成人大脑皮质老化形态学改变的MRI研究

目的 探讨成人大脑正常衰老过程中大脑皮质体积、厚度及表面积改变的区域性差异及侧化差异MRI的表现。方法 采用前瞻性研究。2017年9月—2018年1月山东省立医院影像科及寿光市人民医院CT磁共振室招募18~85岁右利手汉族健康成年志愿者109人,其中男性56人、女性53人,年龄(53.13±15.61)岁,均行3.0 T MRI颅脑扫描原始数据。使用FreeSurfer脑成像软件分析,获取左右大脑半球、各脑叶的感兴趣区脑皮质的体积、厚度及表面积的具体数值并进行标准化处理,分析其与年龄的相关关系,以及大脑皮质老化的区域性差异及侧化差异。结果 线性回归分析显示,大脑皮质体积、厚度及表面积随年龄增长而下降(P＜0.01),表现出与年龄相关的皮质体积减少较多的区域为海马旁回、额下回岛盖部、额中回、额下回三角部、舌回、颞中回(最大为-0.653%/岁,P＜0.01),皮质厚度减少较多的区域主要在颞上回、后扣带回、额中回、外眶额回、顶下缘角回、颞极、海马旁回(最大-0.009 mm/岁,P<0.01),皮质表面积减少较多的区域主要是在海马旁回、舌回、颞下回、额中回、额下回岛盖部(最大-0.402%/岁,P＜ 0.01)。大脑左右半球皮质体积年龄效应不对称的区域为额上回、额下回岛盖部及三角部、中眶额回、额极、顶下缘角回、缘上回、梭状回、颞极、海马旁回、前扣带回、内嗅皮层(P＜0.05),皮质厚度年龄效应不对称的区域为额上回、额下回岛盖部、中眶额回、楔叶、颞下回、颞极、前扣带回、后扣带回(P＜0.05),皮质表面积年龄效应不对称的区域为额上回、额中回、额下回岛盖部及三角部、中眶额回、额极、顶下缘角回、缘上回、梭状回、颞极、海马旁回、前扣带回、后扣带回、内嗅皮层(P＜0.05)。结论 在人脑的正常老化过程中,大脑皮质体积、厚度及表面积与年龄呈现线性负相关性改变,不同脑区皮质与年龄呈不同程度的线性负相关关系,部分脑回皮质的年龄效应存在侧化差异,皮质体积、厚度、表面积三个形态学指标是相互关联的。     

Sensory response properties of pyramidal tract neurons in the precentral motor cortex and postcentral gyrus of the rhesus monkey

Summary Pyramidal tract neurons (PTNs) were identified in precentral motor cortex (MI) and in postcentral cortex (PoC) of a monkey trained to pronate and supinate its forearm. PTN responses to passive, ramp-form displacements of the forearm were examined in relation to the size of the neuron (as reflected by its antidromic latency). Larger PTNs tended to exhibit transient responses to passive limb displacement, whereas smaller PTNs more frequently showed sustained responses. These findings suggest that smaller PTNs, that make up the majority of the total PTN population, receive continuous feedback during posture as well as during the dynamic phase of movement.     

Biopsy data on the ultrastructural changes in the cerebral cortex in Vilyui encephalomyelitis

Biopsies from the cortex of the right frontal lobe of 3 patients with chronic Vilyui encephalomyelitis were examined light- and electron microscopically. The characteristic degenerative changes in the gangliocytes and especially in the nerve fibers are typical for this disease; particularly severe lesions were found in the myelin sheaths and to a lesser extent in the axons. Myelin sheaths lamella, external mitochondrial membranes and other organelles showed osmiophilic degeneration with their destruction and release of peculiar crystal-like formations having an elective localization in the processes cytoplasm and not in the perikaryon. Abnormal chromatin agglomeration, increase in size and ectopy of nucleoli were observed.     

