Body weight, hormones and T cell subsets as predictors of life span in genetically heterogeneous mice.
Previous studies have shown that T cell subset levels, early life body weight, and levels of leptin and thyroid hormones can each serve, independently, as predictors of life span in populations of genetically heterogeneous mice. New data now confirm, in a replicate cohort, that T cell subset patterns predict longevity, and show that they can do so when measured in mice as young as 8 months of age. Individual T cell subsets, as well as composite indices that combine data from two or more T cell measures at 8 or 18 months, can be combined with 3- and 9-month body weight data to provide better prediction of life span than either immune or weight measures alone. Mice whose immune and weight measures are both in the lowest quartile have mean and maximal life spans that are 18% and 16-25% higher, respectively, than mice in the opposite quartiles for both traits. Thyroxine levels measured at 4 months lead to further improvement over models that combine weight and immune data only. A genome scan provided evidence for loci on chromosomes 2, 12, 13, and 17 that modulate age-sensitive T cell subset patterns at both 8 and 18 months of age. These data show that late-life mortality risks are influenced to a measurable degree by factors that modulate growth trajectory and hormone and immune status in the first third of the life span, and provide clues as to which early life systems deserve further scrutiny as potential mediators of late life disease risk.
Harper
James M
JM
Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Galecki
Andrzej T
AT
Burke
David T
DT
Miller
Richard A
RA
D000375:Aging / Q000276:immunology / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000276:immunology / Q000502:physiology*; D002875:Chromosomes / Q000276:immunology / Q000502:physiology*; D020738:Leptin / Q000378:metabolism*; D008017:Life Expectancy; D008136:Longevity / Q000276:immunology / Q000502:physiology*; D051379:Mice; D011237:Predictive Value of Tests; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology*; D013963:Thyroid Hormones / Q000378:metabolism*
D020738:Leptin; D013963:Thyroid Hormones