Alternative mitochondrial fuel extends life span

In this issue of Cell Metabolism, Ristow and colleagues (Zarse et?al., 2012) elucidate a conserved mechanism through which reduced insulin-IGF1 signaling activates an AMP-kinase-driven metabolic shift toward oxidative proline metabolism. This, in turn, produces an adaptive mitochondrial ROS signal that extends worm life span. These findings further bolster the concept of mitohormesis as a critical component of conserved aging and longevity pathways.     

Leaf life span of floating-leaved plants

Photosynthetic capacity of floating-leaved plants is relatively high comparable with terrestrial herbaceous plants, though floating-leaved plants have a much smaller biomass with a leaf area index seldom exceeding 2m²m^-2. Their rather small biomass accumulation is related to higher turnover of leaf biomass or shorter leaf life span. Life span of floating leaves reported in the literature ranged mostly from 13 to 35 days, shorter than that of any other groups of herbaceous macrophytes. Floating-leaved plants are known to show considerably high plasticity in their leaf form. Leaf life span could be prolonged for Nymphoides peltata (Gmel.) O. Kuntze grown in a terrestrial environment and for emergent leaves of Nelumbo nucifera Gaertn. Their short leaf life span seems to be closely related to the fact that old leaves covered by newly formed ones are inevitably compelled to be submerged and lose their function as a photosynthetic apparatus.Abbreviations LAI leaf area index - PFD photosynthetic photon flux density     

Genetics of life span in mice

Thymic involution that occurs earlier in some individuals than others may be the result of complex interactions between genetic factors and the environment. Such interactions may produce defects of thymus-dependent immune regulation associated with susceptibility to developing autoimmune diseases, malignancy, and an increased number of infections associated with aging.The major histocompatibility complex may be important in determining profiles of cause of death and length of life in mice. Genetic influences on life span involve interactions between loci and allelic interactions during life which may change following viral infections or exposure to other environmental factors. We have used different experimental protocols to study the influence of H-2 on life span and found that interactions between genetic regions, are inconsistent, particularly when comparing mice infected or not infected with Sendai virus.Genes important for life span need to be studied against many genetic backgrounds and under differing environmental conditions because of the complexity of the genetics of life span. Several genetic models were used to demonstrate that the MHC is a marker of life span in backcross and intercross male mice of the H-2^d and H-2^b genotypes in B10 congenic mice. Females lived longer than males in backcross and intercross mice, while males lived longer than females in B10 congenics. H-2^d was at a disadvantage for life span in backcross mice of the dilute brown and brown males exposed to Sendai infection, but intercross mice not exposed to Sendai virus of the same genotype were not at a disadvantage. H-2^d mice were not disadvantaged when compared to H-2^b in B10 congenics that had not been exposed to Sendai virus infection but the reverse was true when they were exposed. Overall, all our studies suggest that genetic influences in life span may involve interactions between loci and many allelic interactions in growing animals or humans. These genetic influences on life span may vary after they are exposed to infections or other environmental conditions. This paper emphasizes the need to use several genetic models, especially animals that have been monitored for infections, to study the genetics of life span.     

Antagonizing Methuselah to extend life span

A recent report describes the identification through the use of in vitro selection of a peptide that antagonizes Methuselah signaling in Drosophila in vitro and extends fly life span in vivo.     

Post-reproductive life span and demographic stability

Recent field studies suggest that it is common in nature for animals to outlive their reproductive viability. Post-reproductive life span has been observed in a broad range of vertebrate and invertebrate species. But post-reproductive life span poses a paradox for traditional theories of life history evolution. The commonly cited explanation is the “grandmother hypothesis”, which applies only to higher, social mammals. We propose that post-reproductive life span evolves to stabilize predator-prey population dynamics, avoiding local extinctions. In the absence of senescence, juveniles would be the most susceptible age class. If juveniles are the first to disappear when predation pressure is high, this amplifies the population’s risk of extinction. A class of older, senescent individuals can help shield the juveniles from predation, stabilizing demographics and avoiding extinction. If, in addition, the life history is arranged so that the older individuals are no longer fertile, the stabilizing effect is further enhanced.     

How the genome got a life span

In the space of little more than a decade, ideas of the human genome have shifted significantly, with the emergence of the notion that the genome of an individual changes with development, age, disease, environmental inputs, and time. This paper examines the emergence of the genome with a life span, one that experiences drift, instability, and mutability, and a host of other temporal changes. We argue that developments in chromatin biology have provided the basis for this genomic embodiment of experience and exposure. We analyze how time has come to matter for the genome through chromatin, providing analysis of examples in which the human life course is being explored as a set of material changes to chromatin. A genome with a life span aligns the molecular and the experiential in new ways, shifting ideas of life stages, their interrelation, and the temporality of health and disease.     

