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2.0 - 25th September 1997

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J Am Geriatr Soc 1997 Jul;45(7):813-817

Glucose metabolism in older adults: a study including subjects more than 80 years of age.

Garcia GV, Freeman RV, Supiano MA, Smith MJ, Galecki AT, Halter JB

Department of Internal Medicine, University of Michigan, Ann Arbor, USA.

OBJECTIVE: This study was undertaken to understand the dynamics of glucose metabolism in healthy non-diabetic subjects older than age 80 (old-old) compared with subjects aged 61 to 79 (young-old), as well as to compare healthy older subjects with impaired glucose tolerance (IGT) with older subjects with normal glucose tolerance (NGT). DESIGN: A cross sectional, observational study. SETTING: A university hospital clinical research center. PARTICIPANTS: There were 28 community-dwelling adults, 10 older than age 80 and 18 aged 61 to 79. Thirteen of these people had NGT and 15 had IGT. Subjects were not taking any medication that interfered with glucose tolerance. MEASUREMENTS: Status of glucose tolerance was determined by an oral glucose tolerance test categorized as NGT or IGT according to WHO criteria. Insulin sensitivity (SI) and glucose effectiveness (SG) were assessed using a tolbutamide-assisted intravenous glucose tolerance test (IVGTT). The data were analyzed using the Minmod modeling program. Glucose tolerance (K(g)) and the acute insulin response to glucose (AIRg) were calculated from the IVGTT. RESULTS: There were no significant differences between the young-old and old-old in body mass index or in plasma glucose, insulin, or C-peptide levels in the fasting state or during the OGTT. Values for K(g), SI, SG, and AIRg from the IVGTT were similar in the two age groups. When the subjects were classified by glucose tolerance status, the subjects with NGT had age, gender, and body mass index similar to the subjects with IGT. Older people with IGT had a lower K(g) and tended to have higher fasting glucose and similar fasting insulin compared with people with NGT. IGT subjects had lower SI and tended to have lower SG. The AIRg in IGT subjects tended to be low rather than high when compared with older people with NGT. CONCLUSION: Otherwise healthy adults more than 80 years of age have measures of glucose metabolism similar to people aged 61 to 79. The presence of IGT in older adults is associated with insulin resistance, regardless of patient age. We hypothesize that the lack of pancreatic islet compensation for insulin resistance may contribute to impaired glucose tolerance in older adults.


Curr Top Cell Regul 1997;35:107-121

Aging and regulation of apoptosis.

Warner HR

Biology of Aging Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.

When Lockshin and Zakeri discussed the relevance of apoptosis to aging, the common view was that apoptosis had primarily a negative impact on aging by destroying essential and often irreplaceable cells. That view has now changed to one that acknowledges that there are two general ways in which apoptosis can play a role in aging: (1) elimination of damaged and presumably dysfunctional cells (e.g., fibroblasts, hepatocytes) which can then be replaced by cell proliferation, thereby maintaining homeostasis and elimination of essential postmitotic cells (e.g., neurons) which cannot be replaced, thereby leading to pathology. Evidence exists in two systems (fibroblasts and thymocytes/lymphocytes) that there are age-related decreases in the potential for apoptosis, although the molecular bases for these decreases appear to differ (Table II). Fibroblasts (and neurons?) lose the ability to downregulate bcl-2 in response to an apoptotic signal; thus, apoptosis is blocked even though an initiating signal has been received. In contrast, thymocytes/lymphocytes lack the ability to initiate the signal due to downregulation of the cell surface receptor Fas. There is limited information available for other tissue types, and nothing is known about why and how these age-related changes occur. An interesting observation, but not necessarily a critical one, is that the frequency of upregulation of the bcl-2 gene due to chromosome translocation increases with age. The role of apoptosis in regulating cell number is also a promising area of research. The studies on liver damage and neoplastic lesions suggest an extremely important role for apoptosis in controlling cancer. This may be particularly important in the prostate, where hypertrophy and cancer are a virtual certainty with ever-increasing age. It is not known whether the ability to undergo apoptosis declines in the prostate with increasing age, but it appears likely that it does. One problem in answering questions about the actual regulation of apoptosis is the lack of a quantitative assay. Apoptosis appears to be either "on" or "off" in cells, while the basic cell-killing machinery may often be present, but in an inactive form. Most assays for apoptosis are microscopic rather than kinetic, and the rate-limiting step may be at the level of the initiating signal. Thus, if CR, which extends the life span of rodents, does upregulate apoptosis, it is not clear how to quantify the magnitude of this effect or what should be quantified. The best one can do is to measure the frequency of occurrence of apoptotic bodies. This is essentially a pool size assay which provides little knowledge about how rapidly cells are leaving and entering the pool. Nevertheless, the results currently available do suggest that apoptosis is a process which may be important in aging, at least in some tissues, and the mechanism of its regulation needs to be understood. Although a variety of tumor suppressor gene and oncogene products are known to be involved in signal transduction associated with apoptosis, it remains to be shown which of these, if any, are actually involved in "on-off" switches for apoptosis and which might regulate the intrinsic rate of apoptosis. As Driscoll has already pointed out: "regulation and execution of cell death is an absolutely critical process that interfaces with nearly every aspect of life. Future investigation of the links of cell death to cellular aging and the aging of organisms should be an exciting enterprise."


Exp Gerontol 1997 Jan;32(1-2):205-214

Diet and calorie restriction.

Sprott RL

Biology of Aging Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.

Current data suggest that the life spans of commonly held rodent species have decreased and the occurrence of tumors occurs earlier in the lifespan of ad libitum-fed animals. The most likely cause of this change in the life span of barrier-reared genetically defined animals is increased body weight. The effects of caloric restriction on a variety of functional measures and on age-dependent tumors and lesions are the focus of this presentation. Recommendations for caloric restriction, or at least "dietary control," will be discussed.


J Neurosci 1997 May 15;17(10):3710-3726

Purkinje cell survival and axonal regeneration are age dependent: an in vitro study.

Dusart I, Airaksinen MS, Sotelo C

Institut National de la Sante et de la Recherche Medicale U106, Hopital de la Salpetriere, 75651 Paris Cedex 13, France.

Purkinje cells are among the most resistant neurons to axotomy and the most refractory to axonal regeneration. By using organotypic cultures, we have studied age- and environment-related factors implicated in Purkinje cell survival and axonal regeneration. Most Purkinje cells taken from 1- to 5-d-old rats, the period in which these neurons are engaged in intense synaptogenesis and dendritic remodeling, die 1 week after plating, whereas if cultured before or after this period, Purkinje cells survive, even in the absence of deep nuclear neurons, their postsynaptic targets. Cerebellar slices taken from 10-d-old rats and kept in vitro for 1 week acquire a cellular composition resembling mature cerebellum. Their Purkinje cells are resistant to axotomy, but even when confronted with permissive environments (sciatic nerves or fetal cerebellar slices), their axons do not regenerate. In contrast, fetal rat and mouse Purkinje cells are able to regenerate their axons on mature cerebellar slices. This regeneration is massive, and the regrowing axons invade all cerebellar regions of the apposed mature slices, including white matter. These results show that Purkinje cell survival and axonal regeneration are age-related and independent from environmental constraints. Moreover, our observations suggest strongly that the onset of synaptogenesis of Purkinje cell axons could provide a signal to turn off their growth program and that, thereafter, permissive microenvironment alone is unable to reestablish such a program.

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