A cross-sectional survey was made in 56 exceptionally healthy males, ranging in age from 20 to 84 years. Measurements were made of selected steroidal components and peptidic hormones in blood serum, and cognitive and physical tests were performed. Of those blood serum variables that gave highly significant negative correlations with age (r > ؊0.6), bioavailable testosterone (BT), dehydroepiandrosterone sulfate (DHEAS), and the ratio of insulinlike growth factor 1 (IGF-1) to growth hormone (GH) showed a stepwise pattern of age-related changes most closely resembling those of the age steps themselves. Of these, BT correlated best with significantly age-correlated cognitive and physical measures. Because DHEAS correlated well with BT and considerably less well than BT with the cognitive and physical measures, it seems likely that BT and͞or substances to which BT gives rise in tissues play a more direct role in whatever processes are rate-limiting in the functions measured and that DHEAS relates more indirectly to these functions. The high correlation of IGF-1͞GH with age, its relatively low correlation with BT, and the patterns of correlations of IGF-1͞GH and BT with significantly age-correlated cognitive and physical measures suggest that the GH-IGF-1 axis and BT play independent roles in affecting these functions. Serial determinations made after oral ingestion of pregnenolone and data from the literature suggest there is interdependence of steroid metabolic systems with those operational in control of interrelations in the GH-IGF-1 axis. Longitudinal concurrent measurements of serum levels of BT, DHEAS, and IGF-1͞GH together with detailed studies of their correlations with agecorrelated functional measures may be useful in detecting early age-related dysregulations and may be helpful in devising ameliorative approaches.
MethodsThe patient group consisted of 95 subjects with AD (44 males and 51 females): 34 were obtained from the Cardiff Memory Clinic; 28 were the first sampled members of families with more than one case of late onset AD; and 33 were recruited from local psychogeriatric hospitals. The mean age of the patient group was 73-5 years (SD 101) with a mean age of onset of 67-5 years (SD 9-3). The majority of patients had an age of onset greater than 65 years (n = 56). Patients met the NINCDS criteria for probable AD.'" An age matched control group consisting of 86 subjects was obtained from the community with the help of a local general medical practice who identified elderly non-demented persons from their practice records. Potential controls were screened with the Minimental State examination'6 and included if they scored 28 or higher. The mean age of the control group was 73-2 years (SD 6 07). All patients and controls were white.With the approval of the local ethics committee and the consent of the patient's nearest relative, a sample of venous blood, anticoagulated with EDTA, was taken and DNA extracted from the white cells by a standard procedure. Digestion of the DNA and Southern blotting were also carried out by standard procedures. The Apo CII cDNA probe used was a 440 bp cDNA insert,'7 which detects allelic fragments of 3-8 kb and 3-5 kb, designated Al and A2 respectively, after digestion with TaqI. PCR analysis of apolipoprotein E genotypes was carried out by the method of Wenham et al. '8 Differences in allele and genotype frequencies were analysed by the method of Woolf.'9 The observed and expected genotype frequencies were compared in order to ensure that the loci were in Hardy-Weinberg equilibrium (HWE) using a X2 goodness of fit test. For the Apo E polymorphism, alleles 2 and 3 were collapsed because of small cell sizes. Haplotype frequencies were estimated according to a
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.