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IGF-1, oxidative stress and telomere dynamics in cultured human somatic cells

Award Number: F30AG032858
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2008
PERIOD OF PERFORMANCE END DATE: 06/30/2013

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IGF-1, oxidative stress and telomere dynamics in cultured human somatic cells - DESCRIPTION (provided by applicant): The primary objective of this project is to study mechanisms by which the insulin-like growth factor 1 (IGF-1) affects oxidative stress, telomere dynamics and senescence in human somatic cells. IGF-1 mediated stimulation of cell proliferation is crucial for maintenance and repair of somatic tissues. However, this effect is often associated with the shuttling of FOXO transcription factors out of the nucleus and the downregulation of antioxidative enzymes. IGF-1 also stimulates the nitric oxide synthase (NOS), increasing production of nitric oxide (NO), an antioxidant and antiproliferative agent. The overall effect of IGF-1 would thus depend on a balance between the FOXO and NOS pathways. The central hypothesis of this proposal is that in most human tissues the IGF-1 mediated effect is tilted towards the FOXO pathway, i.e., proliferation and increased oxidative stress. However, in the human vascular endothelium, the effect of IGF-1 is tilted towards endothelial NOS (eNOS). In this way, the integrative effect of IGF-1 would serve the maintenance and repair needs of the soma, while attenuating the effect of oxidative stress on the vasculature. As telomere shortening registers the proliferative history and accruing burden of oxidative stress, the diverse effects of IGF-1 would be largely expressed in telomere dynamics of different cell types. This hypothesis will be tested through two aims: one, to evaluate mechanisms by which IGF-1 influences telomere dynamics in cultured skin fibroblasts by examining the effects of IGF-1 on proliferation/senescence, telomeric attrition, FOXO transcription factors, antioxidative capacity, eNOS expression and NO production; and two, to evaluate IGF-1's effect in cultured human umbilical vein endothelial cells, as per aim 1. Findings will provide a comprehensive account of the mechanisms by which IGF-1 impacts proliferation, oxidative stress, telomere dynamics and senescence in human somatic cells. These interrelated mechanisms could account for the often conflicting conclusions about the role of IGF-1 in aging and longevity of lower organisms (the worm, fly), short-lived mammals (mouse) and humans. This project will provide mechanistic insight as to how a key growth factor acts on human cells, which is essential for understanding its role in the biology of human aging and in aging related disorders. Such information will be instrumental in designing preventive and therapeutic modalities to fight aging related diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2017 ( Subtotal = -$3,330 )
2017	2012	UNIVERSITY OF MEDICINE AND DENTISTRY OF NJ (INC)							Aging Research	000	5	12/14/2016	NON-COMPETING CONTINUATION	-$3,330
														Subtotal = -$3,330

Issue Date FY: 2012 ( Subtotal = $41,740 )
2012	2012	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07107	ESSEX	USA	Aging Research	000	5	4/24/2012	NON-COMPETING CONTINUATION	$41,740
														Subtotal = $41,740

Issue Date FY: 2011 ( Subtotal = $42,313 )
2011	2011	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07107	ESSEX	USA	Aging Research	000	4	5/19/2011	NON-COMPETING CONTINUATION	$42,313
														Subtotal = $42,313

Issue Date FY: 2010 ( Subtotal = $30,131 )
2010	2010	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07107	ESSEX	USA	Aging Research	000	3	5/31/2010	NON-COMPETING CONTINUATION	$30,131
														Subtotal = $30,131

Issue Date FY: 2009 ( Subtotal = $29,879 )
2009	2009	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07107	ESSEX	USA	Aging Research	000	2	6/25/2009	NON-COMPETING CONTINUATION	$29,879
														Subtotal = $29,879

Issue Date FY: 2008 ( Subtotal = $29,675 )
2008	2008	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	65 BERGEN STREET	NEWARK	NJ	07101	ESSEX	USA	Aging Research	000	1	6/20/2008	NEW	$29,675
														Subtotal = $29,675

Grand Total All Awards = $170,408

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IGF-1, oxidative stress and telomere dynamics in cultured human somatic cells

Award Number: F30AG032858

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2008

PERIOD OF PERFORMANCE END DATE: 06/30/2013

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