Blood-Borne Revitalization of the Aged Brain

Castellano, Joseph M.; Kirby, Elizabeth D.; Wyss‐Coray, Tony

doi:10.1001/jamaneurol.2015.1616

Cited by 71 publications

(45 citation statements)

References 16 publications

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“…Blood is a sensitive marker of functional aging but also plays an active role in aging. Numerous studies have shown that soluble factors from young mouse blood reverse aspects of aging and disease across multiple tissues [5][6][7][8][9][10][11][12][13]35 . Here, we describe a 46-protein aging signature that is conserved in humans and mice, containing several known aging proteins such GDF15 36 and IGF1/INSR 37 but also less investigated ones (Fig 1l).…”

Section: Discussionmentioning

confidence: 99%

Undulating changes in human plasma proteome across lifespan are linked to disease

Lehallier

Gate

Schaum

et al. 2019

Preprint

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Aging is the predominant risk factor for numerous chronic diseases that limit healthspan. Mechanisms of aging are thus increasingly recognized as therapeutic targets. Blood from young mice reverses aspects of aging and disease across multiple tissues, pointing to the intriguing possibility that age-related molecular changes in blood can provide novel insight into disease biology. We measured 2,925 plasma proteins from 4,331 young adults to nonagenarians and developed a novel bioinformatics approach which uncovered profound non-linear alterations in the human plasma proteome with age. Waves of changes in the proteome in the fourth, seventh, and eighth decades of life reflected distinct biological pathways, and revealed differential associations with the genome and proteome of age-related diseases and phenotypic traits. This new approach to the study of aging led to the identification of unexpected signatures and pathways of aging and disease and offers potential pathways for aging interventions.

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Section: Discussionmentioning

confidence: 99%

Undulating changes in human plasma proteome across lifespan are linked to disease

Lehallier

Gate

Schaum

et al. 2019

Preprint

Self Cite

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“…The recent report of rejuvenation in elderly rodents from infusion of plasma from young adult but not from old adult humans may reflect differences in kinetic activity of the body's fluids as a function of age [25].…”

Section: Agricultural Studies Disease Resistance and Delayed Agingmentioning

confidence: 99%

Alternative Cellular Energy as a Unifying Concept in Complementary Alternative Medicine

Martin¹

2015

IJCAM

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Energy allows cells to function and an insufficiency of cellular energy (ICE) explains many disease processes. Food metabolism has generally been viewed as providing the energy required for cellular functions, with additional direct energy input available for plants and certain bacterial through photosynthesis. This view can now be expanded with the description of the third or alternative cellular energy (ACE) pathway. The clinical benefits of several major modalities of complementary alternative medicine (CAM) may be explained as enhancing the ACE pathway. Further progress in this area should help minimize the future need for pharmaceuticals. It will also lead to a better understanding of the body as an antenna for absorbing a proposed natural energy force termed KELEA (kinetic energy limiting electrostatic attraction).

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“…At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation 2, 3, 4 and downregulated in the aged brain 5, 6, 7, 8 . In addition to revitalizing other aged tissues 9, 10, 11, 12, 13 , exposure to factors in young blood counteracts age-related changes in these central nervous system parameters 14, 15, 16 , although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown 17 . We hypothesized that plasma of an early developmental stage, namely umbilical cord plasma, provides a reservoir of such plasticity-promoting proteins.…”

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confidence: 99%

Human umbilical cord plasma proteins revitalize hippocampal function in aged mice

Castellano

Mosher

Abbey

et al. 2017

Nature

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356

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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 potentiation1, 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 potentiation2, 3, 4 and downregulated in the aged brain5, 6, 7, 8. In addition to revitalizing other aged tissues9, 10, 11, 12, 13, exposure to factors in young blood counteracts age-related changes in these central nervous system parameters14, 15, 16, although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown17. 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.

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Blood-Borne Revitalization of the Aged Brain

Cited by 71 publications

References 16 publications

Undulating changes in human plasma proteome across lifespan are linked to disease

Undulating changes in human plasma proteome across lifespan are linked to disease

Alternative Cellular Energy as a Unifying Concept in Complementary Alternative Medicine

Human umbilical cord plasma proteins revitalize hippocampal function in aged mice

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