Blood-Borne Revitalization of the Aged Brain
Open accessAbstract
In the modern medical era, more diverse and effective treatment options have translated to increased life expectancy. With this increased life span comes increased age-associated disease and the dire need to understand underlying causes so that therapies can be designed to mitigate the burden to health and the economy. Aging exacts a seemingly inevitable multisystem deterioration of function that acts as a risk factor for a variety of age-related disorders, including those that devastate organs of limited regenerative potential, such as the brain. Rather than studying the brain and mechanisms that govern its aging in isolation from other organ systems, an emerging approach is to understand the relatively unappreciated communication that exists between the brain and systemic environment. Revisiting classical methods of experimental physiology in animal models has uncovered surprising regenerative activity in young blood with translational implications for the aging liver, muscle, brain, and other organs. Soluble factors present in young or aged blood are sufficient to improve or impair cognitive function, respectively, suggesting an aging continuum of brain-relevant systemic factors. The age-associated plasma chemokine CCL11 has been shown to impair young brain function while GDF11 has been reported to increase the generation of neurons in aged mice. However, the identities of specific factors mediating memory-enhancing effects of young blood and their mechanisms of action are enigmatic. Here we review brain rejuvenation studies in the broader context of systemic rejuvenation research. We discuss putative mechanisms for blood-borne brain rejuvenation and suggest promising avenues for future research and development of therapies.
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Selective supplementation of blood-derived antiageing factors holds promise for revitalizing the aged brain.
“The selective supplementation of blood-derived antiageing factors holds promise for revitalizing the aged brain.379”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [379]
Young blood prolongs the BA of aged recipients via epigenetic remodelling and rejuvenates various organs, including the brain.
“young blood prolongs the BA of aged recipients via epigenetic remodelling447 and rejuvenates various organs, including the brain.379,448”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [379]
The role of blood-borne factors in aging-associated physiological and behavioral alterations in the brain has garnered further credence and offers therapeutic promise.
“Although the definitive role of GDF11 in aging-induced vascular deficits was challenged by subsequent studies, the role of blood-borne factors in aging-associated physiological and behavioral alterations in the brain has garnered further credence and offers therapeutic promise (Castellano et al, 2015;Egerman et al, 2015).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Castellano et al, 2015
The definitive role of GDF11 in aging-induced vascular deficits was challenged by subsequent studies.
“Although the definitive role of GDF11 in aging-induced vascular deficits was challenged by subsequent studies, the role of blood-borne factors in aging-associated physiological and behavioral alterations in the brain has garnered further credence and offers therapeutic promise (Castellano et al, 2015;Egerman et al, 2015).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Castellano et al, 2015
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Aging Principles and Perspectives for Intervention
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- Authors
- Castellano, J. M., Kirby, E. D., & Wyss-Coray, T.
- Affiliations
- Stanford Medicine (US)
- Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California2Center for Tissue Regeneration, Repair, and Restoration, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2015-10-01
- Volume
- 72
- Issue
- 10
- Pages
- 1191
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC4867550
- OpenAlex
- W1788631067
- Cited by
- 83
- References
- 16
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 11 · 2023: 5 · 2022: 10 · 2021: 9 · 2020: 6 · 2019: 11 · 2018: 15 · 2017: 4 · 2016: 6 · 2015: 1
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG045034)
- National Institute of Neurological Disorders and Stroke (F32NS083508, R00NS089938, K99NS089938, NS083508)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- brain rejuvenation, brain aging, young blood, blood-borne factors, eotaxin, GDF11, neurogenesis, cognitive function, age-related diseases, plasma chemokines, memory enhancement
- MeSH terms
- Aging, Animals, Brain, Cognition, Humans, Memory, Neurons, Rejuvenation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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