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PubMed1983

Energy metabolism, brain size and longevity in mammals.

The mathematical relations between basal energy metabolism, brain size, and life span in mammals have been investigated. The evolutionary level of brain development, or encephalization (c), is a function both of brain weight (E) and of body weight (P) according to (formula; see text) Brain weight was found to be a linear function of the product of encephalization and basal metabolic rate. The oxygen consumption of the brain (Mbrain) is proportional to both encephalization and body weight according to (formula; see text) The ratio of metabolic rate in the cerebral cortex to that in the brain as a whole depends solely upon the degree of encephalization and is independent of the size of the animal. The maximum potential life span of a mammal was found to be proportional to the product of its degree of encephalization and the reciprocal of its metabolic rate per unit weight. Life span may be regarded as the algebraic sum of two components: (1) a deduced somatic component (Lb) inversely related to the basal metabolic rate per unit weight, and (2) an encephalization component (Le) related directly to the evolutionary increase of relative brain size.

Animals↗
PubMedDate not supplied

Redox regulation of heat shock protein expression by signaling involving nitric oxide and carbon monoxide: relevance to brain aging, neurodegenerative disorders, and longevity.

Increased free radical generation and decreased efficiency of the reparative/degradative mechanisms both primarily contribute to age-related elevation in the level of oxidative stress and brain damage. Excess formation of reactive oxygen and nitrogen species can cause proteasomal dysfunction and protein overloading. The major neurodegenerative diseases are all associated with the presence of abnormal proteins. Different integrated responses exist in the brain to detect oxidative stress which is controlled by several genes termed vitagenes, including the heat shock protein (HSP) system. Of the various HSPs, heme oxygenase-I (HO-1), by generating the vasoactive molecule carbon monoxide and the potent antioxidant bilirubin, could represent a protective system potentially active against brain oxidative injury. The HO-1 gene is redox regulated and its expression is modulated by redox active compounds, including nutritional antioxidants. Given the broad cytoprotective properties of the heat shock response, there is now strong interest in discovering and developing pharmacological agents capable of inducing the heat shock response. These findings have opened up new neuroprotective strategies, as molecules inducing this defense mechanism can be a therapeutic target to minimize the deleterious consequences associated with accumulation of conformationally aberrant proteins to oxidative stress, such as in neurodegenerative disorders and brain aging, with resulting prolongation of a healthy life span.

Aging↗
PubMed2006

Embryonic myocardium shows increased longevity as a functional tissue when cultured in the presence of a noncardiac tissue layer.

A major aim of regenerative medicine is the construction of bioengineered organs and tissue for transplantation into human patients; yet living tissue is dynamic, and thus arranging cellular and extracellular constituents into an architecture resembling normal adult organs may not be sufficient to maintain tissue stability. In this study, we used cultures of embryonic chick heart tissue as a model to explore how newly formed cardiac tissue constructs can sustain their morphological structure and functional capabilities over extended periods. During the initial days of incubation, embryonic cardiac explants will thrive as beating three-dimensional tissue aggregates. However, within the first week of culture, cardiac aggregates lose their contractile function and flatten. After 2 weeks of incubation, the cardiac cells will have spread out into a homogeneous monolayer and dedifferentiated to a noncardiac phenotype. In contrast, when the embryonic heart tissue was co-cultured with a noncardiac cell layer obtained from adult bone marrow, the cardiac aggregates maintained their contractile function, three-dimensional tissue morphology, and myocyte phenotype for a full month of incubation. The capacity of this noncardiac cell layer to sustain the phenotype and morphology of the cardiac explants was partially replicated by treatment of the heart tissue with conditioned media from bone marrow cells. These findings are discussed in regard to the importance of adjacent cell layers for facilitating organogenesis in the developing embryo and having potential utility in producing stable bioengineered tissue constructs.

Animals↗
PubMed1990

High-density lipoprotein cholesterol and longevity.

