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PubMed2004

Demographics of human supercentenarians and the implications for longevity medicine.

Demographers have forecast that there are going to be a great many more older adults in the next few decades. This will have great implications for longevity medicine. The Gerontology Research Group, affiliated with the UCLA School of Medicine, has compiled and maintained a Table of Worldwide Living Supercentenarians (persons 110 years or older) for the last 4 years, shedding important light on the biological limits of human morbidity and mortality and providing a realistic perspective on the problem of long-term interventions that can reasonably be achieved in the near future.

Aged↗

PubMed2006

Identification of genes involved in healthy aging and longevity.

Studies suggest that the region around microsatellite marker D4S1564 on chromosome 4 is in some way linked to longevity. As a part of the integrated European project Genetics of Healthy Aging (GeHA), we set out to investigate the genes found in this region using a proteomics approach. Here, we report the cloning of six candidate genes.

Aging↗

PubMed2005

Multiple longevity phenotypes and the transition from health to senescence.

Three different longevity phenotypes exist in Drosophila and other model systems, but only two are known in humans. The "missing" phenotype is the delayed onset of senescence phenotype, which can be induced by various interventions, including pharmaceuticals. The lability of the onset of senescence indicates that the mechanisms involved are plastic and can be altered. Only interventions that involve the upregulation of stress resistance genes, probably via the JNK pathway and/or dFOXO3a transcription factor, seem capable of generating a delayed onset of senescence phenotype. The data suggest that the cellular mechanisms responsible for maintaining the cell in a healthy state are under constant attack by ROS and/or abnormal protein accumulation. A stochastic growth factor/signal transduction failure may be the proximal event responsible for the decreased efficiency of the cell's defenses, resulting in the onset of senescence, degradation of the gene interaction network, and continuing loss of function.

Aging↗

PubMed2003

Reduced longevity in untreated patients with isolated growth hormone deficiency.

Increased longevity of hypopituitary dwarf mice and GH- resistant knockout mice appears to be in contrast with observations made in clinical practice. In humans, on one hand hypopituitarism and GH deficiency (GHD) are believed to constitute risk factors for cardiovascular disease and, therefore, early death. But on the other hand, patients with a PROP-1 gene mutation, presenting with a combined pituitary-derived hormonal deficiency, can survive to a very advanced age, apparently longer than normal individuals in the same population. The aim of this study was to analyze the impact of untreated GHD on life span. Hereditary dwarfism was recognized in 11 subjects. Genetic analysis revealed an underlying 6.7-kb spanning deletion of genomic DNA encompassing the GH-1 gene causing isolated GHD. These patients (five males and six females) were never treated for their hormonal deficiency and thus provide a unique opportunity to compare their life span and cause of death directly with their unaffected brothers and sisters (11 males and 14 females) as well as with the normal population (100 males and females). Although the cause of death did not vary between the two groups, median life span in the GH-deficient group was significantly shorter than that of unaffected brothers and sisters [males, 56 vs. 75 yr (P < 0.0001); females, 46 vs. 80 yr (P < 0.0001)]. Therefore, with the wealth of information regarding the beneficial effects of GH replacement and the dramatic findings of this study, GH treatment in adult patients suffering from either childhood- or adult-onset GHD is crucially important.

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PubMed1995

Tremor and longevity in relatives of patients with Parkinson's disease, essential tremor, and control subjects.

To study the relation between essential tremor (ET) and Parkinson's disease (PD), we compared the frequency of familial tremor in relatives of patients with PD (N = 391), ET (N = 140), and the combination of ET and PD (N = 125) with the frequency in patients with progressive supranuclear palsy (PSP) (N = 99) and normal age-matched controls (N = 104). Tremor was present in 96 (5.1%) of 1,874 parents and siblings of patients with PD, 152 of 650 (23.4%) relatives of patients with ET, 91 (20.7%) of 439 relatives of patients with ET-PD, 12 of 462 (2.6%) relatives of patients with PSP, and 10 of 448 (2.2%) relatives of normal controls. The high frequency of familial tremor among relatives of patients with PD, and especially those with the ET-PD combination, compared with relatives of patients with PSP or of normal controls suggests that there is an association of PD and familial tremor. Since the most common form of familial tremor is ET, our study provides support for the notion that ET and PD are pathogenetically related. We also found that parents with tremor lived on the average 9.2 years longer than those without tremor. The association of familial tremor with significantly increased longevity suggests that familial tremor confers some anti-aging influence. Alternatively, tremor may be a simple byproduct of the aging process.

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PubMed1996

Aged garlic extract prolongs longevity and improves spatial memory deficit in senescence-accelerated mouse.

