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Diseases and aging: patterns of morbidity with age; relationship between aging and age-associated diseases.

Patterns of morbidity with age can be schematically represented in three situations: 1) as a progressive illness, such as Alzheimer's disease, leading to a relatively rapid functional decline. 2) as a catastrophic event, such as a stroke or hip fracture, leading to a decline in function with improvement after rehabilitation. 3) as normal aging with gradual progressive functional decline. Results from the New Mexico Aging Process Study provide some unique insights about the consequences of the effects of aging on the nutritional status of healthy elderly people. Between 1979 and 1989, anthropometric and biochemical markers as well as dietary intakes remained relatively constant in this healthy elderly population. Thus, the aging process alone may have little or no important consequences on the nutritional status of healthy elderly individuals. However, the adaptation of pancreatic and intestinal function to undernutrition and refeeding can be perturbed in these individuals.

Accidental Falls

"You're only as old as you feel": self-perceptions of age, fears of aging, and life satisfaction from adolescence to old age.

We examined differences in subjective age identification from adolescence to old age and the relation between subjective age and fears about one's own aging and life satisfaction. Using a questionnaire format, 188 men and women from 14 to 83 years of age made judgments about how old they felt, looked, acted, and desired to be. Respondents also answered questions about their personal fears of aging and present life satisfaction. Results revealed that individuals in their teens held older subjective age identities, whereas during the early adult years, individuals maintained same age identities. Across the middle and later adult years, individuals reported younger age identities, and women experienced younger age identities than men across these adults years. Results also revealed that discrepancies between subjective and actual age were associated with personal fears of aging and life satisfaction, especially in younger men and women.

Adolescent

Sociological research on age, aging and the aged in the Netherlands.

A review is given of the socio-gerontological research in the Netherlands. According to a frame work, organising this area of research, first an overview is presented of the studies on age and ageing and next the research on the aged is summarized. The research on age and ageing is limited. Some publications analyse the social meaning of age, some cohort studies have been conducted and recently the life course approach is getting attention. Concerning the research on the aged, the main areas studied are: living circumstances, age stratification, family and social contacts, housing, work and retirement, formal and informal care, death and dying. Since 1970 the amount of socio-gerontological research has increased. It became prominent in the eighties with the promotional activities of a special committee for gerontological research. Several universities are identified with their special areas in the sociology of ageing and the aged.

Adult

Interactions of aged gametes: in vitro fertilization using in vitro-aged sperm and in vivo-aged ova in the mouse.

A study of varying combinations of in vitro-aged sperm and in vivo-aged ova at 3 hr intervals from 0-24 hr resulted in failures at different steps of the fertilization process during in vitro fertilization of mouse ova. Significant decreases caused by sperm aging, ova aging, and sperm X ova aging interaction were found in sperm penetration. Pronuclear formation was not affected by sperm aging and was enhanced by ova aging, and there was a significant effect of sperm X ova aging interaction. Sperm aging significantly influenced the prometaphase stage of the fertilization process. Therefore, it is suggested that the detrimental fertilization effects resulting from aging gametes are due to different mechanisms in sperm and ova, that these mechanisms are affected at different times, and that they affect different steps in the fertilization process.

Aging

Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study.

To evaluate the hypothesis that endocrine profiles change with aging independently of specific disease states, we examined the age trends of 17 major sex hormones, metabolites, and related serum proteins in 2 large groups of adult males drawn from the Massachusetts Male Aging Study, a population-based cross-sectional survey of men aged 39-70 yr conducted in 1986-89. Group 1 consisted of 415 men who were free of obesity, alcoholism, all prescription medication, prostate problems, and chronic illness (cancer, coronary heart disease, hypertension, diabetes, and ulcer). Group 2 consisted of 1294 men who reported 1 or more of the above conditions. Each age trend was satisfactorily described by a constant percent change per yr between ages 39-70 yr. Free testosterone declined by 1.2%/yr, and albumin-bound testosterone by 1.0%/yr. Sex hormone-binding globulin (SHBG), the major serum carrier of testosterone, increased by 1.2%/yr, with the net effect that total serum testosterone declined more slowly (0.4%/yr) than the free or albumin-bound pools alone. Among the major androgens and metabolites, androstane-3 alpha,17 beta-diol (androstanediol; 0.8%/yr) and androstanediol glucuronide (0.6%/yr) declined less rapidly than free testosterone, while 5 alpha-dihydrotestosterone remained essentially constant between ages 39-70 yr. Androstenedione declined at 1.3%/yr, a rate comparable to that of free testosterone, while the adrenal androgen dehydroepiandrosterone (3.1%/yr) and its sulfate (2.2%/yr) declined 2-3 times more rapidly. The levels of testosterone, SHBG, and several androgen metabolites followed a parallel course in groups 1 and 2, remaining consistently 10-15% lower in group 2 across the age range of the study. Subgroup analyses suggested that obese subjects might be responsible for much of the group difference in androgen level. Serum concentrations of estrogens and cortisol did not change significantly with age or differ between groups. Of the pituitary gonadotropins, FSH increased at 1.9%/yr, LH increased at 1.3%/yr, and PRL declined at 0.4%/yr, with no significant difference between groups 1 and 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Subjective age, age identity, and middle-age adults.

