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Leukocyte TelomerE Dynamics, Gender, Menopause, Insulin Resistance and Survival

Award Number: R01AG030678
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2009
PERIOD OF PERFORMANCE END DATE: 06/30/2013

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Leukocyte TelomerE Dynamics, Gender, Menopause, Insulin Resistance and Survival - DESCRIPTION (provided by applicant): Leukocyte telomere length (LTL) is a complex genetic trait. LTL undergoes attrition with age and is associated with a host of aging related diseases and environmental conditions that diminish the human lifespan. Moreover, LTL forecasts mortality in the elderly. Cross-sectional studies have established that LTL is shorter in adult men than women and in individuals with cardiovascular diseases than in their healthy peers. LTL is also relatively short in individuals who are smokers, sedentary, overweight or of low socio-economic status. Collectively, such observations suggest that LTL is a biomarker of human aging. The two elements that contribute to leukocyte telomere dynamics are LTL and its age-dependent attrition rate. Whereas considerable information is available about LTL, little is known about the links between LTL attrition rate and aging related diseases. This project will resort to a longitudinal model in same-sex twin pairs to test the following central hypotheses: (i) Age-dependent leukocyte telomere attrition is faster in men than in women and in post-menopausal than pre- menopausal women; (ii) Leukocyte telomere attrition rate is faster under conditions of increased oxidative stress/inflammation, which are often associated with increased insulin resistance and diminished circulating IGF-1; (iii) In the elderly, LTL but not age-dependent telomere attrition rate is a predictor of mortality. This feature explains in part the longer lifespan of women than men; (iv) Age-dependent leukocyte telomere attrition is heritable. These hypotheses will be tested in two cohorts of Danish twins: the Geminakar Study and the Longitudinal Study of Aging Danish Twins (LSADT). The following are the project's specific aims: 1) Examine leukocyte telomere dynamics by Southern blots and real time-PCR measurements of telomeres, based on two occasions that span 10 years in adult twins (aged 18-63 at the baseline examination) and explore the roles of gender and menopause in telomere attrition and their links with obesity, insulin resistance, IGF-1 and indices of oxidative stress/inflammation; 2) Examine the links between leukocyte telomere dynamics and mortality/survival, based on leukocyte telomere measurements on two occasions, spanning 10 years, in elderly twins (at least 73 years old at the baseline examination). We will also explore the role of CMV and EBV infections in LTL dynamics. In a subset of the elderly, we will evaluate by flow FISH telomere signal intensities in CD8+ and CD4+ cells. Findings will refine our understanding of human telomere biology and its connections with aging and lifespan.


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: 2014 ( Subtotal = $0 )
2014	2013	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Aging Research	001	5	1/17/2014	NON-COMPETING CONTINUATION	$35,973
2014	2012	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Aging Research	000	6	1/16/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$35,973
														Subtotal = $0

Issue Date FY: 2013 ( Subtotal = $371,715 )
2013	2013	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Aging Research	001	5	5/15/2013	NON-COMPETING CONTINUATION	$15,986
2013	2013	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Aging Research	000	5	1/25/2013	NON-COMPETING CONTINUATION	$319,756
2013	2013	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Aging Research	004	5	1/17/2014	NON-COMPETING CONTINUATION	$35,973
2013	2013	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Aging Research	002	5	8/9/2013	NON-COMPETING CONTINUATION	-$94,681
2013	2012	Rutgers, The State Univ Biomedical & HEALTH Sciences	65 Davidson Road	Piscataway	NJ	08554		USA	Aging Research	003	6	8/12/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$94,681
														Subtotal = $371,715

Issue Date FY: 2012 ( Subtotal = $394,846 )
2012	2012	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Aging Research	000	4	2/2/2012	NON-COMPETING CONTINUATION	$394,846
														Subtotal = $394,846

Issue Date FY: 2011 ( Subtotal = $470,550 )
2011	2011	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Aging Research	001	3	6/20/2011	NON-COMPETING CONTINUATION	$29,944
2011	2011	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Aging Research	000	3	1/31/2011	NON-COMPETING CONTINUATION	$440,606
														Subtotal = $470,550

Issue Date FY: 2010 ( Subtotal = $479,095 )
2010	2010	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Aging Research	000	2	3/19/2010	NON-COMPETING CONTINUATION	$479,095
														Subtotal = $479,095

Issue Date FY: 2009 ( Subtotal = $505,545 )
2009	2009	UNIVERSITY OF MEDICINE & DENTISTRY OF NEW JERSEY	POST OFFICE BOX 2100	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Aging Research	000	1	2/5/2009	NEW	$505,545
														Subtotal = $505,545

Grand Total All Awards = $2,221,751

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Leukocyte TelomerE Dynamics, Gender, Menopause, Insulin Resistance and Survival

Award Number: R01AG030678

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/15/2009

PERIOD OF PERFORMANCE END DATE: 06/30/2013

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