The effects of aged garlic extract (AGE), chronically administered in the diet, on longevity and spatial learning performances were studied using the senescence-accelerated mouse (SAM). A solid diet containing 2% AGE was given to senescence-accelerated-prone mouse 8 (SAMP8) and senescence-accelerated-resistant mouse 1 (SAMR1) from 2 months of age. The survival ratio of SAMP8, a substrain of senescence-accelerated-prone mouse, was significantly lower than that of SAMR1, a substrain of senescence-resistant mouse. In the SAMP8, administration of AGE perfectly prevented the decrease in survival ratio. Moreover, AGE markedly improved the learning deficits of SAMP8 in the Morris water maze test. These results suggest the possibility that AGE prevents physiological aging and age-related memory disorders in human.

Aging↗

PubMed1982

Growth and longevity of rats fed an agar-bound diet.

A conventional diet fed to rats in an agar-gel base reduced mature bodyweight by about 25% and increased longevity when compared to the same diet in pelleted form. Dry matter intake was not affected, but food utilization was considerably poorer. The use of a diet in agar gel may, therefore, provide an improved toxicological assay, especially when used in combination with flushing racks housing 2 animals per cage, where exposure of the animal technician to dust was reduced.

Agar↗

PubMed1995

[Relationships among obesity, atherosclerotic disorders, and longevity in the elderly. An autopsy study].

To evaluate the effect of obesity on atherosclerosis, health, and longevity in the elderly, we studied the relationship between body mass index, atherosclerosis, and the duration of disability by multivariate analyses. We analyzed data from 521 residents of the Yokufu-kai home for the aged. They underwent a 50 g oral glucose tolerance test, and autopsies were done after they died. All functional evaluations were done retrospectively from the hospital records. The mean age of the time of death was significantly higher in the overweight group than in the lean group. The incidence of marked cerebral atherosclerosis was significantly higher in the overweight and the obese groups than in the lean and the medium-weight groups. The incidence of cerebral infarction with neurological deficits was significantly higher in the overweight group than in the lean group, but there were no differences in other types of infarction. The incidence of severe coronary artery stenosis was significantly higher in the obese group than in the lean and medium-weight groups, but there was no difference in the incidence of myocardial infarction between groups. There were no differences in the incidence of severe atherosclerosis of the aorta, femoral artery, or renal artery between groups. Patients in the overweight group were bedridden for a significantly longer time than those in the lean group. We conclude that body weight in the elderly is positively associated with survival. However, overweight subjects suffered from non-fatal cerebral infarction, and prolonged survival was associated with greater disability.

Activities of Daily Living↗

PubMed2004

The GH/IGF-I axis and longevity.

Several converging lines of evidence obtained over the last years in a wide variety of experimental model organisms suggest that the ageing process is regulated by genes that encode proteins from the somatotroph axis: longevity genes like daf-2, which were identified using mutant Caenorhabditis elegans strains, turned out to be orthologues of the mammalian genes encoding insulin-like signalling cascade proteins. Transgenic flies with mutations in the corresponding insect genes showed a similar pattern of increased lifespan. Finally, mice with spontaneous mutations leading to pituitary hormone deficiency significantly outlived controls. While these and other genetic models suggest that the downregulation of the somatotroph axis can slow the ageing process, other results from studies using pharmacological administration of growth hormone suggest that such stimulating treatment can restore some of the phenotypic traits associated with youth. To better understand the role of the insulin-like receptors in mammalian lifespan regulation and ageing, we explored the phenotype of heterozygous IGF-I receptor (IGF1R) knockout mice. Compared with control littermates these mutants live longer without any obvious impairment of their health and physiology, except a reduced glucose tolerance that we observed in males. These IGF1R(+/-) mutants were also more resistant to oxidative stress in vivo, and we identified a possible molecular pathway linking underphosphorylation of IGF-I receptors to the lack of activation of p66Shc, a protein capable of increasing resistance to oxidative stress through regulation of a set of downstream genes. These and other results suggest that in mammals too, lifespan can be increased by continuous, long-term downregulation of IGF signalling. Since growth hormone administration normally stimulates IGF production in tissues, the question arises whether the beneficial effects of GH, as reported by others, could be IGF independent. This hypothesis can be addressed, for example, by adequately combining existing transgenic mouse models.

Aging↗

PubMed1991

Effects of germfree status and food restriction on longevity and growth of mice.

