Alterations of both responder T cells and stimulator non-T cells are responsible for abnormal mixed lymphocyte reaction in aged humans

Summary The autologous and allogeneic mixed lymphocyte reactions of 15 young and 15 aged human adults were compared. Both autologous and allogeneic mixed lymphocyte reactions were significantly reduced in the aged group. T cells from aged adults displayed a reduced proliferative response to non-T cells of either aged or young adults. T cells from young adults also showed a reduced proliferative response to non-T cells from aged adults. Sera from aged adults, showing depression of autologous and allogeneic mixed lymphocyte reaction, did not exert any inhibitory effect on the autologous and allogeneic mixed reaction of lymphocytes from young donors. These data suggest that depression of mixed lymphocyte reaction in aged humans probably reflects intrinsic abnormalities of both responder T cells and stimulatory non-T cells. This work was supported by a grant from theConsiglio Nazionale delle Ricerche (CNR), Roma, Italy ‘Progetto Finalizzato Medicina Preventiva, Sottoprogetto Meccanissmi di Invecchiamento’.     

Association between memory impairment and insomnia among older adults

Chronic insomnia and memory impairment are both common complaints among older adults. Even so, only a few studies to date have examined the effects of chronic insomnia on memory processes among older people, and the results of these studies are contradictory. Therefore, in the current study we examined whether late-life insomnia is associated with the memory status of older adults. The study population comprised two groups: 50 older adult subjects without sleep disorders, and 23 older adult insomniacs. Memory processing for each of the two groups was evaluated using the Rey Auditory Verbal Learning Test (AVLT). The results demonstrate that chronic insomnia in older adults is associated with impairment in memory. Specifically, we found that older people suffering from late-life insomnia exhibit significantly reduced performance in learning rate and in temporal order judgment as well as significantly reduced resistance to proactive interference. The present findings suggest that late-life insomnia may be one of the factors contributing to the decline in memory processing seen among older people.     

Autophagy,its mechanisms and regulation: Implications in neurodegenerative diseases

Autophagy is a major regulatory cellular mechanism which gives the cell an ability to cope with some of the destructive events that normally occur within a metabolically living cell. This is done by maintaining the cellular homeostasis, clearance of damaged organelles and proteins and recycling necessary molecules like amino acids and fatty acids. There is a wide array of factors that influence autophagy in the state of health and disease. Disruption of these mechanisms may not only give rise to several autophagy-related disease, but also it can occur as the result of intracellular changes induced during disease pathogenesis causing exacerbation of the disease. Our knowledge is increasing regarding the role of autophagy and its mechanisms in the pathogenesis of various neurodegenerative diseases such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and Amyotrophic lateral sclerosis. Indeed, getting to know about the pathways of autophagy and its regulation can provide the basis for designing therapeutic interventions. In the present paper, we review the pathways of autophagy, its regulation and the possible autophagy-targeting interventions for the treatment of neurodegenerative disorders.     

Sarcolemmal K(ATP) channels in ageing

This review highlights some recent research addressing sarcolemmal K(ATP) channels in ageing. These channels are abundant in cardiac myocytes where they are essential in coupling the cellular metabolic state with membrane excitability. The opening of sarcolemmal ATP-sensitive K+ (K(ATP)) channels occurs during ischaemia and protect the heart against injury. Age-dependent changes in the myocardial susceptibility to ischemia have been observed in different species, including humans. Recent research has demonstrated that ageing is associated with decrease in numbers of sarcolemmal K(ATP) in hearts from females, but not males. This phenomenon seems to be associated with age-dependent decrease in concentration of circulating estrogens. In the heart, SUR2A, a regulatory subunit of K(ATP) channels, is present in excess over Kir6.2, a pore-forming K(ATP) channel subunit. The consequence of this is that SUR2A is a subunit that controls the number of sarcolemmal K(ATP) channels. Estrogens specifically up-regulate SUR2A and, thereby, control the number of sarcolemmal K(ATP) channels. Age-dependent loss of sarcolemmal K(ATP) channels creates a cardiac phenotype more sensitive to ischaemia, which may explain, at least in part, an ageing-associated decrease of myocardial tolerance to stress that occurs in elderly women.     

