Aged Mice Repeatedly Injected with Plasma from Young Mice: A Survival Study

Shytikov, Dmytro; Balva, Olexiy; Debonneuil, Edouard; Glukhovskiy, Pavel; Pishel, Iryna

doi:10.1089/biores.2014.0043

Cited by 23 publications

(21 citation statements)

References 29 publications

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“…Further, aged mice given young plasma showed improvement in age-related decline in hippocampus-dependent learning and memory [67]. However, 10-12-month-old CBA/Ca female mice (a strain with normal longevity) injected weekly with young plasma did not show increased lifespan [68]. Most recently, using a blood-exchange device to exchange blood between young and old mice once, old mice exhibited improved hepatogenesis and response to muscle injury while young animals showed no difference in injury response and worsened hepatogenesis.…”

Section: Box 3 Anti-aging Effects Of Young Bloodmentioning

confidence: 97%

The Business of Anti-Aging Science

Magalhães

Stevens

Thornton

2017

Trends in Biotechnology

138

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Age-related conditions are the leading causes of death and health-care costs. Reducing the rate of aging would have enormous medical and financial benefits. Myriad genes and pathways are known to regulate aging in model organisms, fostering a new crop of anti-aging companies. Approaches range from drug discovery efforts to big-data methods and direct-to-consumer (DTC) strategies. Challenges and pitfalls of commercialization include reliance on findings from short-lived model organisms, poor biological understanding of aging, and hurdles in performing clinical trials for aging. A large number of potential aging-associated interventions and targets exist, but given the long validation times only a small fraction can be explored for clinical applications. If even one company succeeds, however, the impact will be huge.

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Section: Box 3 Anti-aging Effects Of Young Bloodmentioning

confidence: 97%

The Business of Anti-Aging Science

Magalhães

Stevens

Thornton

2017

Trends in Biotechnology

138

View full text Add to dashboard Cite

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“…This was shown with heterochronic parabiosis mouse models 4 , 5 , in which young and old mice share their circulatory system. However, a long-term study with repeated injections of plasma from young to old mice did not show a significant effect 6 .…”

Section: Introductionmentioning

confidence: 82%

“…In the context of young blood rejuvenation therapy, improved tissue homeostasis was found in a mouse parabiosis model in response to 5-weeks treatments 4 , 5 . If the simple transfer of blood had an impact on tissue homeostasis, which is controversial 6 , 9 , this would open the possibility to apply young blood therapy to humans. According to the model results, the treatment schedule identified in mice with positive effect on tissue homeostasis cannot be transferred to the human case and would not induce the same degree of rejuvenation, in particular, in low turnover organs like the brain.…”

Section: Discussionmentioning

confidence: 99%

Estimation of the cancer risk induced by therapies targeting stem cell replication and treatment recommendations

Meyer‐Hermann

2018

Sci Rep

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Rejuvenation of stem cell activity might increase life expectancy by prolonging functionality of organs. Higher stem cell replication rates also bear the risk of cancer. The extent of this risk is not known. While it is difficult to evaluate this cancer risk in experiments, it can be estimated using a mathematical model for tissue homeostasis by stem cell replication and associated cancer risk. The model recapitulates the observation that treatments targeting stem cell replication can induce a substantial delay of organ failure. The model predicts that the cancer risk is minor under particular conditions. It depends on the assumed implications for cell damage repair during treatment. The benefit of rejuvenation therapy and its impact on cancer risk depend on the biological age at the time of treatment and on the overall cell turnover rate of the organs. Different organs have to be considered separately in the planning of systemic treatments. In recent years, the transfer of blood from young to old individuals was shown to bear the potential of rejuvenation of stem cell activity. In this context, the model predicts that the treatment schedule is critical for success and that schedules successful in animal experiments are not transferable to humans. Guidelines for successful protocols are proposed. The model presented here may be used as a guidance for the development of stem cell rejuvenation treatment protocols and the identification of critical parameters for cancer risk.

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“…A limitation in our study is that parabiosis is only shown here as a pro-aging phenomenon, and a proteomics analysis will be applied in our next study to explore the specific pro-aging factors in old mice that are responsible for the effects found on young cartilage. To investigate the possible involvement of soluble factors, parabiosis alone would not be adequate, whereas plasma transfusions [ 29 ] could be used to study soluble factors due to removal of the cellular components. Future studies will be required to explore the use of various models (other than parabiosis) to elucidate the pro-aging factors that cause the observed effects on young cartilage.…”

Section: Discussionmentioning

confidence: 99%

Impairment of chondrocyte proliferation after exposure of young murine cartilage to an aged systemic environment in a heterochronic parabiosis model

Wei

Geng³

et al. 2018

Swiss Med Wkly

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SummaryAIM:The aim of this study was to investigate whether an aged systemic environment could impair young cartilage tissue in mice.METHODS:Mice differing in age were randomly divided into three groups. Group 1 was the experimental group (Y/O group) consisting of the heterochronic parabiosis model (2-month-old/12-month-old, young/old). Group 2 was the surgical control group (Y/Y group) with the isochronic parabiosis model (2-month-old/2-month-old, young/young). Group 3 consisted of the ageing control mice (2-month-old alone, Y group). Young knee cartilages collected from all three groups at 4 months after surgery were compared. Fluorescence molecular tomography (FMT) was used to confirm whether the two mice in parabiosis shared a common blood circulation at 2 weeks after surgery. The knee joints of young mice were examined radiologically at 4 months after surgery. Histological scoring was assigned to grade the severity of osteoarthritis (OA). Immunohistochemistry and quantitative reverse transcription polymerase chain reaction were used to evaluate OA-related protein expression and gene expression, and chondrocyte proliferation was determined with EdU staining.RESULTS:FMT imaging confirmed cross-circulation in the parabiotic pairs. The percentage of EdU-positive chondrocytes in young mice from the Y/O group was significantly lower compared with those of the Y/Y and Y groups (p <0.05 for both). There was no statistically significant difference in the mRNA expression of collagen type II (Col2), collagen type X (Col10), and matrix metalloproteinase 13 (MMP13) among the three groups (P>0.05), but expression of sex-determining region Y box 9 (Sox9) mRNA in young cartilage from the Y/O group was markedly attenuated compared to those in the Y/Y and Y groups (p <0.05 for both). In the Y/O group, mRNA expression of runt-related transcription factor 2 (Runx2) in young cartilage was significantly increased compared to the Y/Y and Y groups (p <0.05 for both). The changes in Col2, Col10, MMP13, Runx2 and Sox9 at the protein level mimicked the alterations found at the mRNA level. Loss of cartilage proteoglycan in young mice from the Y/O group was significantly greater compared to the Y/Y and Y groups (p <0.05 for both), despite the lack of significant difference among the three groups in OARIS and osteophytosis scores.CONCLUSION:Heterochronic parabiosis exerts a negative effect on chondrocyte proliferation in the knee cartilage of young mice.

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Aged Mice Repeatedly Injected with Plasma from Young Mice: A Survival Study

Cited by 23 publications

References 29 publications

The Business of Anti-Aging Science

The Business of Anti-Aging Science

Estimation of the cancer risk induced by therapies targeting stem cell replication and treatment recommendations

Impairment of chondrocyte proliferation after exposure of young murine cartilage to an aged systemic environment in a heterochronic parabiosis model

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