Premature Aging Process Research Articles

The Premature-Aging Process and New Functional Losses among People with Chronic Disabilities

The Premature-Aging Process and New Functional Losses among People with Chronic Disabilities

Premature aging‐like phenotype in fibroblast growth factor 23 null mice is a vitamin D‐mediated process

Fibroblast growth factor 23 null mice (Fgf-23-/-) have a short lifespan and show numerous biochemical and morphological features consistent with premature aging-like phenotypes, including kyphosis, severe muscle wasting, hypogonadism, osteopenia, emphysema, uncoordinated movement, T cell dysregulation, and atrophy of the intestinal villi, skin, thymus, and spleen. Furthermore, increased vitamin D activities in homozygous mutants are associated with severe atherosclerosis and widespread soft tissue calcifications; ablation of vitamin D activity from Fgf-23-/- mice, by genetically deleting the 1alpha(OH)ase gene, eliminates atherosclerosis and ectopic calcifications and significantly rescues premature aging-like features of Fgf-23-/- mice, resulting in prolonged survival of Fgf-23-/-/1alpha(OH)ase-/- double mutants. Our results indicate a novel role of Fgf-23 in developing premature aging-like features through regulating vitamin D homeostasis. Finally, our data support a new model of interactions among Fgf-23, vitamin D, and klotho, a gene described as being associated with premature aging process.

The multiple facets of premature aging in rheumatoid arthritis.

Among the processes that characterize aging in normal individuals, the best documented include atherosclerosis, osteoporosis, sleep disturbance, and muscle wasting, as well as others (Table 1). Over the course of 30 years, premature atherosclerosis has been recognized as an important factor in the morbidity and mortality of patients with systemic lupus erythematosus (1). This has been attributed to vasculitis and corticosteroid use in these patients. Today, the phenomenon of premature atherosclerosis is observed in many different chronic inflammatory diseases with an increased proinflammatory load independent of glucocorticoid therapy (ref. 2; see refs. at URL in Table 1 footnote). A recent study in female patients with rheumatoid arthritis (RA) demonstrated adjusted relative risks of myocardial infarction of 2.0 (for all women with RA) and 3.1 (for women with a disease duration of at least 10 years) (3). Overall, patients with RA were at significantly higher risk of death, with an adjusted relative risk of 1.27 (4). With respect to osteoporosis, a similar premature aging process is now being recognized in a variety of chronic inflammatory diseases independent of administered glucocorticoids (see refs. at URL in Table 1 footnote). As the result of our understanding of anti–tumor necrosis factor (anti-TNF) strategies, we observe that this particular molecule and TNF-inducible proinflammatory downstream molecules contribute strikingly to accelerated aging phenomena (e.g., see ref. 5). In chronic inflammatory diseases, it seems that the initial proinflammatory load has a general impact on premature aging, which affects organ systems such as the endocrine system and the neuromuscular system. In this review, with the main focus on RA, we want to demonstrate the following:

Neurofilaments of Klotho, the mutant mouse prematurely displaying symptoms resembling human aging.

We reported previously that neurofilaments (NFs) of aged rats were highly packed in the axon and contained a smaller amount of NF-M as compared with those of young rats (Uchida et al. [1999] J. Neurosci. Res. 58:337-348). We studied NFs of the mutant mouse, named Klotho, which displays prematurely symptoms resembling human aging. The transport of axonal cytoskeletal proteins, including NFs, tubulin and actin, was decreased at the leading portion of the peak of transported proteins in Klotho during the process of premature aging. The nearest neighbor inter-NF distance in Klotho axons (35-39 nm) was shorter than that of the wild-type mouse (48-49 nm), indicating the packing of NFs in Klotho. The ratio of NF-M to NF-L was slightly decreased in cytoskeletons from the spinal cords of Klotho. These changes are similar, though not identical, to those observed in aged rats, and are the first evidence of age-related changes in the neurons of Klotho.

A comparative analysis of the proteins between the fibroblasts from Werner's syndrome patients and age-matched normal individuals using two-dimensional gel electrophoresis

Werner's syndrome (WS) is an autosomal recessive disorder causing symptoms of premature aging. The fibroblasts of WS patients have a shorter life-span than normal fibroblasts. We analyzed the fibroblast proteins from three WS patients and from three age-matched normal individuals using two-dimensional gel electrophoresis and image processing. The expressions of 12 proteins were shown to be augmented or suppressed in WS fibroblasts compared with normal fibroblasts: 11 of 12 spots on the electrophoresis gel of WS fibroblasts were denser than the corresponding spots of normal individual fibroblasts, while the remaining one spot was fainter in WS fibroblasts than in normal fibroblasts. The abundance of these proteins were compared to those of the corresponding proteins from normal fibroblasts at various cell passages in vitro reported in the TMIG-2DPAGE database. The result shows that the change in the protein patterns in in vitro aging did not necessarily correspond to the change in WS fibroblasts, except for three proteins abundant in WS fibroblasts, which increased their abundance during in vitro aging. These results suggest that the premature aging process of WS fibroblasts shares only part of the in vitro aging process of normal fibroblasts.

