Aging (Milan, Italy)最新文献

In a first experiment, the conditioned suppression of the proboscis extension response (PER) to sucrose was measured in young, middle-aged and old male Drosophila melanogaster flies living at either 1, 3 or 5 g. Flies were starved and then subjected to a learning task involving a sucrose stimulus, followed by an aversive one applied to their forelegs. In this learning task, flies learn to not extend their proboscis when walking on sucrose. Flies which have lived in hypergravity (HG) had a lower number of PER suppressions than 1 g ones, and this finding was mainly due to young and middle-aged flies. In a second experiment, the habituation of the PER was studied using as stimulation sucrose solutions 2-fold (first experiment), 4-fold (second one) or 8-fold (third one) higher than the individual sucrose threshold. Middle-aged and old flies habituated more slowly than young flies in the second and third experiments. In the third experiment, a decreasing speed of habituation was observed when gravity increased; this result was mainly due to young flies, and no gravity effect was observed in the other two age groups. This whole set of results suggests that HG-kept flies do not age faster than 1 g ones, as far as these learning and habituation tasks are concerned. It seems possible that HG acts like a mild stress to which flies adapt; if applied for a long time, HG could induce a premature aging, as observed in the previous papers of this series.

Laxatives are frequently taken especially by older persons, who have multiple diseases and are disabled. Major differences exist among countries in the type of laxatives taken, and knowledge of the intake patterns is important because of the potential adverse effects associated with particular ingredients. Laxatives and factors related to their use are described in a sample of 3257 patients admitted to 58 hospitals of the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) in 1991. The mean age was 68.2 years, median 73 years, more than 30% were age > or = 80 years, and 48.7% were men. The overall prevalence rates of laxative use during hospital stay and prior to admission were 11.5% and 11.3%, respectively. Increasing age was independently associated with laxative use after adjusting for gender, activities of daily living, cognitive function, number of active medical problems, medications taken, Italian region and length of stay. After excluding the prescriptions for hyperammoniemia, lactulose was the most frequently taken laxative (prevalence: 6.7% during hospital stay and 4.3% prior to hospital admission), followed by anthranoid laxatives such as senna, cascara, rhein and aloe (1.9% in-hospital and 3.3% pre-hospital). Other less frequently taken laxatives were picosulfate, phenolphthalein, lactitol, glycerol, bisacodyl and docusate. These patterns differ substantially from those reported by surveys conducted in other countries. Further studies are needed to assess the risks and benefits related to the intake of specific laxative ingredients.

It is argued that, in addition to investigations of life span parameters, a large number of biomedically important phenotypes can be profitably studied from a gerontological perspective. These would include "private" patterns of aging, especially in our own species, which exhibits extraordinary genetic heterogeneity. These, as well as a number of relatively common age-associated phenotypes, have been comparatively neglected by the gerontological community, and therefore warrant the designation as "orphan" phenotypes. From a tabulation of examples from each of the major body systems, five are elaborated upon: "hyperhippocampals," defined as individuals with intrinsically enhanced functional reserve in relevant neural circuitry; patients with a heterogeneous set of pathologies collectively referred to as "normal pressure hydrocephalus"; patients with late life activation of herpes zoster; individuals with unusually early onset of loss of olfactory function; and geriatric subjects with unusual sensitivity to "jet lag."

Although diet influences basic aging processes as well as age-associated disease processes, diet is either not mentioned or inadequately described in reports of gerontologic studies using animal models. Studies carried out in our laboratory with male F344 rats are a good example of the importance of diet in the use of an animal model for aging research. Nephropathy, resulting in kidney failure, is often an overwhelming disease problem in life span studies using ad libitum fed male F344 rats. However, by appropriate choice of dietary components, nephropathy can be reduced to only one of several disease processes contributing to the death of these ad libitum fed rats. Such diets greatly increase the value of the male F344 rat as a model for aging research. Because almost all rodent species and strains suffer from one or more major age-associated diseases, nutritional conditions should be sought in the case of each to minimize the occurrence of such diseases during an aging study. Restriction of energy intake (often called food restriction or dietary restriction) delays or prevents most age-associated disease processes in a spectrum of rat and mouse strains. It is, therefore, suggested that the dietary restricted rodent be used as the standard or base model for aging research. Moreover, dietary restriction is proving to be a powerful tool for the study of aging processes.

Human cells grown in culture exhibit exponential growth provided they are regularly provided with fresh medium. This exponential growth is limited, and although the cells eventually cease to divide, they remain viable for long periods of time. Such a culture is deemed to be "senescent", but it is not clear whether this reflects the growth pattern of cells in vivo. Considerable evidence has been obtained to correlate cell senescence in vitro with aging in vivo, but there is no convincing evidence that any organ or tissue ages as a result of senescence of its individual cells. Recently gained insights into the control of cell proliferation through studies of cell senescence, and the relevance of cell senescence as a strategy to prevent carcinogenesis are of particular interest.

This review of gerontological theory cites diverse examples of neural and endocrine involvement in the senescence of mammals and some other multicellular species that suggest fundamental involvement in age-related changes in cell functions. The data support the major hypothesis that age-related changes are generally caused by specific physiological factors that are extrinsic to cells. The success of these manipulations includes retarding or reversing specific age-related changes, and extending the life span. From another perspective, these findings have converted time in the analysis of senescence from an independent variable to a dependent variable. So far, we do not need to hypothesize any new mechanism that is not already known in disease or normal functioning.

There are advantages and disadvantages to all animal models for aging research. Investigators need to understand these issues as well as the nature of each relevant model, in order to choose the best model for their research. There is no "best" or "worst" model for aging research. Five genetically defined rodent models of potential utility in aging research are: 1. Inbred strains and F1 Hybrid mice and rats; 2. Single gene mutations and other single locus effects; 3. Congenic lines; 4. Recombinant Inbred (RI) strains; 5. Genetically selected strains and stocks. Animals of each of these types are available for research, but only inbred and F1 hybrid mice and rats are commercially available as aged animals. A general understanding of the need for careful genetic definition and for the best available barrier-breeding facilities has improved the quality of aging research significantly in the last two decades.