Candidate biomarkers of aging: Age-sensitive indices of immune and muscle function covary in genetically heterogeneous mice

被引:11
作者
Miller, RA
Bookstein, F
VanderMeulen, J
Engle, S
Kim, J
Mullins, L
Faulkner, J
机构
[1] UNIV MICHIGAN,SCH MED,DEPT PHYSIOL,ANN ARBOR,MI 48109
[2] UNIV MICHIGAN,INST GERONTOL,ANN ARBOR,MI 48109
[3] DEPT VET AFFAIRS MED CTR,ANN ARBOR,MI
来源
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES | 1997年 / 52卷 / 01期
关键词
D O I
10.1093/gerona/52A.1.B39
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
A longitudinal experiment was designed to test the hypothesis that individual mice differ in their aging rate and to validate candidate biomarkers proposed to measure the rate of aging. Mice were bred as the genetically heterogeneous progeny of a cross between CB6F1 mothers and C3D2F1 father. Half of the mice were fed ad libitum (AL group), and the other half were subjected to 60% calorie restriction (CR group). Each mouse was tested at about 9 months of age using age-sensitive tests of immune status, and then again at about 12 months of age using age-sensitive tests of muscle function. The data were then analyzed using the method of partial least squares to determine the combinations of test weights that maximize the covariance of the weighted sum of immune measures with the weighted sum of muscle function measures. Both AL and CR mice exhibited a statistically significant relation between the immune status tests and the muscle function tests. Maximal covariance was obtained with a set of weighting coefficients with our working hypothesis: mice with high levels of CD4 memory T cells (which increase with age) also had relatively low levels of muscle strength and endurance. Low strength was associated with low CD8 cells in the AL mice, with high numbers of CD8 memory cells in the CR mice and with low CD3 cells in both diet groups. The partial least squares method generates composite indices of immune status and muscle function that can be evaluated as biomarkers of aging rate in these mice. Further work will be needed to assess whether these tests predict either longevity or the trajectory of change in other age-sensitive molecular and physiological traits.
引用
收藏
页码:B39 / B47
页数:9
相关论文
共 44 条
[1]   BIOMARKERS OF AGING [J].
ADELMAN, RC .
EXPERIMENTAL GERONTOLOGY, 1987, 22 (04) :227-229
[2]  
[Anonymous], 1979, Multivariate analysis
[3]   AN APPARATUS TO MEASURE INVIVO BIOMECHANICAL BEHAVIOR OF DORSIFLEXORS AND PLANTARFLEXORS OF MOUSE ANKLE [J].
ASHTONMILLER, JA ;
HE, YD ;
KADHIRESAN, VA ;
MCCUBBREY, DA ;
FAULKNER, JA .
JOURNAL OF APPLIED PHYSIOLOGY, 1992, 72 (03) :1205-1211
[4]  
BAKER GT, 1988, EXP GERONTOL, V23, P223, DOI 10.1016/0531-5565(88)90025-3
[5]   ABSOLUTE PERIPHERAL-BLOOD LYMPHOCYTE COUNT AND SUBSEQUENT MORTALITY OF ELDERLY MEN - THE BALTIMORE LONGITUDINAL-STUDY OF AGING [J].
BENDER, BS ;
NAGEL, JE ;
ADLER, WH ;
ANDRES, R .
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 1986, 34 (09) :649-654
[6]   AGE-RELATED-CHANGES IN THE RELATIVE NUMBERS OF THY-1-BEARING AND LYT-2-BEARING PERIPHERAL-BLOOD LYMPHOCYTES IN MICE - A LONGITUDINAL APPROACH [J].
BOERSMA, WJA ;
STEINMEIER, FA ;
HAAIJMAN, JJ .
CELLULAR IMMUNOLOGY, 1985, 93 (02) :417-430
[7]  
Bookstein F.L., 1991, Morphometric tools for landmark data
[8]   MEASURING DOSE AND RESPONSE WITH MULTIVARIATE DATA USING PARTIAL LEAST-SQUARES TECHNIQUES [J].
BOOKSTEIN, FL ;
SAMPSON, PD ;
STREISSGUTH, AP ;
BARR, HM .
COMMUNICATIONS IN STATISTICS-THEORY AND METHODS, 1990, 19 (03) :765-804
[9]   CONTRACTILE PROPERTIES OF SKELETAL-MUSCLES FROM YOUNG, ADULT AND AGED MICE [J].
BROOKS, SV ;
FAULKNER, JA .
JOURNAL OF PHYSIOLOGY-LONDON, 1988, 404 :71-82
[10]  
BROOKS SV, 1994, MED SCI SPORT EXER, V26, P432