An investigation was undertaken to study the effects of germfree (GF) status and mild food restriction on life span in GF and specific pathogen-free (SPF) male ICR mice either full-fed (ad libitum) or on a restricted diet of 4.5 grams per day (equivalent to approximately 80% of full-fed intake) from five-week-old. The mean life span of the full-fed SPF and GF mice was 75.9 and 88.9 weeks respectively, while the mean life span of the food-restricted SPF and GF mice was 117.5 and 109.6 weeks, respectively. Mice in both GF and SPF food-restricted groups were characterized by lower body weight and increased survival. These findings suggest that the cessation of growth may be importantly and perhaps causally related to longevity. The GF mice survived longer than the SPF mice, but the combination of GF status with food restriction did not seem to extend life span more than food restriction alone.

Aging↗

PubMedDate not supplied

The influence of sugars and amino acids on the blood-feeding behaviour, oviposition and longevity of laboratory colony of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae, Phlebotominae).

Schneider's Drosophila medium, a complex amino acid rich medium was tested alone and with seven different sugars for some aspects of the biology of Lutzomyia longipalpis. Statistically significant results were obtained when sucrose was used alone, indicating that among the sugars tested, this is still the most suitable and practical one for the maintenance of L. longipalpis colonies. However, the addition of Schneider's medium to a pool of different sugars, was suggested to be related with the acceptance of the first and second blood meals and to longevity, these being, obviously, quite relevant aspects when transmission experiments are contemplated.

Amino Acids↗

PubMed2006

Reproductive parameters and longevity of Gryon gallardoi (Brethes) (Hymenoptera: Scelionidae) parasitizing Spartocera dentiventris (Berg) (Hemiptera: Coreidae) eggs.

The fecundity, daily progeny and longevity of Gryon gallardoi (Brethes) (Hym.; Scelionidae) were determined under laboratory conditions, using Spartocera dentiventris (Berg) (Hem.; Coreidae) eggs as host. Nineteen G. gallardoi females and 34 males were reared at 25 +/- 1 degrees C, with a 12 h photophase, fed on a 10% aqueous honey solution and provided with 25-30 S. dentiventris eggs daily. The average pre-oviposition period was 1.3 +/- 0.35 days, although some females began laying from the day of emergence. On average, oviposition lasted for 10.1 +/- 1.74 days, reaching a peak on the second day, with 67.5 +/- 11.29 eggs laid. The post-oviposition period was short (2.4 +/- 0.48 days). G. gallardoi females lived significantly longer than males: 13.7 +/- 1.94 and 10.6 +/- 1.78 days, respectively. The overall sex ratio was 0.79. The results reported here on the reproductive capability of the species suggest it may have a good potential as an agent for the control of S. dentiventris.

Animals↗

PubMed2002

Development, survival, body weight, longevity, and reproductive potential of Oemena hirta (Coleoptera: Cerambycidae) under different rearing conditions.

Oemona hirta (F.) is a New Zealand native longicorn beetle, whose larvae bore into the wood of branches and stems of living trees and vines, causing serious damage. To explore effective methods for maintaining laboratory colonies and biology of immature stages of this species we evaluated four laboratory rearing methods with both natural and artificial diets and compared biological parameters of laboratory colonies with those of field-collected insects. On an artificial diet, approximately 40% of neonate and 70% of autumn- and 11% of winter-collected larvae reached adulthood. Neonate larvae could not complete their development in cut poplar (Populus nigra variety italica Koehne) twigs; however, when twigs were standing in water >46% of neonate larvae survived to adulthood. Mean larval development time ranged from approximately150 to almost 300 d, depending on rearing methods. Mean pupal stage ranged from 15 to 19 d. Adult females were significantly heavier than males. Although adult females from field-collected twigs and reared on the artificial diet had similar mean body weight, which was significantly greater than that of other rearing colonies, the potential fecundity was the highest in the former (83.1 +/- 29.4 eggs) and the lowest in the latter (33.5 +/- 9.1 eggs). In all laboratory-reared and field-collected insects, the total number of eggs produced (eggs laid + eggs that remained in dead female body) by females was positively correlated with their body weight. When larvae fed on the artificial diet, there was no positive correlation between the number of eggs successfully laid and female body weight. However, when larvae lived on natural food, a positive correlation was found. In laboratory colonies, mean longevity of females (36 to 52 d) was slightly greater than that of males (30 to 50 d) without significant difference between sexes but in the adults from field-collected twigs, males (52 d) lived significantly longer than females (33 d). In terms of time, labor, and the number of resulting adults, collecting larvae in the field in autumn and then transferring them onto artificial diet is the most effective method for maintaining a laboratory colony.

Animals↗

PubMed2003

Effect of osmotic desiccation on longevity and temperature tolerance of Phasmarhabditis hermaphrodita (Nematoda: Rhabditidae).

