Age-related morphological changes in lymphocytes as a model of aging.

The same age-related morphological changes have been observed in the lymph node and spleen lymphocytes of old untreated Wistar rats and CBA/Ca mice. The same age-related changes were also observed in the peripheral lymphocytes of healthy humans. The most important changes were seen in the mitochondria of the lymphoid cells. They were sometimes swollen; the mitochondrial cristae disappeared and were replaced by myelin-like forms or filamentous structures. The mitochondrial changes developed only in non-labelled lymphoid cells, presumably the T cells. It is suggested that lymphocytes be used as a morphological model for the study of aging and its modification.

Effect of 2-mercaptoethanol on some metabolic indices of ageing of CBA/Ca inbred mice.

It has been shown in several studies that 2-mercaptoethanol (2-ME) improves the life span and aspects of life performance of laboratory animals. To obtain further details on the beneficial effects of 2-ME, a long-term study has been performed on male CBA/Ca inbred mice treated with this antioxidant. Four month-old mice were each given 4 micrograms of 2-ME in physiological saline via intraperitoneal (i.p.) injection 3 x per week. Measurements were made of the following: cold tolerance (heat performance), apparent total body protein turnover (T1/2), changes in the major lipid and fatty acid compositions of the liver, superoxide dismutase activity and formation of malondialdehyde and observations on a range of pathological changes. It was found that the basal rectal temperatures of the treated mice were higher and in the oldest group, heat performance capacity was better than those of the controls. After about 1 year of age the apparent biological half-life time of total body protein (T1/2) was observed to be shorter in the treated mice. Significant increases were observed to occur in the proportions of the polyunsaturated fatty acids in the lipids of the liver in the mice injected with 2-ME. Although no differences were observed in the superoxide dismutase activities, malondialdehyde concentrations in the livers of the experimental mice were significantly increased. Autopsy data showed that Dunn-sarcomas associated with amyloidoses occurred more frequently in the untreated mice.

Long-term observations on the effect of polyadenylic acid in mice of different ages.

In order to better life performance, polyadenylic acid (poly (A) ) was given intraperitoneally to CBA/Ca mice for almost a two-year period. This substance, as one of the components of double-stranded polynucleotides (like poly A:U), is known to improve some immune responses of the aging organism. Five approaches (changes in body-weight, adaptation to cold stress, biological half-life of body proteins, mortality and pathology) were applied to test the effects of this substance on life performance. It was found that the beneficial effects of double-stranded polynucleotides cannot be mimicked by polyadenylic acid only, despite its anti-senescence effect, namely, it accelerates the apparent protein turnover, cf., biological half-life. Polyadenylic acid shortens life-expectancy (because of the higher mortality rate of mice). Possible mechanisms of these actions are discussed.

Effect of aging on cold tolerance and thyroid activity in CBA/Ca inbred mice.

Relationships between cold tolerance, serum levels of thyroxine (T4), thyronine (T3), and thyrotropine (TSH), and thyroid morphometry have been investigated in male CBA/Ca inbred mice at various ages through their life span. From the data obtained it appeared that there was an age-related decrease in cold tolerance up to 18 months of age which was followed by an increase, the age effect being most apparent in relation to cold resistance and cold tolerance during the recovery period following cold exposure. The age-related changes in cold tolerance appeared to be associated with changes in the serum concentrations of T3, T4, and TSH. In contrast to the T3 serum levels which showed a decrease at 36 months, the thyroxine contents showed a perceptible decrease from the age of 12-18 months onwards. A similar pattern was observed for the TSH levels, with a peak at 21 months, followed by a decline at 30 months. A relationship with age between serum T4 level and thyroid weight was indicated together with structural changes in the thyroid gland, particularly during senescence, for example the size and number of thyroid epithelial cells had become enlarged by 30 months of age.

Herpesnephropathy.

Two cases of acute renal insufficiency occurred in association with episodes of severe encephalitis due to herpes simplex type I. The possibility was considered that the renal failure was due to viral infection of the kidneys, and animal experiments were carried out in an attempt to confirm this. Young New Zealand albino rabbits were infected i. v. with HSV type I; the virus antigen was detected in the kidney of 8 of 10 animals, and IgG was found on the GBM in 9 of 19 animals. Viruria was observed in 12 of the 29 infected animals, and electronmicroscopic examination confirmed the presence of immune complexes in the glomeruli.

