In order to investigate the changes with age in the function of respiratory center, we examined ventilatory response in healthy volunteers at rest and during exercise. Minute ventilation (V_E), ventilatory occlusion pressure (P_0.1) and breathing pattern were measured at rest in younger subjects (Y, n=19), middle aged (M, n=118) and the elderly (O, n=14). There were no significant differences in these three groups for V_E and P_0.1 while breathing room air. Both V_E and P_0.1 were increased in linear fashion with higher end-tidal P_CO2 when the subjects were placed on CO₂ rebreathing circuit. The ventilatory response to CO₂, evaluated by comparing the mean value of the slopes of these linear regression, were not significantly different among Y, M, and O group. When V_E slope and P_0.1 slope were tested for linear correlation with age, only the former was proved to be significantly related with age. Then fifty subjects (Y 22, M 15, O 13) undertook incremental exercise test on a bicycle ergometer. Ventilatory responses were individualy evaluated by the slope of linear regression line for V_E vs V_O2 (ΔV_E/ΔV_O2) and V_E vs V_CO2 (ΔV_E/ΔV_CO2). The mean ventilatory response for O group was significantly greater than those found in Y and M groups. The P_0.1 at the load of 75 watts as well as mean ventilatory response were also correlated positively with age. No significant correlation was found between P_0.1 observed in CO₂ rebreathing at rest and ventilatory response during exercise in Y, M or O group. From these results, we conclude that: 1) the effects of aging on respiratory contral during rest and exercise were not the same. 2) the greater response among elderly seemed to compensate for less effective gas exchange due to increased dead space by helping these subjects to overcome larger inspiratory impedance. This compensatory adaption may be instrumental for the preservation of normal blood gas during exercise. 3) ventilatory response to CO₂ rebreathing at rest showed no significant correlation with that observed during incremental exercise. This relationship was not influenced by aging of the subjects.

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In order to assess the prognosis of the lower extremity function and factors interfering with rehabilitation in patients with postapoplectic hemiplegia in relation to aging, 98 patients ranging in age between 43 and 87 years with fixed lesions measuring less than 15mm in actual size in the unilateral posterior limb of the internal capsule in the brain CT scan were analyzed and the following results were obtained. I. Prognosis of the lower extremity function: 1) Incidence of walking by oneself decreased (p<0.01) and gait disturbance increased (p<0.05) with aging, suggesting a major influence of aging. 2) The qualitative content of walking by oneself (a rate occupying walking with the assistance of a cane and outdoor walking by oneself) decreased with aging (p<0.05), with a tendency towards sudden decrease in the octogenarians. The object of rehabilitation in the majority of the octogenarians appears to be the return to home life and independence of the activities of daily living. 3) As to the site and size of the lesions, the prognosis in patients with the lesion in the posterior one-half of the posterior limb of the internal capsule was unfavorable regardless of the size of the lesion (p<0.05). 4) No difference was noted according to the disease type of cerebral hemorrhage and infarction and side of hemiplegia. II. Factors interfering with rehabilitation: 1) Incidence of the reduction of muscle strength on the uninvolved side, decrease of volition, urinary incontinence and dementia showed a positive correlation with age (p<0.05). The first two increased in the octogenarians and the latter in the seventies. 2) In the octogenarians, the reduction of muscle strength on the uninvolved side, decrease of volition and urinary incontience were correlated with the prognosis of the lower extremity function (p<0.05). Dementia only showed a tendency of correlation (p<0.2). The former 3 factors were intimately correlated with gait disturbance in the prognosis of the lower extremity function (p<0.01). Dementia, on the other hand, showed a negative correlation with walking by oneself (p<0.05). 3) The muscle strength on the uninvolved side in the octogenarians rapidly and readily decreased on acute bedridden state, so that rehabilitation measures should be taken as quickly as possible. The factors interfering with rehabilitation including aging are closely related to one another, and it appears quite rare that one of these factors alone determines the prognosis of the lower extremity function.