Effect of Polidan on ultrastructural changes in the cerebral cortex and hippocampus of rats

Electron microscopy and morphometry of neurons in layer V of the somatosensory area in the neocortex and CA3 field in the dorsal hippocampus showed that single and 5-fold intraperitoneal injection of Polidan was followed by ultrastructural and metabolic changes in neurons reflecting activation of protein synthesis. The number of free ribosomes decreased; the number of polysomes and count of ribosomes in polysomes and tubules of the granular endoplasmic reticulum increased. Study of mitochondria and neuropil showed that Polidan activates synthetic processes in the neocortex and hippocampus. It should be emphasized that single treatment with Polidan led to functional activation of synthetic processes, while 5-fold injection of Polidan was followed by hyperactivation of synthetic processes and depletion of ultrastructures in the neocortex and hippocampus. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 8, pp. 221–226, August, 2006     

The synaptic organization of the prepacemaker nucleus in weakly electric knifefish, Eigenmannia: a quantitative ultrastructural study.

Summary Weakly electric knifefish (Eigenmannia sp.) produce continuous electric organ discharges at very constant frequencies. Modulations of the discharges occur during social interactions and are under control of the diencephalic prepacemaker nucleus. Abrupt frequency modulations, or chirps, which are observed predominantly during the breeding season, can be elicited by stimulation of neurons in a ventro-lateral portion of the prepacemaker nucleus, the so-called PPn-C. The PPn-C consists of approximately 100 loosely scattered large multipolar neurons which send dendrites into three territories, called dorso-medial, dorso-lateral, and Ventral. In the present ultrastructural investigation, the synaptic organization of these neurons, identified by retrograde labelling with horseradish peroxidase, was studied quantitatively.Somata and dendrites of the PPn-C receive input from two classes of chemical synapses. Class-1 boutons contain predominantly agranular, round vesicles and are believed to be excitatory. Class-2 boutons display predominantly flattened or pleiomorphic vesicles and are probably inhibitory. The action of the agranular vesicles in the synaptic boutons of these two classes may be modulated by the content of large dense-core vesicles. These comprise approximately 1% of the total vesicle population and are found predominantly in regions distant from the active zone of the synaptic bouton.The density of chemical synapses exhibits marked topographic differences. Class-1 boutons occur typically at densities of 3–12 synapses per 100 m of profile length on dendrites and cell bodies. No significant differences in density of class-1 boutons could be found between distal dendrites of the three territories, proximal dendrites and cell bodies. The density of class-2 synapses, on the other hand, increases significantly from usually less than 1 synapse per 100 m of profile length on distal dendrites to 2–3 synapses per 100 m of profile length on proximal dendrites and cell bodies.Such a topographic organization could enable the proximal elements to veto the depolarizing response of distal dendrites to excitatory inputs. The growth of dendrites in the dorso-medial territory during the breeding season, as shown in a previous study, and the concurrent doubling of excitatory input received by class-1 synapses, could overcome the inhibition caused on somata and proximal dendrites by class-2 synapses and thus account for the dramatic increase in the fish's propensity to chirp in the context of sexual maturity.     

Adrenal regeneration hypertension prevented by thyroidectomy: a quantitative ultrastructural study of the regenerating adrenal cortex.

Thyroparathyroidectomy (TPX) prevents adrenal regeneration hypertension (ARH) in female rats and concomitantly inhibits regeneration of the adrenal cortex. Removal of the thyroid gland plays the major role in preventing ARH inasmuch as parathyroidectomized adrenal-enucleated (PX-AE) rats became hypertensive, whereas thyroparathyroidectomized adrenal-enucleated rats (TPX-AE + PT) did not. Inhibition of adrenocortical regneration by TPX is reflected by a significant decrease in adrenal weight, volume of cortical parenchymal tissue per gland, and average cell volume at three weeks, compared with the regenerating adrenal gland in adrenal-enucleated thyroid-parathyroid-intact (AE) rats. Mitochondria in TPX-AE rats resembled closely those from zona fasciculata cells of a normal adrenal gland; stereologic techniques for electron microscopic examination confirmed that mitochondrial volume/cell and surface area of total mitochondrial membranes/cell (outer/inner membranes plus cristae) of adrenocortical cells from TPX-AE rats did not differ significantly from those of AE animals. The surface area of mitochondrial cristae of TPX-AE rats, however, was significantly greater than that of AE rats, whereas the surface area of the inner/outer mitochondrial membrane of the TPX-AE group was decreased significantly as compared with that of the AE group. The diameter of mitochondria in TPX-AE rats was larger than in the AE group, although the number of mitochondria/cell was significantly less in TPX-AE rats than in AE rats. Although TPX had no significant effect on the levels of DOC or corticosterone in the serum of quiescent AE rats as compared with TPX-AE rats, the rise in DOC in the serum after ether stress was blunted in the TPX-AE group as compared with that in the AE group. The rise in corticosterone in the TPX-AE group was comparable to that of the AE animals. Thus, partial inhibition of adrenal regeneration in TPX-AE rats in combination with a blunted rise in DOC levels in response to stress may well contribute to the prevention of ARH.     