Physiological age-related changes: cross-sectional and longitudinal studies.

Physiological age-related changes were investigated by cross-sectional and longitudinal studies. The data of the study were derived from volunteers admitted to the Gerontology Center in Budapest. In the follow-up study 864 subjects took part, and in the cross-sectional study 2,281 individuals. The 20-year longitudinal study and the cross-sectional examination showed that from a clinical standpoint the most important observation is that several biochemical data do not change with age. No changes were found in the values in erythrocyte sedimentation, hemoglobin, hematocrit, serum total protein, albumin, liver function, glucose, creatinine, triglyceride, and HDL-cholesterol levels. Changes were observed in the levels of HDL-cholesterol, immunoglobulins, rheumatoid factors, antinuclear factors, morphology of lymphocytes, serum TSH and T3 concentration, and systolic blood pressures.

Lipofuscin in lymphocytes and plasma cells in aging.

The age-related changes in spleen and lymph node lymphocytes and plasma cells of Wistar rats and in the peripheral lymphocytes of healthy human individuals were examined. Similar changes were described in human and rat lymphocytes and plasma cells consisting of mitochondrial lesions. The cristae of the mitochondria disappeared and were replaced by myelin-like structure, lamellar structure, electron-dense and electron-translucent material. It is supposed that this material corresponds to lipofuscin.

Lymphocyte subpopulation changes by aging.

Peripheral blood lymphocyte suspensions of healthy young and aged subjects were tested for the percentage of (1) E-rosetting cells by three different modifications of the rosette technique; (2) alpha-naphthylacetate esterase positive cells of different staining patterns; (3) IgG-Fc receptor positive cells; (4) C3 receptor positive cells; (5) labile and stable bound surface immunoglobulin positive cells; and (6) cells bearing different classes of immunoglobulins on their surface or intracytoplasmically. Age dependent changes were registered both within the T-cell and the B-cell subpopulations, some of which may be due to in vivo activation of lymphocytes. Attention is called to some technical aspects of lymphocyte subpopulation determinations and to the significance of quantitative changes in the proportions of lymphocyte subpopulations in respect to the age dependent functional changes of lymphocytes.

Autoimmunity and normal immune functions in aged humans.

The high frequency of ANA, A-LDL and RF in advanced age suggests that AABs are present in the majority of aged subjects. CIC incidence determined by three methods is far below AAB incidence; only the Clq solubility test suggests an increased CIC incidence in aged as compared to young subjects. Simultaneous occurrence of AABs of different specificities or CIC determined by two or three methods is rare and both AAB and CIC levels are usually low. AAB prevalence in CIC-positive individuals seems to depend on the specificity of the AAB. CIC positivity is associated with relatively low Clq concentrations; however, usually not with Clq concentrations below the normal range. Neither ANA nor CIC positivity seems to correlate with DNA synthetic response to PHA, but ANA positivity may be associated with low responses to allogeneic cells. ANA positivity and, to a lesser extent, CIC positivity seems to be connected with enhanced killer cell activity. The concept of some AABs and CIC as autoregulatory factors of the humoral immune system compensating for the thymus-dependent regulation in old age is stressed.

The incidence of immunoglobulin-A deposits in glomerular diseases and its morphological examination: nephropathy with mesangial IgA dense deposits.

The presence of IgA with IgG, C', IgM and fibrin in 365 renal biopsy specimens has been studied by the immunohistological method. Glomerular IgA deposits were found in 38 cases (10.4%). The patients were divided into two groups according to the localization of IgA: 13 cases (3.56%) belonged to the first group, in which IgA showed diffuse mesangial localization. Light microscopic examination showed various stages of proliferative glomerulonephritis. These cases corresponded to the nephropathy described by Berger. In 25 cases (6.85%), belonging to the second group, the glomerular localization of IgA was found to be segmental and peripheral, appeared always in patches and was present with various histological alterations. Differentiation of the two kinds of alteration is possible primarily on the basis of the immunohistological pattern, but light microscopic and electron microscopic examination might also be helpful.