soto B, Meier R, Geraghty P. Costanzo L, et al. Pulm Med. 2022 Dec 31;2022:3632764. doi: 10.1155/2022/3632764. eCollection 2022. Pulm Med. 2022. PMID: 36624735 Free PMC article. Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
- Aging / drug effects
- Aging / metabolism*
- Animals
- Blood Proteins / administration & dosage
- Blood Proteins / metabolism
- Blood Proteins / pharmacology*
- Cognition / drug effects
- Cognition / physiology
- Female
- Fetal Blood / chemistry*
- Hippocampus / cytology
- Hippocampus / drug effects*
- Hippocampus / physiology*
- Humans
- Long-Term Potentiation / drug effects
- Male
- Maze Learning / drug effects
- Maze Learning / physiology
- Mice
- Neuronal Plasticity / drug effects*
- Neuronal Plasticity / physiology
- Neurons / drug effects
- Neurons / physiology
- Protein Array Analysis
- Spatial Memory / drug effects
- Spatial Memory / physiology
- Tissue Inhibitor of Metalloproteinase-2 / administration & dosage
- Tissue Inhibitor of Metalloproteinase-2 / antagonists & inhibitors
- Tissue Inhibitor of Metalloproteinase-2 / metabolism
- Tissue Inhibitor of Metalloproteinase-2 / pharmacology
- Blood Proteins
- TIMP2 protein, human
- Tissue Inhibitor of Metalloproteinase-2
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Extended Data Figure 9. Systemic TIMP2 neutralization…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f13.jpg)
Extended Data Figure 10. TIMP2 is critical…
Extended Data Figure 10. TIMP2 is critical for several cognitive benefits of cord plasma independent…
Figure 1. Human cord plasma enhances plasticity…
Figure 1. Human cord plasma enhances plasticity in the aged brain
Figure 2. Cord plasma improves neuronal function…
Figure 2. Cord plasma improves neuronal function within aged hippocampus
Figure 3. Protein microarray analysis identifies putative…
Figure 3. Protein microarray analysis identifies putative pro-plasticity factors
Figure 4. Systemic TIMP2 treatment improves neuronal…
Figure 4. Systemic TIMP2 treatment improves neuronal function within aged hippocampus and is critical for…
- Ageing: Are the secrets of healthy ageing within 'young blood'?Morris A. Morris A. Nat Rev Endocrinol. 2017 Jul;13(7):376. doi: 10.1038/nrendo.2017.60. Epub 2017 May 5. Nat Rev Endocrinol. 2017. PMID: 28474688 No abstract available.
- Brain ageing: A youthful reminder.Yates D. Yates D. Nat Rev Neurosci. 2017 Jun;18(6):322-323. doi: 10.1038/nrn.2017.59. Epub 2017 May 11. Nat Rev Neurosci. 2017. PMID: 28490778 No abstract available.
- Ageing: A youthful reminder.Yates D. Yates D. Nat Rev Drug Discov. 2017 May 31;16(6):384-385. doi: 10.1038/nrd.2017.112. Nat Rev Drug Discov. 2017. PMID: 28559551 No abstract available.
- Ageing: Rejuvenation study stirs old memories.Krischel M, Hansson N. Krischel M, et al. Nature. 2017 May 31;546(7656):33. doi: 10.1038/546033e. Nature. 2017. PMID: 28569802 No abstract available.
- Long-term enzyme replacement therapy improves neurocognitive functioning and hippocampal synaptic plasticity in immune-tolerant alpha-mannosidosis mice.Stroobants S, Damme M, Van der Jeugd A, Vermaercke B, Andersson C, Fogh J, Saftig P, Blanz J, D'Hooge R. Stroobants S, et al. Neurobiol Dis. 2017 Oct;106:255-268. doi: 10.1016/j.nbd.2017.07.013. Epub 2017 Jul 15. Neurobiol Dis. 2017. PMID: 28720484
- Structure-function-behavior relationship in estrogen-induced synaptic plasticity.Vierk R, Bayer J, Freitag S, Muhia M, Kutsche K, Wolbers T, Kneussel M, Sommer T, Rune GM. Vierk R, et al. Horm Behav. 2015 Aug;74:139-48. doi: 10.1016/j.yhbeh.2015.05.008. Epub 2015 May 24. Horm Behav. 2015. PMID: 26012713
- Tripchlorolide improves age-associated cognitive deficits by reversing hippocampal synaptic plasticity impairment and NMDA receptor dysfunction in SAMP8 mice.Lin N, Pan XD, Chen AQ, Zhu YG, Wu M, Zhang J, Chen XC. Lin N, et al. Behav Brain Res. 2014 Jan 1;258:8-18. doi: 10.1016/j.bbr.2013.10.010. Epub 2013 Oct 17. Behav Brain Res. 2014. PMID: 24140565
- Ageing, hippocampal synaptic activity and magnesium.Billard JM. Billard JM. Magnes Res. 2006 Sep;19(3):199-215. Magnes Res. 2006. PMID: 17172010 Review.