A casual model of subjective age among middle-age working adults is proposed. Determinants of subjective age include chronological age, education, health, self-esteem, financial satisfaction, and job satisfaction. Life satisfaction is used as an explanatory outcome. Using a sample of middle-age men, the results indicate that self-esteem and financial satisfaction were important mediators between chronological age and subjective age. In turn, positive and negative characteristics were associated with both a "younger" and "older" subjective age. The results contribute to the further understanding of adult development and the meaning of subjective age.

Adult

Aging in the AXC/SSh rat: characterization of moderately abundant ventral prostate proteins showing age-dependent diminution and one protein exhibiting age-invariant content.

To determine whether prior demonstrations of age-related decrements in prostate content of minor, androgen regulated proteins represent a generalized phenomenon, we validated a denaturing polyacrylamide gel electrophoretic protocol for separation and quantification of moderately abundant ventral prostate cytoplasmic proteins. We established age-related, progressive 3- to 3.5-fold decreases in prostate content of proteins of 90, 79, 63, and 58 kDa and found that content of a 46 kDa protein was age-invariant. The amount of 90 and 46 kDa proteins was not significantly altered, whereas the level of 79, 63 and 58 kDa proteins decreased during 72 h post-orchiectomy of 3-month-old rats. Testosterone injection of intact 26-month-old rats caused an average 2-fold increase in 90, 79, 63, and 58 kDa protein content and did not affect 46 kDa protein level. Because we demonstrated the 46 kDa protein is not a secretory protein, absence of an affect of aging or testosterone on prostate content is not due to secretion mediated inaccessibility to intracellular processing. The apparent relation between age and prostate content of these proteins is not a consequence of potential age-related changes in ventral prostate cell content or distribution because biochemical and histologic analyses show this does not significantly occur. Our studies establish age-related decreases in ventral prostate content of moderately abundant, androgen responsive proteins and show that content of at least one protein is age- and androgen-independent. It remains to be determined whether these findings reflect direct effects of gene regulation.

Aging

Endosymbiotic theory of aging revisited: Age-related leakage of mitochondrial dsDNA/RNA stimulates cytosolic nucleic acid sensors which remodel the immune network and promote the aging process.

About 1.5-2 billion years ago, an endosymbiosis between aerobic α-proteobacteria and anaerobic archaeal cells generated mitochondria, i.e., organelles capable of producing oxidative energy. The bacterial genome was fundamentally reduced and a circular mitochondrial genome evolved containing mainly the genes coding for the subunits of the electron transport chain. Before the symbiotic event, there existed a virus-host co-evolution which involved the development of sensors for detecting dangerous viral DNA/RNA molecules. Endosymbiosis supplied eukaryotic cells not only with an oxidative powerhouse to allow the evolution of more complex multicellular organisms but it also meant that cells now housed an organelle which was able to generate reactive oxygen species (ROS) and to leak mitochondrial DNA (mtDNA) and double-stranded RNA (dsRNA) into the cytoplasm. There is now abundant evidence that during aging and age-related diseases mitochondria are prone to release both mtDNA and dsRNA. In the cytoplasm, mtDNA/dsRNA molecules activate a number of cytosolic nucleic acid sensors leading to the secretion of type-1 interferons (IFN) and many other cytokines which promote an age-related proinflammatory state. Currently, it is known that mtDNA can activate the cGAS-STING pathway, AIM2 inflammasomes, IFI16 receptors, and ZBP1 sensors and in addition mitochondrial dsRNA stimulates RIG-1/MDA5 signaling. Interestingly, there is abundant evidence that all these receptors are drivers of cellular senescence and inflammaging. For decades, there has been mounting evidence that mitochondria have a crucial role in the aging process. We will examine this question from the perspective of evolution and propose that mitochondrial evolution created an endogenic source for the leakage of dangerous mtDNA/dsRNA which subsequently stimulated cytosolic DNA/RNA sensors, an evolutionarily conserved viral defence mechanism. It seems that these two evolutionary events provided not only the basis for the inevitable process of aging but also ensuring the death of parental organisms.

Aging

[Maturescence, a critical phase between ages 40 and 65. Health, illness, aging and social ages].

The recent emergence of a critical phase in life called maturescence, situated between the ages of 40 and 65, is a by-product of social life in industrialized societies. Because it is considered as a crossroads, this phase in life is not connected with any particular chronological age, such as reaching forty or fifty. Rather, it involves the difficulties of aging in society and the oncoming of identity conflicts, all of which must be seen in relation with the specific health-related problems that result from aging.

Adult

Excessive testicular progesterone secretion in aged male Fischer 344 rats: a potential cause of age-related gonadotropin suppression and confounding variable in aging studies.

