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ROLE OF ION CHANNELS IN SARCOPENIA

Award Number: R01AG018755
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/15/2001
PERIOD OF PERFORMANCE END DATE: 02/28/2006

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ROLE OF ION CHANNELS IN SARCOPENIA - DESCRIPTION: (Verbatim from the application) One of the most serious problems of mobility impairment is the tendency of old adults to fall. Falls account for almost 90 percent of all fractures in the elderly. The limitations in performing activities of daily living and falls are undoubtedly associated with alterations on postural muscles. Postural muscles are concerned with steadying a segment of the body on another in standing. This muscle subgroup exhibits a high content of slow muscle fibers. In the soleus muscle of many adult mammals the proportion of this type of fiber approaches 100 percent (more than 80 percent in humans). Although the crucial role in posture, the mechanical properties and the molecular mechanisms involved in single intact slow fibers contraction in the elderly or animal models of aging have not been explored. Unfortunately the information about age-related changes in fast-twitch fibers cannot be extrapolated to slow fibers due to substantial physiological, structural and biochemical differences between the two fiber subtypes. The hypothesis of this proposal is that the decrease in dihydropyridine receptor (DHPR) gene expression in type-1 fibers results in a decline in skeletal muscle force with aging. A lower number of DHPR renders a significant number of RyR1 unlinked and unable to be activated by sarcolemmal depolarization, leading to a substantial decline in sarcopasmic reticulum Ca2+influx and contractile force in aging slow-twitch muscles. This hypothesis will be assessed using the following specific aims: (1) To determine whether the decline in single skeletal muscle fiber contractility is associated with alterations in peak intracellular calcium concentration in single slow-twitch (type 1) muscle fibers from young (7months), middle-age (14), and old (28) C57BL/6 mice. (2) To establish whether the age-related impairment in type-1 fiber contractility results from a reduction in sarcoplasmic reticulum Ca2+ release. (3) To determine whether the age-related decline in functionally monitored DHPR is associated with a decrease in DHPR gene expression measured in the same type-1 single muscle fiber or whole soleus muscle, and (4) To define whether alterations in DHPR and/or RyR1 expression in slow muscle from aging mice results from a decline in nuclear transcriptional activity of DHPR alpha1, alpha2, beta, gamma and delta subunits and/orRyR1 DNA.


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: 2005 ( Subtotal = $252,000 )
2005	2005	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	5	4/14/2005	NON-COMPETING CONTINUATION	$252,000
														Subtotal = $252,000

Issue Date FY: 2004 ( Subtotal = $252,000 )
2004	2004	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	4	2/16/2004	NON-COMPETING CONTINUATION	$252,000
														Subtotal = $252,000

Issue Date FY: 2003 ( Subtotal = $252,000 )
2003	2003	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Aging Research	000	3		NON-COMPETING CONTINUATION	$252,000
														Subtotal = $252,000

Issue Date FY: 2002 ( Subtotal = $245,802 )
2002	2002	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Aging Research	000	2	1/30/2002	NON-COMPETING CONTINUATION	$245,802
														Subtotal = $245,802

Issue Date FY: 2001 ( Subtotal = $246,605 )
2001	2001	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Aging Research	000	1	3/6/2001	NEW	$246,605
														Subtotal = $246,605

Grand Total All Awards = $1,248,407

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ROLE OF ION CHANNELS IN SARCOPENIA

Award Number: R01AG018755

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/15/2001

PERIOD OF PERFORMANCE END DATE: 02/28/2006

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