- Ovarian hormones, aging and stress on hippocampal synaptic plasticity.Foy MR. Foy MR. Neurobiol Learn Mem. 2011 Feb;95(2):134-44. doi: 10.1016/j.nlm.2010.11.003. Epub 2010 Nov 23. Neurobiol Learn Mem. 2011. PMID: 21081173 Free PMC article. Review.
- Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases.Ji S, Xiong M, Chen H, Liu Y, Zhou L, Hong Y, Wang M, Wang C, Fu X, Sun X. Ji S, et al. Signal Transduct Target Ther. 2023 Mar 14;8(1):116. doi: 10.1038/s41392-023-01343-5. Signal Transduct Target Ther. 2023. PMID: 36918530 Free PMC article. Review.
- Markers of aging: Unsupervised integrated analyses of the human plasma proteome.Coenen L, Lehallier B, de Vries HE, Middeldorp J. Coenen L, et al. Front Aging. 2023 Feb 22;4:1112109. doi: 10.3389/fragi.2023.1112109. eCollection 2023. Front Aging. 2023. PMID: 36911498 Free PMC article.
- Limited Proteolysis-Mass Spectrometry Reveals Aging-Associated Changes in Cerebrospinal Fluid Protein Abundances and Structures.Shuken SR, Rutledge J, Iram T, Losada PM, Wilson EN, Andreasson KI, Leib RD, Wyss-Coray T. Shuken SR, et al. Nat Aging. 2022 May;2(5):379-388. doi: 10.1038/s43587-022-00196-x. Epub 2022 Apr 11. Nat Aging. 2022. PMID: 36741774 Free PMC article.
- Blood-to-brain communication in aging and rejuvenation.Bieri G, Schroer AB, Villeda SA. Bieri G, et al. Nat Neurosci. 2023 Mar;26(3):379-393. doi: 10.1038/s41593-022-01238-8. Epub 2023 Jan 16. Nat Neurosci. 2023. PMID: 36646876 Review.
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Costanzo L, Soto B, Meier R, Geraghty P. Costanzo L, et al. Pulm Med. 2022 Dec 31;2022:3632764. doi: 10.1155/2022/3632764. eCollection 2022. Pulm Med. 2022. PMID: 36624735 Free PMC article. Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
- Aging / drug effects
- Aging / metabolism*
- Animals
- Blood Proteins / administration & dosage
- Blood Proteins / metabolism
- Blood Proteins / pharmacology*
- Cognition / drug effects
- Cognition / physiology
- Female
- Fetal Blood / chemistry*
- Hippocampus / cytology
- Hippocampus / drug effects*
- Hippocampus / physiology*
- Humans
- Long-Term Potentiation / drug effects
- Male
- Maze Learning / drug effects
- Maze Learning / physiology
- Mice
- Neuronal Plasticity / drug effects*
- Neuronal Plasticity / physiology
- Neurons / drug effects
- Neurons / physiology
- Protein Array Analysis
- Spatial Memory / drug effects
- Spatial Memory / physiology
- Tissue Inhibitor of Metalloproteinase-2 / administration & dosage
- Tissue Inhibitor of Metalloproteinase-2 / antagonists & inhibitors
- Tissue Inhibitor of Metalloproteinase-2 / metabolism
- Tissue Inhibitor of Metalloproteinase-2 / pharmacology
- Blood Proteins
- TIMP2 protein, human
- Tissue Inhibitor of Metalloproteinase-2
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Miscellaneous
![Extended Data Figure 10. TIMP2 is critical…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f14.jpg)
Figure 1. Human cord plasma enhances plasticity…
Figure 1. Human cord plasma enhances plasticity in the aged brain
Figure 2. Cord plasma improves neuronal function…
Figure 2. Cord plasma improves neuronal function within aged hippocampus
Figure 3. Protein microarray analysis identifies putative…
Figure 3. Protein microarray analysis identifies putative pro-plasticity factors
Figure 4. Systemic TIMP2 treatment improves neuronal…
Figure 4. Systemic TIMP2 treatment improves neuronal function within aged hippocampus and is critical for…
![Figure 1. Human cord plasma enhances plasticity…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f1.jpg)
![Figure 2. Cord plasma improves neuronal function…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f2.jpg)
![Figure 3. Protein microarray analysis identifies putative…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f3.jpg)
![Figure 4. Systemic TIMP2 treatment improves neuronal…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5586222/bin/nihms901457f4.jpg)
Source: PubMed