与其相反干细胞老化(stem cell aging)会导致脏器，组织的加龄变化。
干细胞能够接受由损伤部位发出的SDF-1讯号，前往损伤部位。一旦完成损伤部位的治疗，便会前往下一个发出讯号的损伤部位进行治疗。(打带跑现象)MSC: Messenchymal StemCell 间叶系干细胞
证明能延长健康寿命根据的论文Nature Communications 3, Article number: 608 doi:10.1038/ncomms1611,Published 03 January 2012
Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model
Mitra Lavasani, Andria R. Robinson, Aiping Lu, Minjung Song, Joseph M. Feduska, Bahar Ahani, Jeremy S. Tilstra, Chelsea H. Feldman, Paul D. Robbins, Laura J. Niedernhofer & Johnny Huard
With ageing, there is a loss of adult stem cell function. However, there is no direct evidence that this has a causal role in ageing-related decline. We tested this using muscle-derived stem/progenitor cells (MDSPCs) in a murine progeria model. Here we show that MDSPCs from old and progeroid mice are defective in proliferation and multilineage differentiation. Intraperitoneal administration of MDSPCs, isolated from young wild-type mice, to progeroid mice confer significant lifespan and healthspan extension. The transplanted MDSPCs improve degenerative changes and vascularization in tissues where donor cells are not detected, suggesting that their therapeutic effect may be mediated by secreted factor(s). Indeed, young wild-type-MDSPCs rescue proliferation and differentiation defects of aged MDSPCs when co-cultured. These results establish that adult stem/progenitor cell dysfunction contributes to ageing-related degeneration and suggests a therapeutic potential of post-natal stem cells to extend health.
STEM CELLS TRANSLATIONAL MEDICINE 2015;4:1–11
Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats
DAJEONG KIM, JANGBEEN KYUNG, DONGSUN PARK, EHN-KYOUNG CHOI, KWANG SEI KIM, KYUNGHA SHIN, HANGYOUNG LEE, IL SEOB SHIN, SUNG KEUN KANG, JEONG CHAN RA, YUN-BAE KIM
Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1〜3×10^6 cells per rat) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection.
Biochem Biophys Res Commun. 2012 Feb 10;418(2):313-8.
Identification of blood biomarkers of aging by transcript profiling of whole blood.
Nakamura S, Kawai K, Takeshita Y, Honda M, Takamura T, Kaneko S, Matoba R, Matsubara K.
Immunological changes that inevitably occur with aging are related to the onset of various diseases including autoimmune diseases, immunodeficiency, as well as other age-reflecting (AR) diseases. They are becoming serious problems in the global trend of longevity. To understand the AR changes, we searched for genes whose expression profiles in the whole peripheral blood change dramatically as a function of age using the Agilent whole human genome 44K microarray. After examining two cohorts consisting of 154 healthy people between age 23 and 77, we discovered 16 transcripts strongly and reproducibly correlated with age. Analysis using a publicly available gene expression dataset for a variety of human immune cells revealed that some of these transcripts were highly expressed in specific cell types whose number and function are known to change with age. This analysis shed light on the molecular mechanism of AR immunological system changes. Because of its simplicity, the assay system is expected to be useful for understanding individual health conditions.
Peters, M. J. et al. The transcriptional landscape of age in human peripheral blood. Nat. Commun. 6, 8570 (2015). Nakamura, S. et al. Identification of blood biomarkers of aging by transcript profiling of whole blood. Biochem. Biophys. Res. Commun. 418, 313・ (2012).
Hardie, D. L. et al. The stromal cell antigen CD248 (endosialin) is expressed on naive CD8+ human T cells and regulates proliferation. Immunology 133, 288・5 (2011).
Fagnoni, F. F. et al. Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. Blood 95, 2860・ (2000).
Watkins, N. A. et al. A HaemAtlas: characterizing gene expression in differentiated human blood cells. Blood 113, e1・ (2009).
Abbas, A. R. et al. Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data. Genes Immun. 6, 319・1 (2005).
Valle-Rios, R. et al. Isthmin 1 Is a Secreted Protein Expressed in Skin, Mucosal Tissues, and NK, NKT, and Th17 Cells. J. Interf. Cytokine Res. 34, 795・01 (2014).
