A novel classification system for evolutionary aging theories.

Theories of lifespan evolution are a source of confusion amongst aging researchers. After a century of aging research the dispute over whether the aging process is active or passive persists and a comprehensive and universally accepted theoretical model remains elusive. Evolutionary aging theories primarily dispute whether the aging process is exclusively adapted to favor the kin or exclusively non-adapted to favor the individual. Interestingly, contradictory data and theories supporting both exclusively programmed and exclusively non-programmed theories continue to grow. However, this is a false dichotomy; natural selection favors traits resulting in efficient reproduction whether they benefit the individual or the kin. Thus, to understand the evolution of aging, first we must understand the environment-dependent balance between the advantages and disadvantages of extended lifespan in the process of spreading genes. As described by distinct theories, different niches and environmental conditions confer on extended lifespan a range of fitness values varying from highly beneficial to highly detrimental. Here, we considered the range of fitness values for extended lifespan and develop a fitness-based framework for categorizing existing theories. We show that all theories can be classified into four basic types: secondary (beneficial), maladaptive (neutral), assisted death (detrimental), and senemorphic aging (varying between beneficial to detrimental). We anticipate that this classification system will assist with understanding and interpreting aging/death by providing a way of considering theories as members of one of these classes rather than consideration of their individual details.

Acute stress response modified by modest inhibition of growth hormone axis: a potential machinery of the anti-aging effect of calorie restriction.

Calorie restriction (CR) may exert antiaging effects by inhibiting the growth hormone (GH)/IGF-1 axis. The present study investigated the effect of modest inhibition of GH signaling on stress response and compared it with the effect of CR. Heterozygous (tg/-) rats of a transgenic strain of male rats, whose GH signaling was inhibited by overexpression of the anti-sense GH gene, and wild-type (WT) rats were used. Rats were fed ad libitum (AL) or 30% CR diets from 6 weeks of age. At 6 months of age, rats were killed between 0 and 8h after lipopolysaccharide (LPS) injection to evaluate the acute phase stress response. tg/- rats had less tissue injury, indicated by blood aspartate aminotransferase (AST) concentrations, than WT rats. Successive waves of incremental plasma TNF-α, IL-6, and interferon (IFN)-γ levels were also attenuated in tg/- rats. Activation of NF-κB, a redox-sensitive transcription factor, was slightly diminished in tg/- rats, whereas the AP-1 activity was increased. Similar trends were also observed in the CR groups as compared to the AL groups. The present results suggest an involvement of the GH/IGF-1 axis in the effect of CR for stress response, even if CR does not act solely through the GH axis.

Environmental impoverishment and aging alter object recognition, spatial learning, and dentate gyrus astrocytes.

Environmental and age-related effects on learning and memory were analysed and compared with changes observed in astrocyte laminar distribution in the dentate gyrus. Aged (20 months) and young (6 months) adult female albino Swiss mice were housed from weaning either in impoverished conditions or in enriched conditions, and tested for episodic-like and water maze spatial memories. After these behavioral tests, brain hippocampal sections were immunolabeled for glial fibrillary acid protein to identify astrocytes. The effects of environmental enrichment on episodic-like memory were not dependent on age, and may protect water maze spatial learning and memory from declines induced by aging or impoverished environment. In the dentate gyrus, the number of astrocytes increased with both aging and enriched environment in the molecular layer, increased only with aging in the polymorphic layer, and was unchanged in the granular layer. We suggest that long-term experience-induced glial plasticity by enriched environment may represent at least part of the circuitry groundwork for improvements in behavioral performance in the aged mice brain.

Dietary restriction and aging in rodents: a current view on its molecular mechanisms.

Dietary restriction (DR) is a robust non-genetic intervention that reduces morbidity and mortality in a range of organisms. This suggests the presence of an evolutionary-conserved pathway that regulates aging and lifespan in response to reduced food or energy intake. Recent genetic analyses have shown that single gene mutations could extend the lifespan, even in mammals. Many longevity genes are clustered into nutrient-sensing and metabolic adaptation pathways, which are also thought to be involved in the effect of DR. The responses of these mutant animals to DR in terms of lifespan or other aging phenotypes suggest that proteins encoded by these genes are involved in the effects of DR. This review focuses on the roles of fork head box O (FoxO) transcription factors, AMP-activated protein kinase (AMPK), and sirtuins (particularly SIRT1) in the effects of DR in rodents. FoxO transcription factors are mammalian orthologs of DAF-16, which is required for the lifespan extending effects of reduced insulin-like signaling in nematodes. A recent study in rodents suggested that FoxO1 is involved in the anti-neoplastic effects of DR. Although aak2 in nematodes (mammalian AMPK), Sir2 in yeast and Sir2.1 in nematodes (mammalian SIRT1) were also reported to be essential for lifespan extension by DR, the findings are thought to depend on the genetic backgrounds of the organisms and/or methods used to induce DR. In rodents, AMPK and SIRT1 are implicated in the metabolic regulation by long-term DR. Genetic and molecular dissection of the mechanisms underlying the effects of DR will provide us with knowledge of the basic aging processes, as well as insights into the development of DR mimetics, to extend the healthy lifespan in humans.