Mammalian growth and development parameters, cell proliferation in culture and the maximal life span]

The maximum life span of mammals is known to be proportional to the pregnancy duration and to the age at puberty. We found that the maximum life span of mammals was also proportional to the number of cell doublings, and inversely proportional to the rate of duplication of these cells, during embryogenesis or for the time from zygote formation to growth termination. We found also that the life span of "stationary phase aging" transformed Chinese hamster cells (time from subcultivation until culture "death", i.e., until the moment when the number of live cells is less than 10% of their number at saturation density) was proportional to the duration of their growth and number of cell doublings during the period from subcultivation to saturation density, and inversely proportional to the rate of cell culture duplication during the same period. The dependencies for cell cultures and mammals proved to be analogous to each other. An approximately twofold decrease in the cell duplication rate, as a result of a decrease of the growth medium temperature from 37 to 27 degrees C or the introduction of ethanol to a final concentration 2%, increased the life span of "stationary phase aging" cultures more than twofold. The data obtained suggest that influences resulting in optimized delay of the rate of cell duplication, and correspondingly the mean rate of proliferation during the period of growth in mammals, may increase their maximum life span.     

Analysis of correlation between some parameters depending on cell proliferation and life span of "stationary phase aging" cultures and maximum life span of mammals

Earlier we developed a "stationary phase aging" model and introduced a definition of life span of "stationary phase aging" cell cultures. In this model the cells grow after seeding in flasks without subcultivation and medium change. They reach cell saturation density, stop dividing, gradually degrade ("stationary phase aging") and perish. By the term "culture life span" we designate the time from cell seeding until culture death. We designate the culture as dead when the number of living cells is less than 10 per cent of their number at saturation density of cell culture. The life span of transformed Chinese hamster cells was found to be proportional to the duration of their growth from cell seeding up to saturation density, as well as to the number of cell culture doublings and to be inversely proportional to the velocity of cell culture doubling for the same growth period. Maximum life span of mammals is known to be proportional to pregnancy duration and to the age at puberty. We found that maximal life span of mammals was proportional to the number of cell population doublings and inversely proportional to the velocity of cell population doubling during embryonal period or for the time from zygote to growth termination. The dependences for cell cultures and for mammals are analogous to each other.     

Sexual Conflict,Life Span,and Aging

The potential for sexual conflict to influence the evolution of life span and aging has been recognized for more than a decade, and recent work also suggests that variation in life span and aging can influence sexually antagonistic coevolution. However, empirical exploration of these ideas is only beginning. Here, we provide an overview of the ideas and evidence linking inter- and intralocus sexual conflicts with life span and aging. We aim to clarify the conceptual basis of this research program, examine the current state of knowledge, and suggest key questions for further investigation.Sexual conflict arises because the sexes maximize their fitness via different, and often mutually incompatible, strategies, and its signature has been detected across a wide range of morphological, physiological, behavioral, and life-history traits in many species. A number of investigators have suggested that sexual conflict could play an important role in the evolution of two particularly interesting life-history traits: life span and aging (Svensson and Sheldon 1998; Promislow 2003; Bonduriansky et al. 2008; Maklakov and Lummaa 2013). Sexual conflict can affect life span and aging rate at both proximate (within-generation) and ultimate (evolutionary) scales. Sexually antagonistic behavioral or physiological interactions that increase mortality rate in one or both sexes (interlocus sexual conflict) could drive the evolution of faster life histories. Moreover, sex-specific optimization of reproductive strategies may often result in sex differences in life span and aging rates, and sexually antagonistic selection on shared genetic architecture can displace one or both sexes from their sex-specific optima for these traits (intralocus sexual conflict). Conversely, a change in life histories because of environmental fluctuations could affect the degree of sexual conflict in a population and influence sexual coevolution. Although evidence for sexual conflict is rapidly accumulating, our understanding of its relationship to life span and aging remains rudimentary. In this review, we provide a critical review of recent literature and highlight areas that require further investigation.     

