Mechanisms of ageing and development
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Comparative Study
Comparison between the effects of aging and hyperoxia on glutathione redox state and protein mixed disulfides in Drosophila melanogaster.
The main purpose of this study was to determine whether experimental enhancement of oxidative stress by exposure to hyperoxia is an appropriate model for the acceleration of the normal aging process or for establishing a causal association between oxidative stress and aging. Insect tissues are directly exposed to ambient air via the tracheolar invaginations and are thus highly susceptible to oxidative stress under hyperoxic conditions. Amounts of glutathione (GSH), glutathione disulfide (GSSG) and protein mixed disulfides (PrSSG) were compared under normoxic and 100% ambient oxygen in males of two different strains of Drosophila melanogaster (Oregon R (WT) and y w strains). ⋯ Under hyperoxia, y w flies did not exhibit an increase in GSSG amount or a decline in GSH:GSSG ratio, whereas WT flies showed a decline in GSH:GSSG ratio only during the later part of hyperoxic exposure. In neither strain there was a progressive increase in PrSSG amount under hyperoxia. Results indicate that hyperoxia (100% oxygen) neither reproduces nor accelerates the pattern of alterations in glutathione redox state and PrSSG content observed during aging under normoxic conditions, although some other indicators of oxidative stress may be affected.
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Memory T cells can be classified as central memory (T(CM), CD45RA(neg)CCR7(+)), effector memory (T(EM), CD45RA(neg)CCR7(neg)), and terminally differentiated cells (T(TD), CD45RA(+)CCR7(neg)) with different homing and effector capacities. In 101 healthy subjects aged from 5 to 96 years, distinct dynamics were evidenced between circulating CD4(+) and CD8(+) T cell populations. Naive CD4(+) and CD8(+) T cells decreased linearly with age, CD8(+) twice more rapidly. ⋯ Almost all CD8(+) T(TD) and some CD8(+) T(EM) had lost CD28 expression. Despite different dynamics, each individual CD4(+) naive and memory subset was correlated to the synonymous CD8(+) subset. Half of the subjects aged 65 years or older were characterized by extremely reduced CD8(+) naive and increased CD8(+) T(TD) cell counts, which could indicate an acceleration of the decay of the immune system from this age onward.
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Pneumococcal pneumonia is a significant health concern for pediatric, healthy adult, and elderly populations. The newly licensed pneumococcal 7-valent conjugate (diphtheria CRM197 protein) vaccine, Prevnar, and a second generation experimental 9-valent product have demonstrated, for the first time, a clear and significant impact on pneumococcal pneumonia in children. The potential for saccharide-conjugate vaccines to help prevent pneumococcal pneumonia in adult and elderly populations and potential barriers to the introduction of a conjugate vaccine in adults are discussed.
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Aging is accompanied by an altered stress response that underlies increased susceptibility of the elderly patients to physiological stress such as infection and sepsis. In the present study, we investigated the effects of aging on mortality, hypothermia, and cytokine induction in mouse models of intra-abdominal sepsis and endotoxemia. Systemic inflammation associated with either cecal ligation/puncture (CLP) or injection with bacterial endotoxin, lipopolysaccharide (LPS), resulted in a significantly elevated mortality rate in aged (24 months) compared to young (4 months) mice. ⋯ The serum level of IL-6 showed a strong correlation with degrees of hypothermia. In the heart and lungs, the induction of mRNA for IL-6 and IL-10 was also significantly enhanced with aging. These results clearly demonstrate an age-associated increase in mortality, hypothermia, and induction of IL-6 during endotoxemia and sepsis.
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Thymic atrophy or thymus absence causes depressed thyroid-thymus axis (TTA) efficiency in old, young propyl-thiouracil (PTU) (experimental hypothyroidism) and in young-adult thymectomised (Tx) mice, respectively. Altered zinc turnover may be also involved in depressed TTA efficiency. Zinc turnover is under the control of zinc-bound metallothioneins (Zn-MTs) synthesis. ⋯ Thymus from old zinc-treated mice induces the same restoring effect when transplanted in Tx recipients. However, Tx mice display natural normalisation in MTmRNA and in nutritional-endocrine-immune profile in the long run. Therefore, Zn-MTs (I+II) are crucial in zinc homeostasis for endocrine-immune efficiency during the entire life assuming a role of potential and novel 'biological clock of ageing'.