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Ageing Res Rev,
2024]
This paper addresses how long lifespan can be extended via multiple interventions, such as dietary supplements [e.g., curcumin, resveratrol, sulforaphane, complex phytochemical mixtures (e.g., Moringa, Rhodiola)], pharmaceutical agents (e.g., metformin), caloric restriction, intermittent fasting, exercise and other activities. This evaluation was framed within the context of hormesis, a biphasic dose response with specific quantitative features describing the limits of biological/phenotypic plasticity for integrative biological endpoints (e.g., cell proliferation, memory, fecundity, growth, tissue repair, stem cell population expansion/differentiation, longevity). Evaluation of several hundred lifespan extending agents using yeast, nematode (Caenorhabditis elegans), multiple insect and other invertebrate and vertebrate models (e.g., fish, rodents), revealed they responded in a manner [average (mean/median) and maximum lifespans] consistent with the quantitative features [i.e., 30-60% greater at maximum (Hormesis Rule)] of the hormetic dose response. These lifespan extension features were independent of biological model, inducing agent, endpoints measured and mechanism. These findings indicate that hormesis describes the capacity to extend life via numerous agents and activities and that the magnitude of lifespan extension is modest, in the percentage, not fold, range. These findings have important implications for human aging, genetic diseases/environmental stresses and lifespan extension, as well as public health practices and long-term societal resource planning.
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Curr Opin Neurobiol,
1998]
Ion channels in the amiloride-sensitive Na+ channel/degenerin (NaC/DEG) family of cation channels have very diverse functions. They can be constitutively active (e.g. the epithelial Na+ channel), gated by a ligand (e.g. the peptide-gated channel FaNaC or H+-gated cation channels [ASICs]) or possibly activated by stretch (degenerins of Caenorhabditis elegans). Despite this functional diversity, the heterologous expressed channels share the following properties: permeability to Na+, inhibition by the diuretic amiloride and no voltage gating. This review will focus on recent advances in this ion channel family, with special emphasis on H+-gated cation channels.
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Apoptosis,
2010]
Programmed cell death is used during developmental morphogenesis to eliminate superfluous cells or cells with inappropriate developmental potential (e.g., self-reactive immune cells, tumorigenic cells). Recent work in genetic models has led to a number of key observations, revealing signal transduction pathways and identifying new roles for genes previously studied in corpse removal (e.g., removal of broken synapses in the nervous system). Further, studies using mouse models have suggested a role for removal of apoptotic cells in the establishment or maintenance of immune tolerance. In this review, we survey current knowledge of phagocytic pathways derived from studies in the nematode (Caenorhabditis elegans), the fly (Drosophila melanogaster), and mouse (Mus musculus) model systems.
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Trends Biochem Sci,
2001]
Serine proteinase inhibitors are encoded by a large gene family of long evolutionary standing. Recent discoveries of parasite proteins that inhibit human serine proteinases, together with the complete genomic sequence from Caenorhabditis elegans, have provided a set of new serine proteinase inhibitors from more primitive metazoan animals such as nematodes. The structural features (e.g. reactive centre residues), gene organization (including intron arrangements) and inhibitory function and targets (e.g. inflammatory and coagulation pathway proteinase) all contribute important new insights into proteinase inhibitor evolution. Some parasite products have evolved that block enzymes in the mammalian host, but the human host responds with a significant immune response to the parasite inhibitors. Thus, infection produces a finely balanced conflict between host and pathogen at the molecular level, and this might have accelerated the evolution of these proteins in parasitic species as well as their hosts.
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J Dev Biol,
2023]
Whole genome duplication (WGD) or polyploidization can occur at the cellular, tissue, and organismal levels. At the cellular level, tetraploidization has been proposed as a driver of aneuploidy and genome instability and correlates strongly with cancer progression, metastasis, and the development of drug resistance. WGD is also a key developmental strategy for regulating cell size, metabolism, and cellular function. In specific tissues, WGD is involved in normal development (e.g., organogenesis), tissue homeostasis, wound healing, and regeneration. At the organismal level, WGD propels evolutionary processes such as adaptation, speciation, and crop domestication. An essential strategy to further our understanding of the mechanisms promoting WGD and its effects is to compare isogenic strains that differ only in their ploidy. <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) is emerging as an animal model for these comparisons, in part because relatively stable and fertile tetraploid strains can be produced rapidly from nearly any diploid strain. Here, we review the use of Caenorhabditis polyploids as tools to understand important developmental processes (e.g., sex determination, dosage compensation, and allometric relationships) and cellular processes (e.g., cell cycle regulation and chromosome dynamics during meiosis). We also discuss how the unique characteristics of the <i>C. elegans</i> WGD model will enable significant advances in our understanding of the mechanisms of polyploidization and its role in development and disease.
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J Physiol Biochem,
2007]
The use of microarrays to evaluate the transcriptome has transformed our view of biology. In addition to the focused, hypothesis-testing studies that we have traditionally conducted in cell biology, we are now able to see global changes within the entire system of the cell in response to a treatment. By examining a biological question under multiple complementary perturbations model systems (e.g. yeast, C. Elegans) have revealed new complexity that would have been impossible to see on a gene-by-gene approach. Unfortunately, beyond the use of transcript profiles to define the molecular signature of diseases (e.g. cancer), transcriptomics has not been extensively used to study intestinal biology. This review will provide a roadmap for effective use of gene expression profiling for biological research and will review some of the microarray work that has been done to better understand the nature of intestinal development and enterocyte differentiation.