Comparison of leaf life span, photosynthesis and defensive traits across seven species of deciduous broad-leaf tree seedlings

BACKGROUND AND AIMS: Leaf life span, photosynthetic parameters and defensive traits were compared across seven species of deciduous broad-leaved tree seedlings native to northern Japan to test the "cost-benefit hypothesis" that more productive leaves are more susceptible to herbivore attack than less productive leaves. METHODS: Studies were made on three early successional species, Alnus hirsuta, Betula maximowicziana and Betula platyphylla "japonica"; one mid-successional species, Ostrya japonica, and three late-successional species, Carpinus cordata, Quercus mongolica 'grosseserrata' and Acer mono. Photosynthetic parameters and defensive traits (total phenolics, condensed tannin and toughness) of leaves were measured for each species, and a bioassay test with Eri silkmoth larvae (Samia cynthia ricini) was undertaken to evaluate differences between species in susceptibility to herbivore attack. KEY RESULTS: Early successional species have a shorter leaf life span (62-88 d) than late successional species (155-187 d). Leaf nitrogen content and light-saturated photosynthetic rate per unit leaf area (P(sat)-area) and per unit leaf mass (P(sat)-mass) were negatively correlated with leaf life span. The nitrogen content of early successional species was about 30 mg g(-1) and that of late successional species was about 16 mg g(-1). Leaf toughness and the C/N ratio were positively correlated with leaf life span, although condensed tannin was not correlated with leaf life span. The bioassay test showed that the number of days the larvae survived was negatively correlated with leaf life span. Average survival of larvae feeding on leaves of A. hirsuta, which has the shortest leaf life span, was 14.4 d and that of Q. mongolica, which has the longest leaf life span, was 6.6 d. The number of days of larval survival was positively correlated with leaf nitrogen content. There was no correlation between days of larval survival and defensive traits. CONCLUSIONS: These results indicate that species with a shorter leaf life span have higher photosynthetic productivity and are more susceptible to herbivore attack than species with a longer leaf life span. This supports the "cost-benefit hypothesis".     

Lipid peroxidation and the life span of Drosophila melanogaster

Studies have been made on the relationship between incubation temperature (20-30 degrees C) of D. melanogaster and the life span as well as the content of various products of lipid peroxidation. It was shown that the increase in the environmental temperature results in the decrease in the life span, the content of unsaturated fatty acids and conjugated hydroxyperoxids; ketodienic content increases. Strong correlation was observed between the life span and the content of peroxidation products. As it is indicated by coefficients of bifactorial linear regression with interaction, conjugated hydroperoxids and ketodiens exert negative influence on the life span. Their combined effect on the life span is less significant than the sum of their separate effects, which indicates the existence of common "canals" of their influences on the life span.     

Evolutionary analysis of life span, competition, and adaptive radiation, motivated by the Pacific rockfishes (Sebastes)

The Pacific rockfishes (Sebastes spp) are remarkable for both their diversity (on the order of 100 species) and range of maximum life span ( approximately 10 years for Calico rockfish to approximately 200 years for Rougheye rockfish). We describe the natural history and patterns of diversity and life span in these species and then use independent contrasts to explore correlates of these. When phylogenetic history is taken into account, maximum life span is explained by age at maturity, size at maturity, and the interaction of these two. We introduce a life-history model that allows insight into the origin of these correlations. We then describe a variety of mechanisms that may increase lifepans and diversity. These include fluctuating environments (in which organisms basically have to "wait out" bad periods to reproduce successfully), diversity, and longevity inspired by interspecific competition and physiological complexity in growth and accumulation of cellular damage. All of the results point toward the importance of flat or "indifferent" fitness surfaces as a key element in the evolution of diversity. We conclude that further development of the theory of flat or indifferent fitness surfaces as applied to diversity and life span is clearly warranted.     

Measuring Caenorhabditis elegans Life Span on Solid Media

Aging is a degenerative process characterized by a progressive deterioration of cellular components and organelles resulting in mortality. The nematode Caenorhabditis elegans has emerged as a principal model used to study the biology of aging. Because virtually every biological subsystem undergoes functional decline with increasing age, life span is the primary endpoint of interest when considering total rate of aging. In nematodes, life span is typically defined as the number of days an animal remains responsive to external stimuli. Nematodes can be propagated either in liquid media or on solid media in plates, and techniques have been developed for measuring life span under both conditions. Here we present a generalized protocol for measuring life span of nematodes maintained on solid nematode growth media and fed a diet of UV-killed bacteria. These procedures can easily be adapted to assay life span under various common conditions, including a diet consisting of live bacteria, dietary restriction, and RNA interference.Open in a separate windowClick here to view.^{(78M, flv)}     

Senescence Is More Important in the Natural Lives of Long- Than Short-Lived Mammals

Background

Senescence has been widely detected among mammals, but its importance to fitness in wild populations remains controversial. According to evolutionary theories, senescence occurs at an age when selection is relatively weak, which in mammals can be predicted by adult survival rates. However, a recent analysis of senescence rates found more age-dependent mortalities in natural populations of longer lived mammal species. This has important implications to ageing research and for understanding the ecological relevance of senescence, yet so far these have not been widely appreciated. We re-address this question by comparing the mean and maximum life span of 125 mammal species. Specifically, we test the hypothesis that senescence occurs at a younger age relative to the mean natural life span in longer lived species.

