Physiological assays for biological age in mice: Relationship of collagen,renal function,and longevity

Tests of physiological changes with age are illustrated by collagen denaturation times of tail tendon fibers, and urine concentrating abilities; the tests are evaluated using the following four criteria: change with age, repeatability, relationship to other assays, and relationship to longevity. These tests usually showed highly significant changes with age when mice of different ages were compared for nine mouse genotypes, however neither appeared to be related to subsequent longevities of individual mice. When average values for eleven mouse genotypes were compared, the mean longevities of the genotypes were not significantly correlated with their mean collagen denaturation times or mean renal concentrating abilities, tested at two different ages. The relationships between all three factors—collagen denaturation times, urine concentrating abilities, and longevities—were tested in the same individuals for mice of six different genotypes at 600–700 days of age. Only one marginally significant correlation appeared out of 21 tested; this probably occurred by chance. We conclude that tail tendon collagen denaturation times and urine concentrating abilities change with age independently of each other; furthermore, these changes are unrelated to subsequent longevities, at least when linear relationships are tested. These data suggest that aging is timed by more than one mechanism and demonstrate that strong correlations with chronological age do not necessarily indicate that independent tests will be correlated with longevity or with each other.     

Oral health for achieving longevity

Oral frailty is defined as a decrease in oral function accompanied by a decrease in mental and physical functions. Studies showing that people with oral frailty are at high risk of physical frailty, sarcopenia, severe conditions requiring nursing care and death have been reported in Japan. An increase in life expectancy and maintenance of teeth result in a decrease in the effect of the number of teeth. In contrast, a decrease in oral function as a result of aging has been suggested to have major effects on dysfunction and mortality risk. The present report is a narrative review of major clinical studies on the relationships of the number of teeth, dentures, occlusion and oral function with longevity, with the aim of providing information for future studies centered on oral function in Japan or overseas. This review clearly shows the relationships of the number of teeth, dentures, and occlusion with health and longevity. Recent studies have shown that, besides maintenance of the number of teeth, attempting to maintain or increase oral function, having a good diet and maintaining nutritional status are all linked to general health. Decreased oral function is a major risk factor for developing malnutrition and sarcopenia. Oral frailty, a new concept that has been recently introduced in Japan, is considered to have major effects on dental and oral health policies in Japan, in the old‐age group, and is expected to be reflected in the dental and oral health policies of various countries, as they also predict increased life expectancies. Geriatr Gerontol Int 2020; ??: ??–?? .     

HDL: a recipe for longevity

The concentration of high density lipoprotein cholesterol (HDL-C) has been found to be a powerful negative predictor of premature coronary heart disease (CHD) and stroke in human prospective population studies. Evidence of the protective properties of HDLs has also been documented in the elderly and their offspring. HDLs mediate several functions that provide an insight into their potential anti-atherogenic mechanisms. Intervention strategies to prevent CHD have generally focused on lowering low-density lipoprotein cholesterol (LDL-C). However, several lifestyle and pharmacological interventions have the capacity to raise the level of HDL-C. As data accumulate on the protective role of HDLs, there is growing support for interventions that act to raise HDL-C concentrations.     

A new field record for bat longevity

A new longevity record has been established for a free-living bat-41 years for a male Brandt's bat, Myotis brandtii. The exceptional longevity of bats generally, and this species in particular, should make bats of special interest for researchers studying mechanisms of slow aging.     

Genetics of longevity

—Recent studies on the genetics of aging in the yeast Saccharomyces cerevisiae, the roundworm Caenorhabditis elegans, and the fruit fly Drosophila melanogaster have converged revealing the central role of metabolic capacity and resistance to stress in determining life span. Signal transduction has emerged from these studies as an important molecular mechanism underlying longevity. In their broad features, the results obtained in these genetic models are applicable to the dietary restriction paradigm in mammals, suggesting a general significance. It will be of interest to determine whether many of the molecular details will also pertain. The examination of centenarian populations for the frequency of certain alleles of pertinent genes may provide insights into the relevance of the conclusions of studies in invertebrates to human aging. These population genetic studies can be augmented by mechanistic studies in transgenic mice.     

Exceptional familial clustering for extreme longevity in humans

Four families highly clustered for extreme longevity are described here, representing the first report of clustering for this phenotype. Families such as these may prove to be helpful in the further understanding of the genetic contribution to achieving exceptional longevity.     

Multiple-stress analysis for isolation of Drosophila longevity genes

Long-lived organisms tend to be more resistant to various forms of environmental stress. An example is the Drosophila longevity mutant, methuselah, which has enhanced resistance to heat, oxidants, and starvation. To identify genes regulated by these three stresses, we made a cDNA library for each by subtraction of "unstressed" from "stressed" cDNA and used DNA hybridization to identify genes that are regulated by all three. This screen indeed identified 13 genes, some already known to be involved in longevity, plus candidate genes. Two of these, hsp26 and hsp27, were chosen to test for their effects on lifespan by generating transgenic lines and by using the upstream activating sequence/GAL4 system. Overexpression of either hsp26 or hsp27 extended the mean lifespan by 30%, and the flies also displayed increased stress resistance. The results demonstrate that multiple-stress screening can be used to identify new longevity genes.     

Why calorie restriction would work for human longevity

Experimentally imposed calorie restriction (CR) is shown to result in the most reproducible endpoint of lifespan extension in all animals models tested. In this presentation, the question of CR’s effect on human longevity is reviewed by discussing data pertinent to the putative efficacy of CR on humans. Arguments are presented in support of this possibility based on CR’s unique abilities to retard biological functional declines and to deter pathological processes, both of which are major targets of deleterious oxidative stress. To delineate the cellular and molecular mechanisms of CR’s efficacy on human longevity, this review elaborates on the modulation of CR on the inflammatory process, a common risk factor for many chronic diseases. Discussions also include evidence from human data on the effect of CR in the loss of body weight, known to suppress inflammatory cytokines, subsequently leading to the reduction of chronic diseases known to compromise the functional longevity of humans.     

Female fertility and longevity

Does bearing children shorten a woman’s life expectancy? Pleiotropic theories of aging predict that it should, and in particular, the Disposable Soma theory predicts unequivocally that this effect should be inescapable. But many demographic studies, historic and current, have found no such effect. In this context, the Caerphilly cohort study stands apart as the sole test that corroborates the theory. Why has this study found an effect that others fail to see? Their analysis is based on Poisson regression, a statistical technique that is accurate only if the underlying data are Poisson-distributed. But the distribution of the number of children born to women in the Caerphilly database departs strongly from Poisson at the high end. This makes the result overly sensitive to a handful of women with 15 children or more who lived before 1700. When these five women are removed from a database of more than 2,900, the Poisson regression no longer shows a significant result. Bilinear regression relating life span to fertility and date of birth results in a small positive coefficient for fertility, in agreement with the main trend of reported results.     

The symmetry of longevity

We tested the hypothesis that relatively symmetrical flies live longer. Vein measurements on the left and right wings from the same individual were used to characterize bilateral symmetry in relationship to age-specific survival in defined cohorts. A longitudinal cohort study supported the hypothesis of a correlation between bilateral symmetry and longevity. For another type of experiment, wings were removed from females and males at approximately the beginning of adult life. Thus, there would be no effect of wings per se on adult survival. These wings were measured to characterize bilateral asymmetry, and the day of death of each dewinged individual was determined. Wing symmetry of females and males proved to be a statistically significant predictor of life span, especially for males.