Yuan, B. et al. Isthmin inhibits glioma growth through antiangiogenesis in vivo. J. Neurooncol. 109, 245・2 (2012). Xiang, W. et al. Isthmin is a novel secreted angiogenesis inhibitor that inhibits tumour growth in mice. J. Cell. Mol. Med. 15, 359・4 (2011).
Al Nimer, F. et al. Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light. PLoS One 10, e0132177 (2015). Celikbilek, A. et al. Elevated neurofilament light chain (NFL) mRNA levels in prediabetic peripheral neuropathy. Mol. Biol. Rep. 41, 4017・2 (2014).
Modvig, S. et al. Cerebrospinal fluid neurofilament light chain levels predict visual outcome after optic neuritis. Mult. Scler. (2015). doi:10.1177/1352458515599074
Weydt, P. et al. Neurofilaments levels as biomarkers in asymptomatic and symptomatic familial ALS. Ann. Neurol. (2015). doi:10.1002/ana.24552 de Jong, D. et al. CSF neurofilament proteins in the differential diagnosis of dementia. J. Neurol. Neurosurg. Psychiatry 78, 936・ (2007).
Skillback, T. et al. CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival. Neurology 83, 1945・3 (2014).4
Hallquist, N. A., Khoo, C. & Cousins, R. J. Lipopolysaccharide regulates cysteine-rich intestinal protein, a zinc-finger protein, in immune cells and plasma. J. Leukoc. Biol. 59, 172・ (1996).
Lanningham-Foster, L. et al. Overexpression of CRIP in transgenic mice alters cytokine patterns and the immune response. Am. J. Physiol. Endocrinol. Metab. 282, E1197・03 (2002).
Khoo, C., Hallquist, N. A., Samuelson, D. A. & Cousins, R. J. Differential expression of cysteine-rich intestinal protein in liver and intestine in CCl4-induced inflammation. Am. J. Physiol. 270, G613・ (1996).
Kahmann, L. et al. Zinc supplementation in the elderly reduces spontaneous inflammatory cytokine release and restores T cell functions. Rejuvenation Res. 11, 227・7 (2008).
Shankar, A. H. & Prasad, A. S. Zinc and immune function: the biological basis of altered resistance to infection. Am. J. Clin. Nutr. 68, 447S・63S (1998).
Hempe, J. M. & Cousins, R. J. Cysteine-rich intestinal protein binds zinc during transmucosal zinc transport. Proc. Natl. Acad. Sci. U. S. A. 88, 9671・ (1991).
Cousins, R. J. & Lanningham-Foster, L. Regulation of cysteine-rich intestinal protein, a zinc finger protein, by mediators of the immune response. J. Infect. Dis. 182 Suppl , S81・ (2000).
Wong, C. P. & Ho, E. Zinc and its role in age-related inflammation and immune dysfunction. Mol. Nutr. Food Res. 56, 77・7 (2012).
Damkier, H. H., Aalkjaer, C. & Praetorius, J. Na+-dependent HCO3- import by the slc4a10 gene product involves Cl- export. J Biol Chem 285, 26998・7007 (2010).
Jacobs, S. et al. Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability. Proc. Natl. Acad. Sci. U. S. A. 105, 311・16 (2008).
Gurnett, C. A. et al. Disruption of sodium bicarbonate transporter SLC4A10 in a patient with complex partial epilepsy and mental retardation. Arch. Neurol. 65, 550・ (2008).
Parker, M. D. & Boron, W. F. The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters. Physiol. Rev. 93, 803・59 (2013).
Parker, M. D. et al. Characterization of human SLC4A10 as an electroneutral Na/HCO3 cotransporter (NBCn2) with Cl- self-exchange activity. J. Biol. Chem. 283, 12777・8 (2008).
Pilling, L. C. et al. Gene expression markers of age-related inflammation in two human cohorts. Exp. Gerontol. 70, 37・5 (2015).
Farwell, W. R. & Taylor, E. N. Serum anion gap, bicarbonate and biomarkers of inflammation in healthy individuals in a national survey. CMAJ 182, 137・1 (2010).
Guo, L. et al. Common variants in the Na(+)-coupled bicarbonate transporter genes and salt sensitivity of blood pressure: the GenSalt study. J. Hum. Hypertens. (2015). doi:10.1038/jhh.2015.113