Genetic programs and age-dependent changes in DNA and protein are involved in aging. The genetic program governs body weight, longevity, aging rate, sex-maturating period and metabolic rate in mammals, and such a number of life history variables are highly correlated with body size. Monogenic age-1 and daf-2 C. elegans mutants extend life span twice. However, human monogenic progeroids shorten lifespan. The Werner syndrome gene was mapped on 8p12. Mutations in the Cockayne syndrome genes (the CSA and CSB genes acting for preferential repair of active genes by interacting with transcription factor TFIIH) and in the ataxia telangictasia gene ATM (homologous with PI-3 kinase for signal transduction) have been disclosed. All such findings suggest a strong basis for the genetic program of aging. In addition, recent evidence indicates that genetic instability, such as telomere loss, somatic and mitochondrial DNA mutations, increases with age. In addition, amounts of carbonylated protein also increase during human aging, and greatly increase in an SOD-deficient C. elegans mutant, but to a less extent in long-living age-1. Therefore, the aging process involves gene action, genetic instablity and protein oxidation. Dietary restriction and elimination of deleterious excessive reactive oxygen species may improve many abnormalities due to aging.
Thrombomodulin (TM) is a thrombin receptor on endothelial cells. When endothelial cells are damaged TM is degraded and released into the blood. We examined whether levels of TM in plasma reflect endothelial damage related to aging. We measured the TM level in samples of plasma from 93 healthy men aged from 22 to 81 years. None had hypertension, obesity, diabetes mellitus, or cardiovascular disease. The relationship between the level of TM (Y) and age (X) could be approximated by Y=0.176X+10.379, the correlation was significant (r=0.647, p<0.01). Basal levels of TM in subjects from 20 to 60 years old showed a gradual increase, that was not statistically significant. Basal concentrations of TM were significantly higher in the older subjects than in the younger subjects. The high levels of TM in the older subjects might reflect endothelial damage. In conclusion, a high TM level in plasma may be a sign of endothelial damage related to aging.
Objective: To clarify the clinical and pathological characteristics of gastric cancer in the elderly. Method: Clinical and pathological characteristics of patients who died during 1986-94 with gastric cancer which did not undergo surgery were studied retrospectively. The patients were divided into three groups according to age: A (65-74 years, n=38), B (75-84 years, n=77), and C (85 years and over, n=43). Results: Borrman type-1 was more frequent in group C and Borrman type-4 was frequent in group B. “Early cancer”, protruded type (type I or type IIa) was more frequent in group C. In cases of advanced cancer some patients did not undergo surgery because the cancer was too advanced, and others had concomitant diseases that made surgery risky. In all groups, a few patients refused surgery. In cases of “early cancer”, the most reason for not undergoing surgery was a concomitant disease in all groups. Other reasons were general weakness and dementia in group C, second malignancy and dementia in group B, and second malignancy ingroup A. After advanced cancer was diagnosed, 9.6% survived for 1 year, and 1.7% for 2 years. After early cancer was diagnosed, 50.7% survived for 1 year, 15.2% for 3 years and 7.8% for 4 years. The survival rates did not differ by age. In all age groups, gastric cancer was frequently the main cause of death in patients with advanced cancer, but many patients with “early cancer” died of other causes.
The characteristics of multiple spongy necrosis of the basis pontis (MSN), central pontine myelinolysis (CPM), and cerebrovascular disease (CVD) of the pons developing in the elderly have not been fully clarified. We therefore studied 305 patients (aged 60-107, mean: 83.9) autopsied in Nagoya City Kohseiin Geriatric Hospital. MSN was found in four patients (1.3%). The major histologic finding was multiple necrosis of the basis pontis, characterized by loss of myelin and axons, no reactive astrocytes or inflammatory cells were found. Small foci of spongy necrosis appeared to unite with each other to form larger lesions. The central basis pontis was weakly stained by Klüver-Barrera stain in 15 patients, which suggested the presence of CPM. However, the diagnosis was only confirmed in one patient, (by the myelinolysis, loss of oligodendroglia, infiltration of macrophages, and reactive astrocytosis). With regard to CVD, none of the 305 patients had macroscopic pontine hemorrhage, but histologically small and old hemorrhagic lesions were found in 15. These lesions were associated with hypertensive or arteriosclerotic changes in the pontine vessels. Pontine infarction was evident in 77 patients (25.2%). In most lesions (74%) the area of infarction was smaller than 1mm2. In 27 of the 74 patients with lacunar or microscopic infarcts, the pontine infarcts were found in areas where the blood was supplied through the short circumferential branch.
A 63-year-old woman was admitted to the hospital because of swelling of both forearms and muscle weakness in the limbs. Laboratory examination revealed abnormally high levels of serum creatine kinase, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, and lactate dehydrogenase. Polymyositis was diagnosed, and prednisolone was administered. Her condition had been well controlled on prednisolone until several months before admission, when bilateral blepharoptosis and diplopia developed. An edrophonium test was positive: muscle weakness was transiently alleviated. High titers of anti-acetylcholine receptor antibodies were found. A chest CT scan showed a mass in the anterior part of the mediastinum. We diagnosed myasthenia gravis associated with thymoma. After an extended thymectomy, the patient's condition improved. When muscle weakness recurs after remission of polymyositis, myasthenia gravis should be considered.
A 90-year-old woman was admitted to our hospital in December 1993 because of dyspnea on exertion and malaise. She had been well until October 1993, when she first noticed Raynaud's phenomenon, skin tightening, digital ulceration and scarring of her hands. On physical examination, generalized edema was found, along with acrosclerosis with contracture, especially in the fingers, wrists, and elbows. Inspiratory crackles were noted. A roentgenogram of the chest and an echocardiogram revealed pulmonary fibrosis, pulmonary congestion, and massive pleural and pericardial effusions. The pleural effusion was a transudate. Progressive systemic sclerosis was diagnosed, and furosemide and isosorbide were given. The edema and pulmonary congestion resolved, but the pleural and pericardial effusions did not. Prednisolone was given, which reduced the pleural effusion but not the pericardial effusin. The pleura and the pericardium are not usually involved in progressive systemic sclerosis, and this disease rarely occers in patients over 70 years old. To the best of our knowledge, this was one of the oldest patients with progressive systemic sclerosis. The combination of masive pleural and pericardial effusions, and the advanced age of onset make the present case unusual.
To help plan for the future of undergraduate education in geriatric medicine in Japan, we reviewed the literature concerning undergraduate teaching of geriatric medicine in western countries. Undergraduate teaching in geriatric medicine in the UK is well developed: 22 of 25 universities have a full department of geriatric medicine. Training in geriatric medicine is mandatory in almost all universities. In contrast, geriatric medicine is an elective in most universities in the US. There is a shortage of geriatric medicine faculty in the US, which is similar to the situation in Japa. Clinical and basic research in geriatric medicine and gerontology should be encouraged to attract persons into this field.