人巨细胞病毒感染胎鼠大脑皮质神经元显微和超微结构观察

目的：研究人巨细胞病毒（HCMV）经小鼠胎盘垂直传播致胎鼠大脑皮质神经元病理改变的显微和超微结构特征。方法：在8－12周龄Balb/c雌雄小鼠腹腔内接种HCMV后,交配,特孕鼠临产时剖腹取出10份胎鼠双侧大脑皮质,用光镜和透射电射观察了神经元的显微和超微结构,同时进行了病毒分离。结果：光镜下可见胎脑微血管扩张充血,神经元数目明显减少,残存的神经元缺血性改变,间质水肿;可见到软化灶及受染神经元核内及胞质内HCMV特征性哮碱性和哮酸性包涵体,电镜下可见受染神经元核仁消失,胞质内线粒体,内质网和高尔基复合体等重要细胞器结构严重破坏呈空泡状或溶解;并找到人类疱疹病毒样颗粒。病毒分离阳性,在同时设置的正常对照组则无上述阳性发现。结论：HCMV能通过小鼠胎盘感染子代胎鼠大脑皮质神经元,并导致神经元结构破坏死亡。     

The cholinergic innervation develops early and rapidly in the rat cerebral cortex: a quantitative immunocytochemical study.

A recently developed method for determining the length of cholinergic axons and number of cholinergic axon varicosities (terminals) in brain sections immunostained for choline acetyltransferase was used to estimate the areal and laminar densities of the cholinergic innervation in rat frontal (motor), parietal (somatosensory) and occipital (visual) cortex at different postnatal ages. This cortical innervation showed an early beginning, a few immunostained fibers being already present in the cortical subplate at birth. In the first two postnatal weeks, it developed rapidly along three parameters: a progressive increase in the number of varicosities per unit length of axon, and a lengthening and branching of the axons. Between postnatal days 4 and 16, the number of varicosities increased steadily from two to four per 10 microm of cholinergic axon. The mean densities of cholinergic axons increased from 1.4 to 9.6, 1.7 to 9.3 and 0.7 to 7.2 m/mm(3), and the corresponding densities of varicosities from 0.4 to 3.9, 0.4 to 3.5, and 0.2 to 2.6x10(6)/mm(3) in the frontal, parietal and occipital areas, respectively. The rate of growth was maximal during these first two weeks, after which the laminar pattern characteristic of each area appeared to be established. Adult values were almost reached by postnatal day 16 in the parietal cortex, but maturation proceeded further in the frontal and particularly in the occipital cortex.These quantitative data on the ingrowth and maturation of the cholinergic innervation in postnatal rat cerebral cortex substantiate a role for acetylcholine in the development of this brain region and emphasize the striking growth capacity of individual cholinergic neurons.     

Zona reticularis in aging spontaneously hypertensive rats: a quantitative ultrastructural study of 70- and 95-week-old animals.

The zona reticularis of 70- and 95-week-old female Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats was studied by quantitative stereologic techniques. The zona reticularis in the adrenal gland of 70-week-old SH rats was virtually identical to that of 70-week-old WKY rats. In both SH and WKY rats at 95 weeks of age, however, there was hypertrophy of smooth endoplasmic reticulum reflected quantitatively in increased volume and surface area, as compared with that of WKY rats or SH rats at 70 weeks of age. Ninety-five-week-old WKY rats had a significantly greater mitochondrial volume/cell and surface area of mitochondrial membranes than SH rats. Inclusion of lipid droplets within mitochondria was seen in zona reticularis cells from SH and WKY rats at 70 weeks of age; mitochondria-lipid-droplet association was more frequent at 95 weeks of age. The volume of lipofuscin per cell was significantly greater in WKY than in SH rats at 95 weeks of age. Thus, by quantitative techniques, one can see that the zona reticularis of 95-week-old SH rats differs from that of WKY rats, principally in the presence of smaller cells with a smaller surface area of mitochondrial cristae and a reduced volume of mitochondria, lipofuscin, and lipid droplets.     

