Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy

Loffredo, Francesco; Steinhauser, Matthew L.; Jay, Steven M.; Gannon, Joseph; Pancoast, James R.; Yalamanchi, Pratyusha; Sinha, Michael S.; Dall’Osso, Claudia; Khong, Danika; Shadrach, Jennifer L.; Miller, Christine; Singer, Britta Swebilius; Stewart, A. Keith; Psychogios, Nikolaos; Gerszten, Robert E.; Hartigan, Adam J.; Kim, Mi-Jeong; Serwold, Thomas; Wagers, Amy J.; Lee, Richard T.

doi:10.1016/j.cell.2013.04.015

Cited by 803 publications

(914 citation statements)

References 39 publications

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“…Some anti-ageing molecules, such as growth and differentiation factor 11, granulocyte-macrophage colony stimulating factor, and metalloproteinase inhibitor 2, have been identified in blood from young mice and in human umbilical cord plasma 66,67 . Whether levels of these anti-ageing molecules are reduced in patients with AD, and whether they are pathophysiologically relevant to this disease, remain unknown.…”

Section: Blood Abnormalitiesmentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

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The global burden of Alzheimer disease (AD), already the most common type of dementia, is expected to increase still further owing to population ageing. AD not only causes severe distress for patients and caregivers, but also results in a large economic burden on society. Current major challenges in AD include the lack of reliable biomarkers for its early diagnosis, as well as the lack of effective preventive strategies and treatments 1,2 . Thus, increased understanding of the molecular patho genesis of AD could lead to the development of improved diagnostic and therapeutic strategies.AD is conventionally regarded as a CNS disorder. However, increasing experimental, epidemiological and clinical evidence has suggested that manifestations of AD extend beyond the brain. These systemic alterations might not be simply secondary effects of the cerebral degeneration seen in AD, but could reflect under lying processes linked to progression of the disease. AD pathogenesis is complex, involving abnormal amyloid-β (Aβ) metabolism, tau hyperphosphorylation, oxidative stress, reactive glial and microglial changes, and other pathological events. Given that Aβ is a major hallmark of AD and a fertile area of research in this disease, this Review focuses on the systemic role of Aβ in AD. We discuss the communication between peripheral and central pools of Aβ, and describe interactions between systemic abnormalities and AD pathogenesis in the brain. We review emerging findings of associations between systemic abnormalities and Aβ metabolism, and describe how these associations might interact with or reflect on the central pathways of Aβ production and clearance. On the basis of these findings, we suggest that interactions between the brain and the periphery might have a crucial role in the development and progression of AD. Aβ biogenesis and catabolismA steady accrual of data from laboratories and clinics is providing increasing support for the concept that an imbalance between the production and clearance of Aβ is a very early (and often initiating) factor in AD 3 . Normal metabolism of Aβ and maintenance of the homeostatic balance between Aβ production and clearance is, therefore, essential to maintain brain health. In fact, physiological metabolism of Aβ occurs not only in the brain but also in the periphery, and communication between these regions is possible (FIG. 1). Central and peripheral production of AβAβ is derived from the proteolytic cleavage of amyloid precursor protein (APP), which is expressed not only in brain cells, including neurons, astrocytes and microglia, but also in peripheral organs and tissues, such as the Abstract | Alzheimer disease (AD) is the most common type of dementia, and is currently incurable; existing treatments for AD produce only a modest amelioration of symptoms. Research into this disease has conventionally focused on the CNS. However, several peripheral and systemic abnormalities are now understood to be linked to AD, and our understanding of how these alterations contribute to AD is becom...

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Section: Blood Abnormalitiesmentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

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“…found that the muscle and liver from the aged partner of the heterochronic pairs exhibited youthful levels of regeneration (Conboy et al., 2005). A similar “rejuvenating” effect of young blood has been demonstrated in other organs, including the spinal cord (Ruckh et al., 2012), heart (Loffredo et al., 2013), brain (Katsimpardi et al., 2014) (Villeda et al., 2014), β‐cells (Salpeter et al., 2013), and hair follicles (Keyes et al., 2013). Collectively, these observations suggest that exposure to a “young” environment could prevent or reverse age‐dependent decline in the function of critical organ systems.…”

Section: Introductionmentioning

confidence: 99%

Young plasma reverses age‐dependent alterations in hepatic function through the restoration of autophagy

et al. 2017

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SummaryRecent studies showing the therapeutic effect of young blood on aging‐associated deterioration of organs point to young blood as the solution for clinical problems related to old age. Given that defective autophagy has been implicated in aging and aging‐associated organ injuries, this study was designed to determine the effect of young blood on aging‐induced alterations in hepatic function and underlying mechanisms, with a focus on autophagy. Aged rats (22 months) were treated with pooled plasma (1 ml, intravenously) collected from young (3 months) or aged rats three times per week for 4 weeks, and 3‐methyladenine or wortmannin was used to inhibit young blood‐induced autophagy. Aging was associated with elevated levels of alanine transaminase and aspartate aminotransferase, lipofuscin accumulation, steatosis, fibrosis, and defective liver regeneration after partial hepatectomy, which were significantly attenuated by young plasma injections. Young plasma could also restore aging‐impaired autophagy activity. Inhibition of the young plasma‐restored autophagic activity abrogated the beneficial effect of young plasma against hepatic injury with aging. In vitro, young serum could protect old hepatocytes from senescence, and the antisenescence effect of young serum was abrogated by 3‐methyladenine, wortmannin, or small interfering RNA to autophagy‐related protein 7. Collectively, our data indicate that young plasma could ameliorate age‐dependent alterations in hepatic function partially via the restoration of autophagy.

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“…5 The hair follicle, which cycles through telogen (resting), anagen (growing), and catagen (regression) throughout the life of mammals, undergoes obvious age-related changes including hair loss. 6 The hair follicle contains hair-follicle-associated pluripotent (HAP) stem cells, [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] which may also deteriorate during aging.…”

Section: Introductionmentioning

confidence: 99%

Aging hair follicles rejuvenated by transplantation to a young subcutaneous environment

Cao

Kajiura

et al. 2016

Cell Cycle

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We demonstrate in the present study that young host mice rejuvenate aged hair follicles after transplantation. Young mice promote the hair shaft growth of transplanted old hair follicles, as well as young follicles, in contrast to old host mice, which did not support hair-shaft growth from transplanted old or young follicles. Nestin-expressing hair follicle-associated pluripotent (HAP) stem cells of transplanted old and young hair follicles remained active in young host nude mice. In contrast, the nestin-expressing HAP stem cells in young and old hair follicles transplanted to old nude mice were not as active as in young nude host mice. The present study shows that transplanted old hair follicles were rejuvenated by young host mice, suggesting that aging may be reversible.

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Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy

Cited by 803 publications

References 39 publications

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

Young plasma reverses age‐dependent alterations in hepatic function through the restoration of autophagy

Aging hair follicles rejuvenated by transplantation to a young subcutaneous environment

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