Extending life span by increasing oxidative stress

Various nutritional, behavioral, and pharmacological interventions have been previously shown to extend life span in diverse model organisms, including Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, mice, and rats, as well as possibly monkeys and humans. This review aims to summarize published evidence that several longevity-promoting interventions may converge by causing an activation of mitochondrial oxygen consumption to promote increased formation of reactive oxygen species (ROS). These serve as molecular signals to exert downstream effects to ultimately induce endogenous defense mechanisms culminating in increased stress resistance and longevity, an adaptive response more specifically named mitochondrial hormesis or mitohormesis. Consistently, we here summarize findings that antioxidant supplements that prevent these ROS signals interfere with the health-promoting and life-span-extending capabilities of calorie restriction and physical exercise. Taken together and consistent with ample published evidence, the findings summarized here question Harman's Free Radical Theory of Aging and rather suggest that ROS act as essential signaling molecules to promote metabolic health and longevity.     

Cellular life span and the Warburg effect

Enhanced glycolysis is observed in most of cancerous cells and tissues, called as the Warburg effect. Recent advance in senescent biology implicates that the metabolic shift to enhanced glycolysis would be involved in the early stage during multi-step tumorigenesis in vivo. Enhanced glycolysis is essential both in the step of immortalization and transformation, as it renders cells resistant to oxidative stress and adaptive to hypoxic condition, respectively. ES, immortalized primary, and cancerous cells display the common concerted metabolic shift, including enhanced glycolysis with reduced mitochondrial respiration by poorly characterized mechanism. Discovery of a novel regulatory mechanism for such a metabolic shift might be essential for the future development of cancer diagnosis and anti-cancer therapy.     

The chronological life span of Saccharomyces cerevisiae

Simple model systems have played an important role in the discovery of fundamental mechanisms of aging. Studies in yeast, worms and fruit flies have resulted in the identification of proteins and signalling pathways that regulate stress resistance and longevity. New findings indicate that these pathways may have evolved to prevent damage and postpone aging during periods of starvation and may be conserved from yeast to mammals. We will review the yeast S. cerevisiae model system with emphasis on the chronological life span as a model system to study aging and the regulation of stress resistance in eukaryotes.     

Menopause in Blackfeet women--a life span perspective

A lifespan perspective, combining quantitative and qualitative approaches, is used to examine factors related to the timing of menopause in Blackfeet women of northern Montana (USA). Cross-sectional survey data demonstrate a median age at menopause using a status quo method of 51.6 years, and a mean age of 47.0 +/- 5.0 years among those women who had already experienced menopause. Age at menopause is inversely associated with age at menarche and having been breastfed, and positively associated with use of contraceptives, household income, and current or recent employment. Household income and age at menarche influence menopause age jointly in multivariate models. These and other patterns are examined in the lives of two women with very divergent ages at menopause. Although these data support an effect of early life influences on shaping reproductive trajectories that culminate in menopause, environmental factors and human agency during adult life may play a modifying role.     

A Bcl-xL timer sets platelet life span

Platelets are cell fragments lacking nuclei that play a key role in blood clotting. Using an impressive genetic screen involving ENU-mutagenesis of whole mice, Mason et al. (2007) report in this issue their identification of mutations in the antiapoptotic protein Bcl-x(L) that cause accelerated death of platelets leading to platelet deficiency.     

Genetic determinants of human health span and life span: progress and new opportunities

We review three approaches to the genetic analysis of the biology and pathobiology of human aging. The first and so far the best-developed is the search for the biochemical genetic basis of varying susceptibilities to major geriatric disorders. These include a range of progeroid syndromes. Collectively, they tell us much about the genetics of health span. Given that the major risk factor for virtually all geriatric disorders is biological aging, they may also serve as markers for the study of intrinsic biological aging. The second approach seeks to identify allelic contributions to exceptionally long life spans. While linkage to a locus on Chromosome 4 has not been confirmed, association studies have revealed a number of significant polymorphisms that impact upon late-life diseases and life span. The third approach remains theoretical. It would require longitudinal studies of large numbers of middle-aged sib-pairs who are extremely discordant or concordant for their rates of decline in various physiological functions. We can conclude that there are great opportunities for research on the genetics of human aging, particularly given the huge fund of information on human biology and pathobiology, and the rapidly developing knowledge of the human genome.