The adrenal cortex in spontaneously hypertensive rats. A quantitative ultrastructural study.

The adrenal cortex of spontaneously hypertensive rats (SHR) has been examined by quantitative morphologic techniques for electron microscopy. The volume and surface area of smooth endoplasmic reticulum and the volume of Golgi apparatuses in zona glomerulosa cells of SHR was significantly greater than those of Wistar-Kyoto strain (W/KY) normotensive controls; the volume of lipid droplets and nucleus was significantly less in SHR than in W/KY animals. A stimulation of the zona glomerulosa in SHR may well be attributable to the elevation in systolic blood pressure. A distinct lipid-free subglomerulosa was observed in the adrenal gland of W/KY rats; the cell volume was similar to that of the zona glomerulosa although the cells showed a significantly greater volume of mitochondria and surface area of mitochondrial membranes and greater volume of smooth endoplasmic reticulum and lysosomes. In the zona fasciculata, cell volume, volumes and surface area of mitochondria and smooth endoplasmic reticulum, and volume of lipid droplets were significantly lower in SHR than in W/KY rats. The volume of the Golgi apparatus was greater in SHR than in W/KY rats. Glycogen particles were observed in focal areas of some zona fasciculata cells. The adrenal cortex of another strain of normotensive Wistar rat (W/CFN) was compared with that of the W/KY and SHR. Although the relative adrenal weights of SHR and W/KY animals were identical, the weight of that in W/CFN was significantly smaller. The volume of the zona glomerulosa of SHR was significantly greater than that of W/KY although the volume of the zona glomerulosa in W/CFN was significantly greater than the other two groups. The volume of nucleus and lipid droplets of zona glomerulosa in W/KY was significantly greater than that in the S/CFN; the volume of the cell, mitochondria, smooth endoplasmic reticulum, lipid droplets, and lysosomes, and the surface area of smooth endoplasmic reticulum and mitochondrial membranes of W/KY animals was significantly greater than those of W/CFN animals. It is concluded that the W/CFN rat is not an appropriate control for spontaneously hypertensive rats.     

Morphological changes in the cerebral cortex after a stroke

29 brains of right-handed persons who died within the period of 4 hours to 6 years after the stroke were studies. The patients had various disorders of speech and movements, partial or complete speech recovery was observed in 10 cases. Aphasias resulted from the lesions of associative fibers connecting the speech zones of the brain cortex, direct destruction of speech regions, in cases of hematoma pressure on cortex speech areas. Changes in neurons, nerve fibres and neuroglia in the cortex of speech areas were determined by the time passed after the stroke. They were also dependent on the site and size of the focus and, to a certain extent, correlated with a clinical picture. The changes also depended on localization and the size of lesion. Sometimes the changes correlated with clinical data. Clinical and morphological comparisons indicate that a correlation exists between speech recovery degree and the intensity of repairing processes in neurons and nerve fibres in cortical speech areas.     

Neuronal and synaptic organization of the centromedian nucleus of the monkey thalamus: a quantitative ultrastructural study, with tract tracing and immunohistochemical observations

Summary The ultrastructure of the centromedian nucleus of the monkey thalamus was analysed qualitatively and quantitatively and projection neurons, local circuit neurons, and synaptic bouton populations identified. Projection neurons were mostly medium-sized, with oval-fusiform or polygonal perikarya, few primary dendrites, and frequent somatic spines; local circuit neurons were smaller. Four basic types of synaptic boutons were distinguished: (1) Small- to medium-sized boutons containing round vesicles (SR) and forming asymmetric contacts, identified as corticothalamic terminals. (2) Heterogeneous medium-sized boutons with asymmetric contacts and round vesicles, similar to the so-called large round (LR) boutons, which were in part of cortical origin. (3) Heterogeneous GAD-positive small- to medium-sized boutons, containing pleomorphic vesicles and forming symmetric contacts (F1 type), which included pallidothalamic terminals. (4) Presynaptic profiles represented by GAD-positive vesicle-containing dendrites of local circuit neurons. Complex synaptic arrangements, serial synapses and triads with LR and SR boutons engaging all parts of projection neuron dendrites and somata, were seen consistently, whereas classical glomeruli were infrequent. LR and SR boutons also established synapses on dendrites of local circuit neurons. F1 boutons established synapses on projection neuron somata, dendrites and initial axon segments. Compared to other previously studied motor-related thalamic nuclei, differences in synaptic coverage between proximal and distal projection neuron dendrites were less pronounced, and the density of synapses formed by local circuit dendrites on projection neuron dendrites was lower. Thus, compared to other thalamic nuclei, the overlap of different inputs was higher on monkey centromedian cells, and centromedian inhibitory circuits displayed a different organization.     