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Blood samples taken during all months of the year from 75 healthy aged females, aged over 60 years, were examined for serum concentrations of PTH, 25-OHD, 24, 25(OH)2D, 1, 25(OH)2D, calcium (CA) and inorganic phosphate (Pi). The radial mineral content (RMC) was also measured by single photon absorptiometry on the same day the blood samples were obtained. From the analysis of probability assuming a normal distribution, the normal range of each hormone in the healthy aged female was calculated as follows;
25-OHD; 13-39ng/ml
24, 25(OH)2D; 1.0-3.3ng/ml
1, 25(OH)2D; 11-55ng/ml
PTH; 0.16-0.55ng/ml
Serum PTH levels showed the significant correlation between 25-OHD (r=-0.363, p<0.01), 24, 25(OH)₂D (r=0.263, p<0.05) and age (r=0.223, p<0.05). The significant positive correlations between serum levels of calcium and 25-OHD (r=0.422, p<0.01), 24, 25(OH)₂D (r=0.280, p<0.05), 1, 25(OH)₂D (r=0.359, p<0.01) and RMC (r=0.360, p<0.01) were found. Significant positive correlation between RMC and 25-OHD (r=0.346, p<0.01), 24, 25(OH)₂D (r=0.321, p<0.01) and calcium (r=0.360, p<0.01) were also found. Thus, vitamin D metabolites might play an improtant role in the maintenance of serum calcium levels and of mineral content in the aged healthy females.

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It is not rare that some gastric cancers in the elderly patients reveal a rappid growth, even if they have commonly a slower growing tendency than that of young patients. Three hundred and six cases of gastric cancer were encountered from 2000 consecutive autopsy cases, which involve 945 cases of the patients who have their daily lives in the facilities for the aged, with relatively homogenous circumstances. Excluding the cases of which the histological diagnosis were not confirmed, 279 cases with 313 cancer lesions were served as the materials for this study. The histological types of cancer lesions are commonly divided in two criterias:“differentiated type” and“undifferentiated type”. In early cancer group of our cases, 97% of lesions have had the differentiated type carcinomas, whereas only 63% of lesions in advanced cancer group was that type. Applying this method of classification not only to the early stage but also to advanced stage, the distribution of histological types of gastric cancer of the aged showed the differentiated type in 75%, and the undifferentiated one in 25% respectively. From these above data, the progress ratio of undifferentiated type cancer to differentiated type one would be calculated as follows:
(D)×(t₁/t₂)DE/UE t₁/t₂=9.1
D: total number of differentiated carcinoma cases
U: total number of undifferentiated carcinoma cases
t₁: time being required to progress from early to advanced stage in differentiated carcinoma
t₂: time being required to progress from early to advanced stage in undifferentiated carcinoma
DE: differentiated carcinoma cases in early stage
UE: undifferentiated carcinoma cases in advanced stagee
The time which the differentiated type carcinoma needs to progress from early to advanced stage would be about 9.1 times of the one in the undifferentiated type carcinoma.

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This paper describes clinical features of high renin hypertension in the elderly. Peripheral plasma renin activity which was measured in 59 hypertensive patients aged 70 to 85 under the standard condition ranged 0 to 20.1ng/ml/hr. All 59 patients were divided into 9 with plasma renin activity of 3.0ng/ml/hr or more (high renin group) and the remaining 50 with plasma renin activity of less than 3.0ng/ml/hr (control group). The developing pattern of hypertension differed between the two groups. Six of the high renin group (66.7%) had a history of abrupt rise of blood pressure, while only 3 of the control group (6.0%) had it (p<0.01). The frequency of diastolic blood pressure of 100mmHg or more, massive proteinuria, hypokalemia and hypercholesterolemia were significantly greater in the high renin group than in the control group respectively. The incidence of arterial bruit, a physical sign of moderately severe stenosis, over eyeballs, carotid arteries, abdomen or femoral arteries, and that of vascular complication such as stroke, ischemic heart disease or intermittent claudication were also significantly greater in the high renin group than in the control group. Definite or suspected renovascular hypertension was found in 6 of the high renin group (66.7%) but only in 1 of the control group (2.0%) (p<0.01). These results indicate that the high renin hypertension in the elderly strongly suggests the presence of renal artery stenosis associated with generalized atherosclerosis.