Methodology/Principal Findings

We show, using phylogenetically-informed generalised least squares models, a significant log-log relationship between mean life span, as calculated from estimates of adult survival for natural populations, and maximum recorded life span among mammals (R² = 0.57, p<0.0001). This provides further support for a key prediction of evolutionary theories of ageing. The slope of this relationship (0.353±0.052 s.e.m.), however, indicated that mammals with higher survival rates have a mean life span representing a greater fraction of their potential maximum life span: the ratio of maximum to mean life span decreased significantly from >10 in short-lived to ∼1.5 in long-lived mammal species.

Conclusions/Significance

We interpret the ratio of maximum to mean life span to be an index of the likelihood an individual will experience senescence, which largely determines maximum life span. Our results suggest that senescence occurs at an earlier age relative to the mean life span, and therefore is experienced by more individuals and remains under selection pressure, in long- compared to short-lived mammals. A minimum rate of somatic degradation may ultimately limit the natural life span of mammals. Our results also indicate that senescence and modulating factors like oxidative stress are increasingly important to the fitness of longer lived mammals (and vice versa).     

Blade life span,structural investment,and nutrient allocation in giant kelp

The turnover of plant biomass largely determines the amount of energy flowing through an ecosystem and understanding the processes that regulate turnover has been of interest to ecologists for decades. Leaf life span theory has proven useful in explaining patterns of leaf turnover in relation to resource availability, but the predictions of this theory have not been tested for macroalgae. We measured blade life span, size, thickness, nitrogen content, pigment content, and maximum photosynthetic rate (P _max) in the giant kelp (Macrocystis pyrifera) along a strong resource (light) gradient to test whether the predictions of leaf life span theory applied to this alga. We found that shorter blade life spans and larger blade areas were associated with increased light availability. In addition, nitrogen and P _max decreased with blade age, and their decrease was greater in shorter lived blades. These observations are generally consistent with patterns observed for higher plants and the prevailing theory of leaf life span. By contrast, variation observed in pigments of giant kelp was inconsistent with that predicted by leaf life span theory, as blades growing in the most heavily shaded portion of the forest had the lowest chlorophyll content. This result may reflect the dual role of macroalgal blades in carbon fixation and nutrient absorption and the ability of giant kelp to modify blade physiology to optimize the acquisition of light and nutrients. Thus, the marine environment may place demands on resource acquisition and allocation that have not been previously considered with respect to leaf life span optimization.     

High sexual signalling rates of young individuals predict extended life span in male Mediterranean fruit flies

In a laboratory study, we monitored the lifetime sexual signalling (advertisement) of wild male Mediterranean fruit flies, and we tested the hypothesis that high lifetime intensity of sexual signalling indicates high survival probabilities. Almost all males exhibited signalling and individual signalling rates were highly variable from the beginning of the adults maturity and throughout their life span (average life span 62.3 days). Sexual signalling rates after day 10 (peak maturity) were consistently high until about 1 week before death. There was a positive relationship between daily signalling rates and life span, and an increase in signalling level by one unit over all times was associated with an approximately 50% decrease in mortality rate. Signalling rates early in adult life (day 6–20) were higher in the longest-lived than in the shortest-lived flies. These results support the hypothesis that intense sexual signalling indicates longer life span. We discuss the importance of age-specific behavioural studies for understanding the evolution of male life histories.     

Measuring Replicative Life Span in the Budding Yeast

Aging is a degenerative process characterized by a progressive deterioration of cellular components and organelles resulting in mortality. The budding yeast Saccharomyces cerevisiae has been used extensively to study the biology of aging, and several determinants of yeast longevity have been shown to be conserved in multicellular eukaryotes, including worms, flies, and mice ¹. Due to the lack of easily quantified age-associated phenotypes, aging in yeast has been assayed almost exclusively by measuring the life span of cells in different contexts, with two different life span paradigms in common usage ². Chronological life span refers to the length of time that a mother cell can survive in a non-dividing, quiescence-like state, and is proposed to serve as a model for aging of post-mitotic cells in multicellular eukaryotes. Replicative life span, in contrast, refers the number of daughter cells produced by a mother cell prior to senescence, and is thought to provide a model of aging in mitotically active cells. Here we present a generalized protocol for measuring the replicative life span of budding yeast mother cells. The goal of the replicative life span assay is to determine how many times each mother cell buds. The mother and daughter cells can be easily differentiated by an experienced researcher using a standard light microscope (total magnification 160X), such as the Zeiss Axioscope 40 or another comparable model. Physical separation of daughter cells from mother cells is achieved using a manual micromanipulator equipped with a fiber-optic needle. Typical laboratory yeast strains produce 20-30 daughter cells per mother and one life span experiment requires 2-3 weeks.Open in a separate windowClick here to view.^{(75M, flv)}     

Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress

Increasing cellular glucose uptake is a fundamental concept in treatment of type 2 diabetes, whereas nutritive calorie restriction increases life expectancy. We show here that increased glucose availability decreases Caenorhabditis elegans life span, while impaired glucose metabolism extends life expectancy by inducing mitochondrial respiration. The histone deacetylase Sir2.1 is found here to be dispensable for this phenotype, whereas disruption of aak-2, a homolog of AMP-dependent kinase (AMPK), abolishes extension of life span due to impaired glycolysis. Reduced glucose availability promotes formation of reactive oxygen species (ROS), induces catalase activity, and increases oxidative stress resistance and survival rates, altogether providing direct evidence for a hitherto hypothetical concept named mitochondrial hormesis or "mitohormesis." Accordingly, treatment of nematodes with different antioxidants and vitamins prevents extension of life span. In summary, these data indicate that glucose restriction promotes mitochondrial metabolism, causing increased ROS formation and cumulating in hormetic extension of life span, questioning current treatments of type 2 diabetes as well as the widespread use of antioxidant supplements.     

Longevity and metabolism in Drosophila melanogaster: genetic correlations between life span and age-specific metabolic rate in populations artificially selected for long life

We measured age-specific metabolic rates in 2861 individual Drosophila melanogaster adult males to determine how genetic variation in metabolism is related to life span. Using recombinant inbred (RI) lines derived from populations artificially selected for long life, resting metabolic rates were measured at 5, 16, 29, and 47 days posteclosion, while life spans were measured in the same genotypes in mixed-sex population cages and in single-sex vials. We observed much heritable variation between lines in age-specific metabolic rates, evidence for genotype x age interaction, and moderate to large heritabilities at all ages except the youngest. Four traits exhibit evidence of coordinate genetic control: day 16 and day 29 metabolic rates, life span in population cages, and life span in vials. Quantitative trait loci (QTL) for those traits map to the same locations on three major chromosomes, and additive genetic effects are all positively correlated. In contrast, metabolic rates at the youngest and oldest ages are unrelated to metabolic rates at other ages and to survival. We suggest that artificial selection for long life via delayed reproduction also selects for increased metabolism at intermediate ages. Contrary to predictions of the "rate of living" theory, we find no evidence that metabolic rate varies inversely with survival, at the level of either line means or additive effects of QTL.     

Effect of pollination on floral longevity and costs of delaying fertilization in the out-crossing Polygala vayredae Costa (Polygalaceae)

Background and Aims

The effect of pollination on flower life span has been widely studied, but so far little attention has been paid to the reproductive consequences of delayed pollination in plants with long floral life spans. In the present study, Polygala vayredae was used to answer the following questions. (1) How does male and female success affect the floral longevity of individual flowers? (2) How does delaying fertilization affect the female fitness of this species?

Methods

Floral longevity was studied after experimental pollinations involving male and/or female accomplishment, bagging and open pollination. The reproductive costs of a delay in the moment of fertilization were evaluated through fruit set, seed–ovule ratio and seed weight, after pollination of flowers that had been bagged for 2–18 d.

Key Results

Senescence of the flowers of P. vayredae was activated by pollen reception on the stigmatic papillae, while pollen removal had no effect on floral longevity. Nonetheless, a minimum longevity of 8 d was detected, even after successful pollination and pollen dissemination. This period may be involved with the enhancement of male accrual rates, as the female accomplishment is generally achieved after the first visit. Floral life span of open-pollinated flowers was variable and negatively correlated with pollinator visitation rates. Delayed pollination had a major impact on the reproductive success of the plant, with fruit set, seed–ovule ratio and seed weight being significantly diminished with the increase of flower age at the moment of fertilization.