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Cell Signal,
2010]
GH/insulin/IGF-1 signaling is a vital pathway e.g. in the regulation of protein synthesis and glucose metabolism. However, mouse dwarf strains which exhibit reduced GH secretion and subsequently a decline in IGF-1 signaling can live longer than their wild type counterparts. There is striking evidence indicating that the IGF-1/PI-3K/AKT signaling enhances growth of animals during development but later in life can potentiate the aging process. This conserved pleiotropy has been called the insulin/IGF-1 paradox. In Caenorhabditiselegans, the decline in this pathway activates the DAF-16 gene, an ortholog of mammalian FoxO genes, which regulate stress resistance and longevity. The mammalian PI-3K/AKT pathway also activates the NF-kappaB signaling that inhibits apoptosis and triggers inflammatory responses. Many longevity genes, e.g. FoxOs and SIRT1, are inhibitors of NF-kappaB signaling. We will discuss the evidence that insulin/IGF-1 signaling can enhance the NF-kappaB signaling and subsequently potentiate the aging process and aggravate age-related degenerative diseases.
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Biochim Biophys Acta,
2016]
Testing the predictions of the Mitochondrial Free Radical Theory of Ageing (MFRTA) has provided a deep understanding of the role of reactive oxygen species (ROS) and mitochondria in the aging process. However those data, which support MFRTA are in the majority correlative (e.g. increasing oxidative damage with age). In contrast the majority of direct experimental data contradict MFRTA (e.g. changes in ROS levels do not alter longevity as expected). Unfortunately, in the past, ROS measurements have mainly been performed using isolated mitochondria, a method which is prone to experimental artifacts and does not reflect the complexity of the in vivo process. New technology to study different ROS (e.g. superoxide or hydrogen peroxide) in vivo is now available; these new methods combined with state-of-the-art genetic engineering technology will allow a deeper interrogation of, where, when and how free radicals affect aging and pathological processes. In fact data that combine these new approaches, indicate that boosting mitochondrial ROS in lower animals is a way to extend both healthy and maximum lifespan. In this review, I discuss the latest literature focused on the role of mitochondrial ROS in aging, and how these new discoveries are helping to better understand the role of mitochondria in health and disease. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.
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Int J Mol Sci,
2019]
Aging is a natural phenomenon that occurs in all living organisms. In humans, aging is associated with lowered overall functioning and increased mortality out of the risk for various age-related diseases. Hence, researchers are pushed to find effective natural interventions that can promote healthy aging and extend lifespan. Royal jelly (RJ) is a natural product that is fed to bee queens throughout their entire life. Thanks to RJ, bee queens enjoy an excellent reproductive function and lengthened lifespan compared with bee workers, despite the fact that they have the same genome. This review aimed to investigate the effect of RJ and/or its components on lifespan/healthspan in various species by evaluating the most relevant studies. Moreover, we briefly discussed the positive effects of RJ on health maintenance and age-related disorders in humans. Whenever possible, we explored the metabolic, molecular, and cellular mechanisms through which RJ can modulate age-related mechanisms to extend lifespan. RJ and its ingredients-proteins and their derivatives e.g., royalactin; lipids e.g., 10-hydroxydecenoic acid; and vitamins e.g., pantothenic acid-improved healthspan and extended lifespan in worker honeybees <i>Apis mellifera</i>, <i>Drosophila Melanogaster</i> flies, <i>Gryllus bimaculatus</i> crickets, silkworms, <i>Caenorhabditis elegans</i> nematodes, and mice. The longevity effect was attained via various mechanisms: downregulation of insulin-like growth factors and targeting of rapamycin, upregulation of the epidermal growth factor signaling, dietary restriction, and enhancement of antioxidative capacity. RJ and its protein and lipid ingredients have the potential to extend lifespan in various creatures and prevent senescence of human tissues in cell cultures. These findings pave the way to inventing specific RJ anti-aging drugs. However, much work is needed to understand the effect of RJ interactions with microbiome, diet, activity level, gender, and other genetic variation factors that affect healthspan and longevity.
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Immunol Rev,
1998]
This article focuses on four human carboxypeptidases (CPs): two metallo-CPs and two serine CPs. The metallo-CPs are members of the so-called B-type regulatory CP family, as they cleave only the C-terminal basic amino acids Arg or Lys. The plasma membrane-bound CPM and the mainly, but not exclusively, intracellular CPD are surveyed from this group of enzymes. These enzymes can regulate peptide hormone activity at the cell surface and possibly intracellularly after receptor-mediated endocytosis and may also participate in peptide hormone processing. The serine CPs, as their name indicates, contain a serine residue in the active center essential for catalytic activity that reacts with organophosphorus inhibitors. Prolylcarboxypeptidase (PRCP) (angiotensinase C) and deamidase (cathepsin A, lysosomal protective protein) are discussed here. These two enzymes are highly concentrated in lysosomes; however, they may also be active extracellularly after their release from lysosomes in soluble form or in a plasma membrane-bound complex. Whereas deamidase cleaves a variety of peptides with C-terminal or penultimate hydrophobic residues (e.g. substance P, angiotensin I, bradykinin, endothelin, fMet-Leu-Phe). PRCP cleaves only peptides with a penultimate Pro residue (e.g. des-Arg9-bradykinin, angiotensin II). These enzymes may also be involved in terminating signal transduction by inactivating peptide ligands after receptor endocytosis.