Senescent cell accumulation & Research-based undergraduate education (2024)

Valentijn, F. (2022). . [Doctoral thesis 1 (Research UU / Graduation UU), UMC Utrecht]. Utrecht University. https://doi.org/10.33540/1121

Valentijn, Floris. / . Utrecht University, 2022. 250 p.

@phdthesis{4b53b0642de74cf9930f4afafe072d76,

title = "Senescent cell accumulation & Research-based undergraduate education",

abstract = "In part 1 of this thesis, the accelerated aging process of damaged kidney cells (“cellular senescence) in Chronic Kidney Disease (CKD), and targets for intervention are explored. Senescent kidney cells contribute to renal failure through scarring of kidney tissue and loss of function. We show that renal senescent cells accumulate in scarred kidney tissue in two groups of CKD patients: kidney transplant recipients and childhood cancer survivors (as complication of their treatment). From the reviewed literature and these observations, we conclude that CKD patients may benefit from elimination of renal senescent cells by so called “senotherapeutics”. We identified two important factors that contribute to senescent cell accumulation in the context of renal injury. First, aging magnifies senescent cell numbers after renal injury, suggesting that especially elderly may benefit from senotherapeutic therapy. Next, the molecule CCN2 plays an important role in renal senescent cell accumulation after kidney transplantation. Our findings suggest that an inhibitor of CCN2 is a promising senotherapeutic CKD treatment. For identifying other factors or targets for senescence in the kidney, we developed a screening tool using kidney cells that are in a state that resembles senescence.In part 2 of this thesis, implementation of a new translational medicine educational concept in which students conduct research into a real medically relevant problem, in biomedical bachelor education is evaluated. We show that bachelor students successfully design studies, acquire funding and execute laboratory-studies. Further, they develop important academic skills. This provides a new insight into the involvement of bachelor students in biomedical research.",

keywords = "Cellular Senescence, Chronic Kidney Disease, Kidney Fibrosis, Cellular Communication Network Factor 2, Research based undergraduate biomedical education, Translational medicine, Academic skills",

author = "Floris Valentijn",

year = "2022",

month = oct,

day = "18",

doi = "10.33540/1121",

language = "English",

publisher = "Utrecht University",

type = "Doctoral thesis 1 (Research UU / Graduation UU)",

school = "UMC Utrecht",

}

Valentijn, F 2022, '', UMC Utrecht. https://doi.org/10.33540/1121

/ Valentijn, Floris.
Utrecht University, 2022. 250 p.

Research output: Thesis › Doctoral thesis 1 (Research UU / Graduation UU)

TY - THES

T1 - Senescent cell accumulation & Research-based undergraduate education

AU - Valentijn, Floris

PY - 2022/10/18

Y1 - 2022/10/18

N2 - In part 1 of this thesis, the accelerated aging process of damaged kidney cells (“cellular senescence) in Chronic Kidney Disease (CKD), and targets for intervention are explored. Senescent kidney cells contribute to renal failure through scarring of kidney tissue and loss of function. We show that renal senescent cells accumulate in scarred kidney tissue in two groups of CKD patients: kidney transplant recipients and childhood cancer survivors (as complication of their treatment). From the reviewed literature and these observations, we conclude that CKD patients may benefit from elimination of renal senescent cells by so called “senotherapeutics”. We identified two important factors that contribute to senescent cell accumulation in the context of renal injury. First, aging magnifies senescent cell numbers after renal injury, suggesting that especially elderly may benefit from senotherapeutic therapy. Next, the molecule CCN2 plays an important role in renal senescent cell accumulation after kidney transplantation. Our findings suggest that an inhibitor of CCN2 is a promising senotherapeutic CKD treatment. For identifying other factors or targets for senescence in the kidney, we developed a screening tool using kidney cells that are in a state that resembles senescence.In part 2 of this thesis, implementation of a new translational medicine educational concept in which students conduct research into a real medically relevant problem, in biomedical bachelor education is evaluated. We show that bachelor students successfully design studies, acquire funding and execute laboratory-studies. Further, they develop important academic skills. This provides a new insight into the involvement of bachelor students in biomedical research.

AB - In part 1 of this thesis, the accelerated aging process of damaged kidney cells (“cellular senescence) in Chronic Kidney Disease (CKD), and targets for intervention are explored. Senescent kidney cells contribute to renal failure through scarring of kidney tissue and loss of function. We show that renal senescent cells accumulate in scarred kidney tissue in two groups of CKD patients: kidney transplant recipients and childhood cancer survivors (as complication of their treatment). From the reviewed literature and these observations, we conclude that CKD patients may benefit from elimination of renal senescent cells by so called “senotherapeutics”. We identified two important factors that contribute to senescent cell accumulation in the context of renal injury. First, aging magnifies senescent cell numbers after renal injury, suggesting that especially elderly may benefit from senotherapeutic therapy. Next, the molecule CCN2 plays an important role in renal senescent cell accumulation after kidney transplantation. Our findings suggest that an inhibitor of CCN2 is a promising senotherapeutic CKD treatment. For identifying other factors or targets for senescence in the kidney, we developed a screening tool using kidney cells that are in a state that resembles senescence.In part 2 of this thesis, implementation of a new translational medicine educational concept in which students conduct research into a real medically relevant problem, in biomedical bachelor education is evaluated. We show that bachelor students successfully design studies, acquire funding and execute laboratory-studies. Further, they develop important academic skills. This provides a new insight into the involvement of bachelor students in biomedical research.

KW - Cellular Senescence

KW - Chronic Kidney Disease

KW - Kidney Fibrosis

KW - Cellular Communication Network Factor 2

KW - Research based undergraduate biomedical education

KW - Translational medicine

KW - Academic skills

U2 - 10.33540/1121

DO - 10.33540/1121

M3 - Doctoral thesis 1 (Research UU / Graduation UU)

PB - Utrecht University

ER -

Valentijn F. . Utrecht University, 2022. 250 p. doi: 10.33540/1121