Age and binding within-dimension features in visual short-term memory

Older adults have difficulties in binding information in long-term memory (e.g. objects with colours). The effect of age on visual short-term memory (VSTM) binding is less well understood. Recent evidence has suggested that older adults' VSTM for colours bound to shapes or for locations bound in configural representations may be preserved. In two experiments we investigated whether this lack of an age effect on VSTM for bound features can be reproduced when features are drawn from the same dimension (i.e. colour-colour binding) and when spatial clues are not available. Younger and older adults were presented with two sequential arrays of unicoloured or bicoloured objects and their accuracy in detecting changes between arrays was used as the measure of memory performance. Memory was assessed using a change detection paradigm for unicoloured objects and for bicoloured objects with changes in colour conjunctions (i.e. colours swapping between objects) or with changes in non-conjunctive colours (i.e. colours replacing colours in the study array). Both young and older adults were less accurate at remembering objects defined by colour conjunctions than unicoloured objects or objects composed of two non-conjunctive colours (Experiment 1). Increasing task demands in terms of memory and perceptual load had no greater effect on the older than the younger adults (Experiment 2). We suggest (1) that colours were not integrated into single units in VSTM; (2) that remembering the binding between colours has a cost; and (3) that neither of these effects are age-dependent.     

Responses of old men to repeated bouts of eccentric exercise of the elbow flexors in comparison with young men

A bout of eccentric exercise confers protection against subsequent bouts of the same exercise. This study investigated whether the protective effect would be produced similarly between old and young adults. Eight old men (70.5 ± 4.1 years) and ten young men (20.4 ± 2.0 years) performed two bouts of eccentric exercise of the elbow flexors (six sets of five eccentric actions) separated by 4 weeks. Changes in maximal isometric strength, range of motion (ROM), upper arm circumference (CIR), plasma creatine kinase (CK) activity, myoglobin (Mb) concentration, and muscle soreness (SOR) before, immediately after, and 1, 24, 48, 72 and 96 h following exercise were compared between bouts, and between groups by a two-way repeated measures ANOVA. Changes in the measures following the first bout were significantly (P < 0.05) smaller for the old than the young group. The young group showed significantly (P < 0.05) smaller changes in all measures following the second bout than the first bout; however, the old group had the protective effect only for ROM, Mb, and SOR. The magnitude of the effect observed for ROM and Mb concentration in the old group was significantly (P < 0.05) smaller compared with that of the young group. These results suggest that the protective effect conferred by the first bout was less for the old than the young group. This may be due to the less muscle damage after the first bout in the old subjects, but it is also possible that the protective effect of old adults does not last as long as that of young adults.     

Decreased density of beta-adrenergic and muscarinic cholinergic receptor sites in the vasa nervorum of aged rats

The pharmacological profile and the anatomical localization of beta-adrenergic and muscarinic cholinergic receptors of the vasa nervorum were studied in sections of sciatic nerve using radioreceptor binding and light microscope autoradiography techniques. Sprague—Dawley rats of 4 and 24 months of age were used. [³H]Dihydroalprenolol (DHA) and [³H]quinuclidinyl benzilate (QNB) were used to label beta-adrenergic and muscarinic cholinergic receptors, respectively. The ligands were bound to sections of rat sciatic nerve in a manner consistent with the labelling of beta-adrenergic or muscarinic cholinergic receptors in the 2 age groups investigated. The dissociation constant (K_d) values (about 1.37 nM for [³H]DHA and 0.75 nM for [³H]QNB) did not significantly change between 4- and 24-month-old rats. The maximum concentration of binding sites (B_max) for [³H]DHA was decreased by about 35% in 24 in comparison with 4-month-old rats. The B_max value autoradiogaphy revealed the development of specific silver grains in the medial layer of epineurial and perineurial arteries in sections of sciatic nerve exposed either to [³H]DHA or [³H]QNB. The number of silver grains developed in epineurial and perineurial arteries of rats of 24 months is significantly lower than in animals of 4 months. The above results suggest the occurrence of an age-dependent loss in the density of beta-adrenergic and muscarinic cholinergic receptors of vasa nervorum.