Grymula Katarzyna, Piotrowska Katarzyna, Słuczanowska-Głąbowska Sylwia, Mierzejewska Katarzyna, Tarnowski Maciej, Tkacz Marta, Poniewierska-Baran Agata, Pędziwiatr Daniel, Suszyńska Ewa, Laszczyńska Maria, Ratajczak Mariusz Z
Department of Physiology at Pomeranian, Medical University, Szczecin, Poland.
Department of Histology and Developmental Biology, Pomeranian Medical University, Szczecin, Poland.
J Ovarian Res. 2014 Jun 21;7:68. doi: 10.1186/1757-2215-7-68. eCollection 2014.
Low 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.
In 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.
We 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.
We conclude that CR positively affects the pool of VSELs in adult tissues and explains the positive effect of CR on longevity.
低热量摄入，即无营养不良的热量限制（CR），已在包括小鼠在内的几种动物物种中得到证实，可延长平均寿命和最大寿命，并延缓生殖衰老。我们之前的研究表明，长寿的拉龙侏儒小鼠的寿命与非常小的胚胎样干细胞（VSELs）数量之间存在正相关。这些动物外周血（PB）中循环胰岛素样生长因子1（IGF-1）水平极低，骨髓（BM）中造血干细胞（HSPCs）数量维持较高水平，与野生型同窝小鼠相比，其繁殖力延长。由于CR会降低PB中IGF-1的水平，我们开始关注CR对BM中VSELs和HSPCs数量以及卵巢和睾丸形态的影响。
在我们的研究中，四周龄的雌性和雄性小鼠采用隔日自由采食饮食进行9个月的CR。
我们观察到，进行CR的小鼠BM中VSELs数量高于自由采食的对照小鼠。这些变化与BM、脾脏和外周血（PB）中HSPCs数量增加以及卵巢中原始卵泡和初级卵泡数量增加相关。然而，同时在进行CR的小鼠睾丸中未观察到变化。
我们得出结论，CR对成年组织中VSELs池有积极影响，并解释了CR对长寿的积极作用。