Premature aging in Werner's syndrome spares the central nervous system

Werner's Syndrome is a rare genetic disease, characterized by premature aging of many tissues and organs. We studied the brain morphology and function in two patients with Werner's syndrome to assess the possible involvement of the central nervous system in this premature aging process. The two patients (brother and sister, respectively) were studied by magnetic resonance imaging (MRI) and angiography (MRA), single photon emission computed tomography (SPECT) with ( 99mTc)- d,l-hexamethyl propilene amine oxime (HMPAO), positron emission tomography (PET) with 2( 18F)-Fluoro-2-deoxyglucose (FDG), electroencephalography (EEG), and electromyography (EMG). Some of these investigations were also repeated after 1 year. The results of all these studies were normal. The premature aging process in patients with Werner's syndrome, while affecting most tissues, seems to spare the central nervous system.

Differential diagnosis and treatment of depressive features in Down's syndrome: A case illustration

A 21-year-old young man with Down's syndrome presented with depressive symptoms and intermittent features of a Parkinsonian like syndrome. After treatment with amitriptyline for 18 months he slowly improved and almost regained his former personality. Neither imaging procedures nor clinical features were able to establish a definitive cause of this patient's depression. There was no evidence of either neurodegenerative or premature aging processes. Discussion focused on increasing clinicians' awareness of frequently undiagnosed but treatable depressive disorders within the Down's syndrome population.

Genetic and clinical patterns of heritable cerebellar ataxias in adults. II. Clinical manifestations.

Clinical data on 244 probands with spinocerebellar types, 163 with late cortical cerebellar atrophies (LCCA), and 180 with olivopontocerebellar atrophies (OPCA) were analysed. Spinocerebellar cases were divided into three according to their estimated genetic mechanisms: recessive, dominant, or sporadic. Ages of onset were identical in sporadic spinocerebellar types, LCCA, and OPCA, the average being about 50. They showed highly correlated clinical patterns. In the light of other evidence, these diseases may represent a premature aging process in the central nervous system, probably determined multifactorially. Recessive spinocerebellar cases were very few. There were 127 cases of spinocerebellar types with dominant inheritance, characterised by age of onset around 33, colourful ocular signs, and spasticity. A large family with this disease was described in which 34 patients were affected through five generations. The computed tomograms showed an almost normal cerebellum and electronystagmograms indicated patterns of vestibulocular impairment. No necropsied case was available among the present material, but in pathological reports of similar cases, major lesions were found in the ventral and the dorsal spinocerebellar tracts, Clarke's columns, and the posterior columns in the spinal cord. This disease, or hereditary spastic ataxia, represented a fairly well-defined entity inherited dominantly among a group of cases with spinocerebellar types, and it was separable from LCCA or OPCA, not only on clinical and genetic grounds, but by a predominantly spinal involvement.

Beeinflussung der Blattzellen vonFontinalis antipyretica durch den Bewuchs vonCocconeis placentula

In a special habitat near Lunz (Mittersee) long time epiphytism ofCocconeis placentula var.tenuistriata and var.klinoraphis onFontinalis antipyretica leaves causes characteristic, strongly localized alterations in the walls of affected cells. They turn brown, may thicken, and may produce cystolithe-like protuberances into the cell lumina. These reactions obviously are brought about by a specific property ofCocconeis, for other epiphytes do not cause any change. The comparison of theCocconeis vegetation on younger and olderFontinalis leaves shows a considerable variability of the reactions mentioned, and in another habitat none could be found. Apparently several factors cause these reactions. Altogether,Cocconeis placentula is not a completely harmless epiphyte under certain circumstances. The alterations of the moss cells may be interpreted partly as a premature aging process, partly as a defensive action corresponding to alterations induced by some parasitic fungi. Furthermore, the reactions ofCocconeis onFontinalis are remarkably parallel to the influence of the dinococcalean algaRaciborskia inermis onSpirogyra grevilleana.