Agotamiento de las células madre hematopoyéticas y productos finales de la glicación avanzada en la anemia inexplicada de la persona mayor / Hematopoietic stem cell exhaustion and advanced glycation end-products in the unexplained anemia of the elderly

Introducción. En occidente, más del 10% de las personas mayores de 65 años padecen anemia. Hasta en un tercio de los mismos esta es inexplicada. La anemia inexplicada de la persona mayor (AI) se considera un diagnóstico de exclusión, sin que exista un consenso en los criterios para su abordaje clínico o experimental. En estudios en animales y humanos se ha evidenciado que existe un vínculo entre envejecimiento y anemia. Objetivos. Conocer si existe evidencia en la literatura que soporte como causa de AI al agotamiento de células madre hematopoyéticas (CMH) y al acúmulo de productos finales de la glicación avanzada (AGE). Método. Tras una revisión exhaustiva de la literatura se seleccionaron 32 trabajos de investigación (28 para agotamiento de CMH y 4 para AGE). Se vincularon sus conclusiones a los mecanismos y efectos tanto del agotamiento de CMH como del acúmulo de AGE sobre el envejecimiento y la anemia. Resultados. Únicamente 3 trabajos relacionaron la AI con el agotamiento de CMH y 2 de ellos difirieron en sus conclusiones, el tercero difirió en el tipo de estudio. Existe relación del incremento y acúmulo de AGE con anemia en la persona mayor. Conclusión. Existe evidencia en la literatura que vincula los mecanismos moleculares y celulares del envejecimiento con el agotamiento de CMH y el acúmulo de AGE, también existe evidencia de que ambas entidades condicionan anemia relacionada a la edad en animales y humanos. Hay una pobre evidencia en la literatura que determine una relación entre envejecimiento y AI (AU)

Introduction. More than 10% of the aged 65 years and over in the western world suffers anemia and in one third of them the cause of the anemia remains obscure. The unexplained anemia of the elderly (UAE) is considered an exclusion diagnosis, without the existence of a clear consensus to its clinical or experimental approach. There is an association between aging and anemia in studies performed in animals and in humans. Objectives. To determine if there is evidence in the literature that supports hematopoietic stem cells (HSC) exhaustion and the advanced glycation end-products (AGE's) as a cause of UAE. Method. A total of 32 combined texts (28 for HSC exhaustion and 4 for AGEs) were selected after an intensive review. Conclusions were associated with causes and effects of the HSC exhaustion and circulating AGE's over aging and anemia. Results. Only three works try to establish an association between UAE and HSC exhaustion, two of them disagreed in their conclusions, with the third one differing in the type of study. There is a relationship between anemia and AGEs increase and accumulation. Conclusions. There is evidence in the literature that links the aging molecular and cellular mechanisms with the HSC exhaustion and the increase of AGE's. Furthermore; there is some evidence that both conditions determine the emergence of anemia associated with age in animals and in humans. There is little evidence in the literature to clarify the relationship between aging and UAE (AU)

Standardizing the immunological measurement of advanced glycation endproducts using normal human serum.

Advanced glycation endproducts (AGEs) have been linked to many sequelae of diabetes, renal disease and aging. To detect AGE levels in human tissues and blood samples, a competitive enzyme-linked immunosorbent assay (ELISA) has been widely used. As no consensus or standard research method for the quantitation of AGEs currently exists, nor a universally defined AGE unit available, the comparative quantitation of AGEs between research laboratories is problematic and restricts the usefulness of interlaboratory clinical data. By comparing the cross-reactivities of five different anti-AGE antisera with five different in vitro AGE-modified proteins, we found that the immunological recognition of AGEs by competitive ELISA is both AGE-carrier protein- and anti-AGE antibody-dependent. This suggests that in vitro AGE-modified proteins might not be appropriate standards for AGEs that occur naturally in vivo. Based on our observation that serum AGE levels in the normal human population are consistently within a narrow range and several folds lower than in diabetics, we propose a method to standardize AGE units against normal human serum (NHS). In this new method, one AGE unit is defined as the inhibition that results from 1:5 diluted NHS in the competitive AGE-ELISA; thus the AGE value in NHS is 5 units/ml. This NHS method requires a competitive AGE-ELISA with reasonable sensitivity such that 1:5 NHS produces a 25 to 40% inhibition of anti-AGE antibody binding to immobilized AGE-proteins. By using this standardized method we found that the AGE levels in normal human serum (5.0 +/- 2.2 units/ml; mean +/- SD, n = 34) fit a normal distribution (chi 2-test, p < 0.01), and the serum AGE levels in diabetic patients (20.3 +/- 3.8 units/ml, n = 7) are significantly higher than that of the normal population (p < 0.0001). Since AGE units can now be defined against a universally available standard, NHS, the results of quantitative AGE measurements using this method should be comparable between assays and between different laboratories. Taken together, standardizing the AGE-ELISA protocol as described here provides a simple and quantitative method that should facilitate the expanded application of clinical AGE data.