Conclusions

A strong relationship between pollination and floral longevity was observed. Flowers revealed the ability to extend or reduce their longevity, within some limits, in response to the abundance of efficient pollinators (i.e. reproductive fulfilment rates). Furthermore, with scarce or unpredictable pollinators, a long floral life span could maintain the opportunity for fertilization but would also have reproductive costs on production of offspring. Reduced female fitness late in the flower''s life could shift the cost–benefit balance towards a shorter life span, partially counteracting the selection for longer floral life span potentially mediated by scarce pollination services.Key words: Delayed pollination, endemic species, flower longevity, life span, pollen limitation, pollination, pollinator scarcity, Polygala vayredae, Polygalaceae, reproductive consequences, secondary pollen presentation     

The effects of temperature on the longevity of adultDrosophila willistoni infected withNosema kingi

The effects of various temperatures on adultDrosophila willistoni Sturtevant infected withNosema kingi Kramer were studied. The minimal and maximal temperatures for the normal development of both the host and parasite were 17±2°C and 27±2°C respectively. 22±2°C appeared to be the optimal temperature rature for rearing both the host and parasite since the life span of the flies and the parasite burden were greatest at this temperature. Generally, as the temperature increased, the life span of the adultD. willistoni decreased.     

Comparison of life span of erythrocytes in some inbred strains of mouse using 14C-labelled glycine.

The erythrocyte life span in four inbred strains of mice--C57BL/10ScSnPh, B10.LP, BALB/c and CBA/JPh--was determined by means of erythrocyte labelling with 14C-glycine. Experimental data [decrease of 14C-activity of washed erythrocytes], corrected for blood loss, reincorporation of the label and delay in label incorporation during the initial period, were treated by a novel mathematical procedure based on the death probability function of the form: mu [t] = a + btlambda. The mean erythrocyte life span calculated using this function was, in the given sequence of strains, 42.1 +/- 0.6, 41.3 +/- 1.2, 39.3 +/- 0.9 and 38.6 +/- 0.6 days respectively. The rate of "random" destruction of erythrocytes was 1.20, 1.31, 0.70 and 0.63% of the total number of erythrocytes per day and a "mean potential" erthrocyte life span was found to be 58.9, 59.9, 46.2 and 44.5 days respectively. All the given parameters have similar numerical values in related strains and are apparently genetically conditioned. The erythrocyte life span determined simultaneously using DF32P labelling in the C57BL/10ScSnPh strain was 47.4 +/- 1.0 days. The implications of the results yielded by these two techniques is discussed.     

The effect of different light regimes on adult life span in Drosophila melanogaster is partly mediated through reproductive output

The effects of different light regimes on the fitness of organisms have typically been studied using mean or median adult life span as the sole index of physiological well-being. It is, however, known that life span is inversely related to reproductive output in many species. Moreover, the effects of a given environmental treatment on life span can be due to effects on either age-independent mortality or the "rate of aging," or a combination of both. Drawing evolutionary inferences from the effects of light regime on mean or median adult life span alone is difficult and, at best, speculative. We examined the effects of constant light (LL), alternating light-dark cycles (LD 12:12 h), and constant darkness (DD) on the life span of reproducing and virgin flies in four populations of Drosophila melanogaster and also estimated lifetime fecundity in the three light regimes. The light regime effects on life span were further dissected by examining the age-independent mortality and the Gompertz rate of aging under the three light regimes. While mean adult life span of reproducing males and females and virgin females was significantly shorter in LL compared to LD 12:12 h and DD, life-time egg production was highest in LL. Life span of virgin males was not significantly affected by light regime. The rate of aging in reproducing females was higher in LL as compared to DD, whereas age-independent mortality was higher in DD. As reproductive output, especially early in life, is a far more significant contributor to fitness than is life span, our results suggest that the earlier reported deleterious effects of LL on fitness are partly an artifact of examining life span alone, without considering other components of adult fitness that trade off with life span. Our results suggest that detailed investigation of the effects of light regime on the physiological and behavioral processes that accompany reproduction is necessary to fully understand the effects of different light regimes on adult fitness in Drosophila.     

Changes in Antioxidative Protection in Bean Cotyledons During Natural and Continuous Irradiation-Accelerated Senescence

We employed continuous irradiation (CL) for induction of premature senescence caused by enhanced production of reactive oxygen species. As a model plant we used bean (Phaseolus vulgaris L. cv. Jantar) cotyledons because they have well defined and a quite short life span. Senescence of bean cotyledons induced by CL progressed more rapidly than natural senescence: the life span of CL cotyledons was 13 d compared to 16 d in controls (C). Chl content was significantly lower in 10- and 13-d-old CL plants than in C plants and the change with age was not statistically significant. Activities of all antioxidative enzymes declined either with senescence onset or during whole life span. Activity of antioxidative enzymes, except ascorbate peroxidase, was lower in CL plants compared to C plants. On the contrary, contents of non-enzymatic antioxidants -carotene and ascorbate were higher in CL plants than in C plants. No significant difference, except in the youngest cotyledons, was observed in glutathione content.