Positive effects of prolonged caloric restriction on the population of very small embryonic-like stem cells – hematopoietic and ovarian implications

Abstract

BackgroundLow calorie intake, or calorie restriction (CR) without malnutrition, has been demonstrated in several animal species, including mice, to increase both median and maximum lifespan as well as delay reproductive senescence. Our previous work demonstrated a positive correlation between life span and the number of very small embryonic-like stem cells (VSELs) in long living Laron dwarf mice. These animals have very low levels of circulating insulin-like growth factor 1 (IGF-1) in peripheral blood (PB), maintain higher numbers of hematopoietic stem cells (HSPCs) in bone marrow (BM), and display prolonged fecundity compared with wild type littermates. Since CR lowers the level of IGF-1 in PB, we become interested in the effect of CR on the number of VSELs and HSPCs in BM as well as on the morphology of ovaries and testes.MethodsIn our studies four-week-old female and male mice were subjected to CR by employing an alternate-day ad libitum feeding diet for a period of 9 months.ResultsWe observed that mice on CR had a higher number of BM-residing VSELs than control mice fed ad libitum. These changes correlated with higher numbers of HSPCs in BM, spleen, and peripheral blood (PB) as well as with an increase in the number of primordial and primary follicles in ovaries. At the same time, however, no changes were observed in the testes of mice under CR.ConclusionWe conclude that CR positively affects the pool of VSELs in adult tissues and explains the positive effect of CR on longevity.

A Novel View of the Adult Stem Cell Compartment From the Perspective of a Quiescent Population of Very Small Embryonic-Like Stem Cells

“…As recently reported, the number of VSELs in murine BM increases in vivo in response to regular physical activity and prolonged caloric restriction 116,117 . On the other hand, highly quiescent VSELs in murine BM may enter the cell cycle, as confirmed by bromodeoxyuridine (BrdU) accumulation in these cells after administration of sex hormones (SexHs, such as follicle stimulating factor [FSH] or luteinizing hormone [LH]) or erythropoietin (EpO) 88,89 .…”

Very small embryonic-like stem cells as a novel developmental concept and the hierarchy of the stem cell compartment

“…Based on these findings, we tested the effect of prolonged exercise and calorie restriction [97] of VSELs in adult mice and observed that both of these approaches have beneficial effects on the number of these cells compared with control animals that are fed ad libitum and do not exercise. These observations in experimental mice may have important implications for humans.…”

Number and density of equine preantral follicles in different ovarian histological section thicknesses

“…The histological section thickness can influence the evaluation of preantral follicle population. Studies in this area used different section thicknesses (e.g., 3 mm: mice [14]; 5 mm: ovine [15], equine [16]; 6 mm: ovine [17]; 7 mm: caprine [18], bovine [19]; or 10 mm: women [20], equine [8][9][10]). These studies reported the lack of a standardization for histological section thickness preparations even within the same species (e.g., ovine [21,22]).…”