Limited storage stability severely restricts the biological control potential of slug-parasitic nematodes. In a series of experiments, we evaluated the effects of temperature and osmotic desiccation on the short- and long-term survival of the slug-parasitic nematode Phasmarhabditis hermaphrodita. Nematode survival in petri dishes at 1,500 infective juveniles/ml did not differ significantly at 5, 10, and 15 C but declined rapidly at 25 and 30 C. At 25 C about 50% of the nematodes survived for 4 wk, but at 30 C no nematode survived past 1 day. About 50% of the nematodes survived for 32 wk at 20 C. About 35-40% of the nematodes survived up to a year at 5, 10, and 15 C. Phasmarhabditis hermaphrodita showed poor survival under osmotic desiccation in glycerol with 15 and 20% glycerol significantly reducing survival at 5 and 15 C. Although the nematodes tolerated 10% glycerol, this level of desiccation also did not enhance long-term survival at either 5 or 15 C. There was a significant decrease in nematode survival in 10% glycerol at 25 C during the first 2-3 wk, but about 16% of the nematodes survived for 6 wk in 10% glycerol as compared with only 1% survival in water. The greatest benefit of osmotic desiccation in glycerol was observed in the enhanced survival of P. hermaphrodita at temperature extremes. Over 96% of the nematodes survived a 6-hr exposure to 35 C in 10% glycerol, whereas only 9% survived in water. Similarly, over 90% of the nematodes survived an exposure to -20 C for 4 hr in 10% glycerol, but less then 2% survived in water. We conclude that 5-15 C is an optimum temperature range for the storage of P. hermaphrodita. We also conclude that osmotic desiccation in 10% glycerol can substantially increase survival of P. hermaphrodita at temperature extremes (35 and -20 C) for short periods but has no effect on nematode longevity at the optimum temperature range of 5-15 C.

Animals↗

PubMed2002

Benefits of smoking cessation for longevity.

OBJECTIVES: This study determined the life extension obtained from stopping smoking at various ages. METHODS: We estimated the relation between smoking and mortality among 877,243 respondents to the Cancer Prevention Study II. These estimates were applied to the 1990 US census population to examine the longevity benefits of smoking cessation. RESULTS: Life expectancy among smokers who quit at age 35 exceeded that of continuing smokers by 6.9 to 8.5 years for men and 6.1 to 7.7 years for women. Smokers who quit at younger ages realized greater life extensions. However, even those who quit much later in life gained some benefits: among smokers who quit at age 65 years, men gained 1.4 to 2.0 years of life, and women gained 2.7 to 3.7 years. CONCLUSIONS: Stopping smoking as early as possible is important, but cessation at any age provides meaningful life extensions.

Adult↗

PubMed2005

Role of oxidative and nitrosative stress, longevity genes and poly(ADP-ribose) polymerase in cardiovascular dysfunction associated with aging.

Epidemiological studies demonstrated that even in the absence of other risk factors (e.g. diabetes, hypertension, hypercholesterolemia), advanced age itself significantly increases cardiovascular morbidity. Although aging is inevitable, cardiovascular gerontologists recognize that a better understanding of the aging process in the not-so-distant future will lead to pharmacological interventions that considerably delay the functional decline of the cardiovascular system. Since the original publishing of the free radical theory of aging, an increased production of reactive oxygen species has been implicated both in the aging process and the development of age-related cardiovascular diseases. This review focuses on the role of oxidative and nitrosative stress in cardiovascular dysfunction in aging, downstream mechanisms including activation of NF- kappaB, and the role of poly(ADP-ribose)polymerase (PARP) and longevity genes that are linked to regulation of cellular redox status and oxidative stress resistance (p66(shc), sirtuins, FOXO transcription factors).

Aging↗

PubMed2000

A new comprehensive study on aging--the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA).

A new comprehensive longitudinal study of aging, the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA) started in November 1997. The participants of this study will be 2,400 residents aged 40 to 79 years who were age- and gender-stratified random samples selected from the NILS area. All participants provided written informed consent after a detailed explanation of the study. They will be examined at the NILS-LSA Examination Center every two years. Their first wave examinations will be finished by the end of March 2000. The examined variables number over 1,000, including clinical evaluations, medical examinations, anthropometry, body composition, physical functions, physical activities, psychological assessments, nutritional analysis and molecular epidemiology. By the end of September 1999, 1,643 men and women had completed their first wave examinations.

Adult↗

PubMed1993

The fallacy of the argument for reduced longevity in left-handers.

The fallacy of the argument for reduced longevity in left-handers depends on the use of the writing hand in the assessment of the present generation of elderly people, when writing was not used as a criterion in the early years of the century. A 'thought' experiment demonstrates that a sample of left-handers is likely to be younger than a sample of right-handers alive in the population and this would be true also of the recently deceased.

Adult↗