Experimental rabies: ultrastructural quantitative analysis of the changes in the sciatic nerve

To study the pathology of peripheral nerves in experimental rabies infection, street rabies virus ws inoculated into the right footpad of two groups of mice, A and B, which received, respectively, 10(4.5) LD50 and 10(3.5) LD50 of the virus. Paralysis was observed in 60% of animals of group A and 20% of group B. The main ultrastructural abnormality present in the sciatic nerves was degeneration of about 40% of myelinated axons. Only occasional unmyelinated axons were degenerated. Figures were similar for nerves of either side and for both groups. Frequency histograms of axonal diameter showed axons of all sizes to be altered in group A, whereas in group B there was tendency for larger axons to be damaged. Electron microscopy showed no typical bullet-shaped viral particles. Asymptomatic animals which received the higher dose of the inoculum showed a small (less than 1%) percentage of necrotic myelinated axons.     

Loss of dendritic spines in aging cerebral cortex

Summary Previous work has shown that the dendritic spines of pyramidal neurons of the cerebral cortex are sensitive to a wide variety of environmental and surgical manipulations. The present study shows that the normal aging process also affects these spines. The spines were studied with the light microscope in Golgi preparations from rats ranging in age from 3 to 29.5 months. Visible spines were counted on either 25 or 50 segments of the basal dendrites, apical dendrites, oblique branches, and terminal tufts of layer V pyramidal cells in area 17. A progressive loss of spines occurred at each of these loci. The smallest observed spine loss (24%) occurred on the dendrites of the terminal tuft, and the largest (40%) on the oblique branches. Age-related spine loss appears to affect all animals, and for animals of any one age the overall loss is similar. However, the cell-to-cell variability within an individual animal is pronounced, some cells with high spine densities being present at every age examined. As a general rule, there is a positive relationship between visible spine density along the apical dendrite as it traverses layer IV and the thickness of the dendrite. With advancing age, the relatively thick dendrites decrease in number so that the thinner dendrites make up an increasingly larger proportion of the total apical dendrite population. Questions that remain for the future include the genesis of the spine loss, its relation to other aging changes, and its functional significance for the neuron.Supported by United States Public Health Service Program Project Grant HDO-5796-03 and Research Grant NB-07016     

An ultrastructural study of methionine sulphoximine-induced glycogen accumulation in astrocytes of the mouse cerebral cortex.

Glycogen distribution in the mouse cerebral cortex was examined with electron microscopy following treatment with the experimental convulsant, methionine sulphoximine (M.S.O.). Both at 24 and 48 h followed administration of M.S.O., accumulation of particulate glycogen was prominent in astrocytes throughout the cerebral cortex. In astrocyte cell bodies and in subpial, pericapillary and perineuronal astrocyte processes the glycogen often completely filled the cytoplasm, crowding the remaining organelles and inclusions. The present findings correlate well with biochemical studies of M.S.O. effects of glutamine synthetase activity and energy metabolism. It is suggested that the glycogen may be derived from glutamate which under normal conditions would be converted to glutamine.     

Quantification of gray matter changes in the cerebral cortex after isolated cerebellar damage: a voxel-based morphometry study

There is growing evidence based on behavioral and functional imaging studies about the cerebellar involvement in the modulation of cognitive functions. However, it still remains to be clarified how the cerebellum interacts with brain regions sub-serving different cognitive domains. In this study we used magnetic resonance imaging (MRI) and voxel based morphometry (VBM) to investigate changes of cerebral gray matter (GM) density in 15 patients with a focal cerebellar damage (CD) compared to 15 healthy controls. T2-weighted scans and T1-weighted volumes were collected from each subject. With the exception of the cerebellar lesion, none of the patients showed any additional brain MRI abnormality. T1-volumes were analyzed by voxel-based morphometry. Consistent with their neuropsychological abnormalities, patients with right-CD compared to controls showed a reduction of GM density mainly involving the left frontal, parietal and temporal lobes. Conversely, patients with left-CD did not show any significant neuropsychological or cerebral GM abnormality. The present study indicates that specific GM changes may be detected in patients with isolated CD and cognitive dysfunction. We discuss the findings in terms of cerebellar influence on the neuronal networks involved in higher level functions of the association cortex.     