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Six cases of cardiac amyloidosis causing heart failure were found among 3, 700 consecutive autopsy of the aged, with an incidence of 0.2%. Their ages ranged from 60 to 90 (mean 80) years old. Clinical diagnosis was ischemic heart disease in 4 cases, amyloidosis by rectal biopsy in 1, and myopathy in 1, who was proven to have multiple myeloma in autopsy. All six cases suffered from congestive heart failure, 3 cases died of a sudden, including 2 cases of digitalis intoxication. Chest X-ray films showed cardiomegaly (over 55% in CTR) in 5 cases. Electrocardiograms showed myocardial infarction pattern in 4 cases, left axis deviation in 5, low voltage in limb leads in 4, transient atrial fibrillation in 2, atrial flutter in 1, sinus arrest with escape beat in 1, alternating bundle branch block in 1. Echocardiogram was recorded in 3 cases, which showed dilatation of the left atrium, hypokinesis of left ventricular wall. Cardiac index was low in 2 of 4 cases. ²⁰¹Tl-sintigram showed partial defect of uptake in 2 of 4 cases. Gross pathologic findings were firm atrial endocardium with amyloid nodules and fibroelastosis. The mean heart weight was 433g; in 3 cases it was 230∼350g, which had dominant amyloid deposits in the atrium. In the other 3 cases heart weight was 550∼590g, which had dominant amyloid deposits in the ventricular walls. We classified the former as the atrial type, and the latter as the ventricular type. Both atria were dilated in 4 cases. Two cases of ventricular type were associated with severe coronary stenosis, which showed dilatation of both ventricles. Cases of ventricular type were all misdiagnosed as myocardial infarction during life. Amyloid deposits were found in the endocardium, myocardial interstitium, intramural coronary vessel walls, but not found in the major epicardial coronary arterial walls. All six cases were considered as primary amyloidosis except 1 case of myeloma. The affinity of amyloid for Congo red dye after exposure to potassium permanganate did not change in all 6 cases.

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The purpose of this investigation was to compare monocyte functions in lymphocyte activation between old individuals over 70 years and young under 35 years. In order to examine that peripheral blood lymphocyte (PBL) responsiveness to mitogen is monocyte dependent, monocyte-depleted PBL was cocultured with monocyte in the presence of pokeweed mitogen (PWM) or concanavaline A (Con A). Lymphocyte responsiveness to PWM was evaluated by thymidine uptake after 3 days of culture and immunoglobulin G (IgG) production after 8 days of culture, and lymphocyte activation by Con A was evaluated by thymidine uptake after 3 days of culture. The incorporation of thymidine uptake and IgG production by monocyte-depleted PBL was very low. A significant increase of thymidine uptake and IgG production was observed in cultures with added monocyte. These results indicated that lymphocyte responsiveness to PWM and Con A is monocyte-dependent. Thymidine uptake annd IgG production by PBL were compared between PBL/“old”monotype combinations and PBL/“young” monocyte combinations in the presence of PWM or Con A. The incorporation of thymidine by PBL/“old”monocyte combinations after 3 days of culture was lower than PBL/“young” monocyte combinations. PBL/“old” monocyte combinations showed a lower production of IgG than PBL/“young” monocyte combinations. But when the number of monocyte added to culture was 5×10⁴/0.2ml, IgG production was no difference among two groups. These results suggest that a part of helper function of “old” monocyte to PBL was impaired.

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In view of the rapid lengthning of human lifespan, it is important to consider what kinds of conditions the very elderly require to maintain, physical, mental and social health. Healthy centenarians provide adequate research material to clarify the determinants of the physiological phenomenon of highly advanced age. It is commonsense to consider that longevity is obtained by interaction of hereditary and environmental factors. The main purpose of this paper is to make clear whether or not hereditary factors are involved in attainment of longevity. There have been many papers reporting longeval persons having longeval ancestors and offspring in their pedigree. Most of them are merely reports of facts and are not able to prove that longevity comes from longeval families. One paper (Abbott, 1974) reported a controlled case study directed at this proof but selection of control cases, it can be pointed out, was affected by some biassed factors. We, however, have adopted the following strict conditions for the selection of control cases: The control case (1) must be born and raised and must die in the vicinity of the centenarian's residence; (2) must be the last or the second last of siblings; (3) must be older than the average Okinawan lifespan (at present older than 75 years in males and 82 years in females); (4) must have the eldest sibling live to between 100 and 105 years old, if alive; (5) must be mentally alert enough to understand our questions and give satisfactory answers; and (6) must have at least three siblings who died from known cause other than suicide, homicide, ccident and war trauma. By using these criteria, only eleven cases were selected out of 2270 elderly people (more than 65 years old). Various indices of longevity were calculated between centenarians and control families in each separate group of family members: fathers, mothers, male siblings, female siblings, total siblings and total family members. In conclusion, these results show that factors influencing longevity are inherited mainly through the female line but some are also inherited through the male line. It cannot be forgotten that children are strongly influenced by their mothers in lifestyle and habits during their growth and maturity. In view of these facts, HLA examinations were essential to confirm the hereditary basis of longevity.

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