Serum total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides were studied in three groups: (1) 85 healthy subjects aged 85-89 years, (2) 62 patients without coronary artery disease aged 38-62 years, and (3) 323 patients aged 32-69 years with triple-vessel disease diagnosed by coronary angiography. The mean values for total cholesterol were significantly higher in patients with triple-vessel disease than in those without coronary artery disease and in the elderly. Total cholesterol was over 6.5 mmol/l in 32% of the elderly, in 31% of patients without coronary artery disease and in 42% of patients with triple-vessel disease, but these differences were not significant. HDL-cholesterol and the ratio of HDL/total cholesterol were significantly higher in the elderly than in the patients without coronary artery disease and patients with triple-vessel disease. Serum HDL-cholesterol was over 1.0 mmol/l in 92% of the elderly, in 69% of patients without coronary artery disease and in 46% of patients with triple-vessel disease, the differences being significant between all groups.

Adult↗
PubMed1998

Quality of life and longevity: a study of centenarians.

OBJECTIVE: Interest in centenarians has focused on two particular aspects: the antecedents of extreme old age and the psychophysical well-being of the very old. Our study deals with the latter aspect and aims to assess the quality of life of Italian centenarians. METHOD: Using data collected using two questionnaires designed to investigate quality of life in elderly people, three groups of 38 elderly subjects were compared: centenarians and subjects aged between 75 and 85 years and 86 and 99 years. RESULTS: The centenarians complained less spontaneously about their health (maintained in part by medical treatments), but declared having greater functional disability. Their cognitive function appears to be reasonably well preserved and they have lower scores for anxiety and depression than the subjects in the two younger groups. They consider themselves religious, satisfied with their financial situation but no longer interested in sex or involved in recreational activities. They report greater satisfaction with life and with social and family relations than do less elderly individuals. CONCLUSIONS: The centenarians we interviewed seem to be well adapted to their lives and to maintain a more positive attitude than the subjects in the two younger groups.

Adaptation, Psychological↗
PubMed1992

Traits that influence longevity in mice: a second look.

Analysis of genetic interactions in the F2 of an intercross of (C57BL/6 x DBA/2) F1J revealed influences of genetic factors on life span. Females lived longer than males. Dilute brown females died sooner than females of other colors. H-2b/H-2b males died sooner than H-2b/H-2d or H-2d/H-2d males, except that among dilute brown males those of typeH-2b/H-2d died sooner. Cluster analysis suggested that male and female genotypes each fall into two groups, with female dilute brown mice having shorter lives than other females, and male H-2b/H-2b mice except dilute brown and dilute brown H-2b/H-2d mice having shorter lives than other males. The association of heterozygosity with life span was clearer in females than in males, yet the longest-lived female genotype was homozygous H-2d/H-2d, of dominant Black phenotype at the Brown locus of chromosome 4, and homozygous dd at the Dilute locus of chromosome 9. The shortest-lived females were dilute brown H-2b/H-2b. The longest-lived and shortest-lived male genotypes were dilute brown H-2d/H-2d and dilute brown H-2b/H-2d, respectively. Although histological findings at postmortem differed between the sexes, there was no association of particular disorders with other genetic markers. The importance of H-2 in males was confirmed, but the allelic effects were perturbed, possibly by the absence of Sendai infection in this experiment. Overall our studies suggest that genetic influences on life span involve interactions between loci, and allelic interactions may change with viral infections or other environmental factors.

Animals↗
PubMed1993

Longevity-determining genes in Caenorhabditis elegans: chromosomal mapping of multiple noninteractive loci.

We have used chromosome mapping with polymorphic markers to define genetic components governing life span in the nematode Caenorhabditis elegans. A complex recombinant-inbred population was derived from an interstrain cross, yielding > 1000 genotypes, each a composite of homozygous segments from the two parental strains. Genotypes were analyzed for the last-surviving 1-5% of worms in aging cohorts, and for young controls, by multiplex polymerase chain reaction using polymorphic markers to distinguish the parental alleles. We identified five regions of the genome at which one parental allele was significantly enriched in long-lived subpopulations. At four of five loci, the same alleles were selected in aging cohorts maintained under two different conditions, implying that these genes determine life span in differing environments.

Animals↗