Early histogenesis in the mouse cerebral cortex: a Golgi study

The early histogenesis in the cerebral cortex of the mouse was studied with a modification of the rapid Golgi method. Three stages can be distinguished first, a period during which the telencephalon is exclusively populated with neuroepithelial cells (till E12); secondly the transient stage of the primordial cortical organization, characterized by the presence, in the outer part of the neural tube, of a loose network of primitive horizontal nerve cells and third, the appearance of the early cortical plate (E14) which contains closely packed, radial bipolar nerve cells. In addition to some salient morphological features of the various cell types, the technique also reveals the importance of efferent fibers from the cortex during the early cortical development.     

Peritubular capillaries in chronic renal allograft rejection: a quantitative ultrastructural study

Peritubular capillaries (PCs) with a circumferentially multilayered basement membrane have been suggested as an ultrastructural indicator of chronic renal allograft rejection (CR). The authors validated this lesion as a marker for CR, by analyzing its quantitative features, specificity, and sensitivity in 169 renal biopsy specimens. The mean number of circumferential layers (PCcirc) and the incidences of the grades (mild: 2 to 4, moderate: 5 to 6, severe: 7 or more layers) were investigated in biopsy specimens involving CR (CR(Bx), n = 46), acute rejection (n = 11), normal kidneys (n = 20), psoriatics treated with cyclosporine (n = 13), renal transplants with chronic cyclosporine toxicity (n = 12), native kidney diseases (NKD, n = 56), and transplant nephrectomies attributable to CR (Cr(nephr), n = 11). CR was diagnosed with regard to the clinical features and the presence of intimal fibrosis in 41 biopsy specimens or transplant glomerulopathy in 35 biopsy specimens (cg; identified only by electron microscopy in 10 cases). NKD included chronic glomerulonephritis, chronic tubulointerstitial nephritis, benign nephrosclerosis, thrombotic microangiopathy, diabetic nephropathy, and renal disease in elderly patients (median age, 72 years). All PCs around glomeruli were sampled (median, 14 profiles per case). PCs with a moderate/ severe lesion appeared as serrated profiles with a thick, ribbon-like basement membrane layer in semithin plastic sections. The numbers of circumferentially multilayered PCs were significantly characteristic of CR (PCcirc in CR(Bx): 2.87+/-1.83 SD; range, 0 to 7.36; P < .001 v other groups). A severe lesion occurred exclusively in CR (in 12% of the PCs in CR(Bx), and in 38% in CRnephr). A moderate lesion was observed in 0.6% of the PCs in NKD, 16% in CR(Bx), and 21% in CRnephr. Three or more PCs with a moderate lesion were encountered only in CR. A mild lesion was not suggestive of CR at all. In CR(Bx), 27 cases showed a severe lesion or 3 or more PCs with a moderate lesion (cpc; sensitivity: 59%). Four of the 27 cases lacked cg. The cumulative incidence of cpc and cg was 85%. In transplants with cyclosporine toxicity, the presence of cpc verified the coexistence of CR in 7 specimens. In conclusion, cpc is a specific marker of CR. The incidence of cpc increases as CR progresses. The lesion may be caused by a low-grade rejection injury to the PCs. Careful analysis of semithin sections promotes the better sampling of cpc. An ultrastructural demonstration of cpc and cg defines CR more precisely than does light microscopic evaluation per se.     

Death of memory T-cell subsets in humans: changes during aging

Aging is characterized by a progressive decline in various T-cell functions that are associated with a deficiency of naive and central memory T-cell subsets and the accumulation of oligoclonal effector memory T-cell subsets. In this article, we briefly review different pathways of death signaling and alterations in apoptotic signaling pathways in order to understand changes in various T cells in human aging.