Previous studies have inconsistently reported elevated sex steroid levels in aging male F344 rats, which frequently develop testicular Leydig cell tumors. The aims of this study were to characterize circulating steroid levels and to determine the in vivo source and functional significance of altered steroid secretion in these animals. Progesterone (P) and to a lesser extent estradiol (E2) levels were increased, while gonadotropins and testosterone (T) were decreased, in intact 24-mo-old compared to 12-mo-old rats. P levels were inversely correlated with gonadotropins and T. All old rats demonstrated Leydig cell hyperplasia or tumors. After orchidectomy, P levels were markedly decreased. Gonadotropin levels were similar in orchidectomized 24-mo compared to 3-mo-old rats. We conclude that the testis is the source of excessive P and E2 secretion in vivo in old F344 rats. Increased P (or E2) negative feedback may contribute to the suppression of gonadotropins and reproductive function in aging male F344 rats. Finally, excessive P secretion may be a confounding pathological variable in aging studies using this rat model.

17-alpha-Hydroxyprogesterone

Postnatal age and the metabolism of medium- and long-chain fatty acids by isolated hepatocytes from small-for-gestational-age and appropriate-for-gestational-age piglets.

Hepatocytes were isolated from full-term small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) piglets at 6 or 48 h postpartum and incubated with 1 mmol/L [1-14C]-octanoate (8:0), -nonanoate (9:0) or -oleate (18:1). The cells oxidized [nmol 1-C/(h.10(6) cells)] 9:0 to carbon dioxide (12.5) and acid soluble products (28.9) faster than 8:0 (10.9, 20.6, respectively), and both were oxidized faster than 18:1 (3.9, 9.9) regardless of the piglet age or weight. Oleate accumulated in lipid products eightfold faster than did 8:0 and 9:0. No differences between cells from SGA and AGA piglets were detected. Recovery of 1-C in CO2 was 48% higher in incubations with cells from 48-h-old than from 6-h-old piglets. This increase was attributable to a 70% higher O2 consumption by 48-h-old cells. Theoretical O2 consumption rates were computed from the fatty acid flux data and compared with measured O2 consumption. Hepatocytes from SGA and AGA piglets were equally capable of satisfying greater than 75% of their energy needs from fatty acid oxidation. The O2 consumption attributable to 9:0 metabolism was 30% higher than observed for 8:0 and 18:1. All fatty acids apparently spared endogenous fuels to a greater degree in 6-h-old than in 48-h-old piglets.

Animals

Interrelation between Western type cancers and non-Western type cancers as regards their risk variation in time and space. IV. Hormonal transition of Japanese women from the pro-cervical cancer age through the pro-endometrial cancer age to the pro-hypogonadism age.

Chronological trend of urinary steroid excretions in Japanese women was investigated during the period of June 1972 to August 1986 using healthy women of urban and rural origins, patients with breast cancer and patients with either cervical cancer or endometrial cancer. The excretions of 14 neutral steroids were estimated by gas liquid chromatography, and the obtained data were tentatively correlated with the epidemiological backgrounds. In the course of the chronological transition from the 1st stage (1972-1974) to the 2nd stage (1975-79), the urinary steroid pattern of Japanese women with and without cancer experienced a common change to produce specific deviations that were in agreement with the hormonal characteristics of a pill user or of an endometrial cancer patient. At the 3rd stage (1980-86), patients with either cervical cancer or endometrial cancer were distinguished from 1st stage controls by non-specific depression of all androgens, progestins and corticosteroids in urine. Throughout the whole period, both the risk for cervical cancer and the reproductive activity (birth rate) were found to decrease continuously in Japanese women. Evidence was presented to suggest that the above deterioration of the hormonal environment in Japanese women could be related to the stress of modern life rather than to defects in the diet. On the basis of the above findings, the 1st, 2nd and 3rd stages of our investigation were tentatively termed the pro-cervical cancer age, the pro-endometrial cancer age and the pro-hypogonadism age. The relation between the chronological change of urinary steroids and that of the epidemiological background was analyzed from the view point of population ecology.

Age Factors

Aging hypotheses, aging markers and the concept of biological age.

The following two points are made in this article: (1) the likely existence of more than one underlying cause of senescence strengthens the case for the development of a number of reliable markers of aging and (2) the concept of a single biological or functional age for an organism should be used with great caution, if at all.

Aging

Conceptional age, menstrual age, and ultrasound age: a second-trimester comparison of pregnancies of known conception date with pregnancies dated from the last menstrual period.

Ultrasound dating-curve analysis was performed for the biparietal diameter, mean head diameter, and mean trunk diameter in individual singletons, twins, and triplets from in vitro fertilization (IVF) pregnancies and pregnancies with ultrasonographic determination of ovulation. Linear growth was found for all parameters prior to 28 weeks' conceptional age. No differences were observed among singletons, twins, or triplets. Using linear equations, no significant difference was found in systematic errors between pregnancies with a known date of conception and pregnancies dated from the last menstrual period (LMP). Pregnancies with reliable LMPs had only a slight and nonsignificant increase in random errors when compared with pregnancies from IVF. Current polynomial dating equations produced considerable systematic and random errors as well as errors related to fetal growth. Acceptable results were obtained with a new linear equation based on two examinations. We conclude that gestational age based on good menstrual records supported by a pelvic examination in the first trimester may be more reliable than even the best ultrasound method for dating.

Embryonic and Fetal Development