Stem CellsLifelong dietary intervention does not affect hematopoietic stem cell function

•Lifelong calorie restriction does not prevent stem cell aging.•Lifelong excessive calorie intake does not deteriorate stem cell function.•Aging is associated with increased inter-mouse variation in HSC pool size.

Hematopoietic stem cells (HSCs) undergo a profound functional decline during normal aging. Because caloric or dietary restriction has been shown to delay multiple aspects of the aging process in many species, we explored the consequences of lifelong caloric restriction, or conversely, lifelong excess caloric intake, on HSC numbers and function. Although caloric restriction prevented age-dependent increases in bone marrow cellularity, caloric restriction was not able to prevent functional decline of aged, long-term HSC functioning. A lifelong high-fat diet also did not affect HSC function. We conclude that lifelong caloric interventions fail to prevent or induce loss of age-associated HSC functioning.