title: Calorie Restriction Attenuates Terminal Differentiation of Immune Cells.
abstract: Immune senescence is a natural consequence of aging and may contribute to frailty and loss of homeostasis in later life. Calorie restriction increases healthy life-span in C57BL/6J (but not DBA/2J) mice, but whether this is related to preservation of immune function, and how it interacts with aging, is unclear. We compared phenotypic and functional characteristics of natural killer (NK) cells and T cells, across the lifespan, of calorie-restricted (CR) and control C57BL/6 and DBA/2 mice. Calorie restriction preserves a naïve T cell phenotype and an immature NK cell phenotype as mice age. The splenic T cell populations of CR mice had higher proportions of CD11a-CD44locells, lower expression of TRAIL, KLRG1, and CXCR3, and higher expression of CD127, compared to control mice. Similarly, splenic NK cells from CR mice had higher proportions of less differentiated CD11b-CD27+cells and correspondingly lower proportions of highly differentiated CD11b+CD27-NK cells. Within each of these subsets, cells from CR mice had higher expression of CD127, CD25, TRAIL, NKG2A/C/E, and CXCR3 and lower expression of KLRG1 and Ly49 receptors compared to controls. The effects of calorie restriction on lymphoid cell populations in lung, liver, and lymph nodes were identical to those seen in the spleen, indicating that this is a system-wide effect. The impact of calorie restriction on NK cell and T cell maturation is much more profound than the effect of aging and, indeed, calorie restriction attenuates these age-associated changes. Importantly, the effects of calorie restriction on lymphocyte maturation were more marked in C57BL/6 than in DBA/2J mice indicating that delayed lymphocyte maturation correlates with extended lifespan. These findings have implications for understanding the interaction between nutritional status, immunity, and healthy lifespan in aging populations.
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine , London , UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: White
authors.affiliation: UCL Institute of Healthy Ageing, University College London , London , UK.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Beaver
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine , London , UK.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Goodier
authors.affiliation: Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine , London , UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Bottomley
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine , London , UK.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Nielsen
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine , London , UK.
authors.forename: Asia-Sophia F M
authors.initials: AF
authors.lastname: Wolf
authors.affiliation: Dubowitz Neuromuscular Centre, Developmental Neurosciences Programme, Molecular Neurosciences Section, Institute of Child Health, University College London , London , UK.
authors.forename: Luisa
authors.initials: L
authors.lastname: Boldrin
authors.affiliation: Dubowitz Neuromuscular Centre, Developmental Neurosciences Programme, Molecular Neurosciences Section, Institute of Child Health, University College London , London , UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Whitmore
authors.affiliation: Dubowitz Neuromuscular Centre, Developmental Neurosciences Programme, Molecular Neurosciences Section, Institute of Child Health, University College London , London , UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Morgan
authors.affiliation: UCL Institute of Healthy Ageing, University College London , London , UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Pearce
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine , London , UK.
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
keywords: T cell; aging; calorie restriction; differentiation; maturation; natural killer cell