A wide range of human diseases, including cancer, has a striking age-dependent onset. However, the molecular mechanisms that connect aging and cancer are just beginning to be unraveled. FOXO transcription factors are promising candidates to serve as molecular links between longevity and tumor suppression. These factors are major substrates of the protein kinase Akt. In the presence of insulin and growth factors, FOXO proteins are relocalized from the nucleus to the cytoplasm and degraded via the ubiquitin-proteasome pathway.
The complex, highly integrative endocrine system regulates all aspects of somatic maintenance and reproduction and has been widely implicated as an important determinant of longevity in short-lived traditional model organisms of aging research. Genetic or experimental manipulation of hormone profiles in mice has been proven to definitively alter longevity. These hormonally induced lifespan extension mechanisms may not necessarily be relevant to humans and other long-lived organisms that naturally show successful slow aging.
Significant extension of lifespan in important mammalian species is bound to attract the attention not only of the aging research community, but also the media and the wider public. Two recent papers published by Harrison et al. (2009) in Nature and by Colman et al. (2009) in Science report increased longevity of mice fed with rapamycin and of rhesus monkeys undergoing caloric restriction, respectively. These papers have generated considerable debate in the aging community.
Can we extend human lifespan? Do we need to regulate lifestyle choices or can we simply pop a pill to make us live longer? These are questions raised by two new studies demonstrating significant lifespan extension in mice fed the drug rapamycin in their diet and in calorically restricted rhesus monkeys.
Studies of the molecular mechanisms that are involved in stress responses (environmental or physiological) have long been used to make links to disease states in humans. The nematode model organism, Caenorhabditis elegans, undergoes a state of hypometabolism called the 'dauer' stage. This period of developmental arrest is characterized by a significant reduction in metabolic rate, triggered by ambient temperature increase and restricted oxygen/ nutrients. C.
Vitamin E refers to a family of several compounds that possess a similar chemical structure comprising a chromanol ring with a 16-carbon side chain. The degree of saturation of the side chain, and positions and nature of methyl groups designate the compounds as tocopherols or tocotrienols. Vitamin E compounds have antioxidant properties due to a hydroxyl group on the chromanol ring. Recently, it has been suggested that vitamin E may also regulate signal transduction and gene expression.
This article proposes that behavioural advancement during mammalian evolution had been in part mediated through extension of total developmental time. Such time extensions would have resulted in increased numbers of neuronal precursor cells, hence larger brains and a disproportionate increase in the neocortex. Larger neocortical areas enabled new connections to be formed during development and hence expansion of existing behavioural circuits.
There is considerable interest in identifying small, drug-like compounds that slow aging in multiple species, particularly in mammals. Such compounds may prove to be useful in treating and retarding age-related disease in humans. Just as invertebrate models have been essential in helping us understand the genetic pathways that control aging, these model organisms are also proving valuable in discovering chemical compounds that influence longevity.
Caloric restriction, that is limiting food intake, is recognized in mammals as the best characterized and most reproducible strategy for extending lifespan, retarding physiological aging and delaying the onset of age-associated diseases. The aim of this mini review is to argue that p53 is the connection in the abilities of both the Sirt-1 pathway and the TOR pathway to impact on longevity of cells and organisms.
Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
The relationship of oxidative stress with maximum life span (MLSP) in different vertebrate species is reviewed. In all animal groups the endogenous levels of enzymatic and non-enzymatic antioxidants in tissues negatively correlate with MLSP and the most longevous animals studied in each group, pigeon or man, show the minimum levels of antioxidants. A possible evolutionary reason for this is that longevous animals produce oxygen radicals at a low rate. This has been analysed at the place where more than 90% of oxygen is consumed in the cell, the mitochondria.