Biochemistry, Genetics and Molecular Biology › Aging

Genetics, Aging, and Longevity in Model Organisms

Works Count: 53965

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Description

This cluster of papers explores the molecular mechanisms underlying aging, longevity, and age-related diseases. It covers topics such as oxidative stress, genetic regulation of lifespan, the impact of caloric restriction, mitochondrial function, RNA interference, inflammaging, insulin signaling, and proteostasis. The research spans model organisms like C. elegans and Drosophila to mammalian studies, providing insights into the fundamental processes of aging.

Keywords

Aging; Oxidative Stress; Longevity; Genetic Regulation; Caloric Restriction; Mitochondrial Function; RNAi; Inflammaging; Insulin Signaling; Proteostasis

The embryonic development of Drosophila melanogaster

1938-02-01

José A. Campos‐Ortega , Volker Hartenstein

The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans

1997-10-01

Scott Ogg , Suzanne Paradis , S Gottlieb +4 more

Why do we age?

2000-11-01

Thomas B. L. Kirkwood , Steven N. Austad

The Nematode Caenorhabditis elegans

1988-01-01

William B. Wood

In 1965 Sydney Brenner chose free-living nematode Caenorhabditis elegans as a promising model system for a concerted genetic, ultrastructural, and behavioral attack on development and function of a simple nervous … In 1965 Sydney Brenner chose free-living nematode Caenorhabditis elegans as a promising model system for a concerted genetic, ultrastructural, and behavioral attack on development and function of a simple nervous system. Since then, with help of a growing number of investigators, knowledge about biology of the worm has accumulated at a steadily accelerating pace to extent that C. elegans is now probably most completely understood metazoan in terms of anatomy, genetics, development, and behavior. The past few years have seen completion of two major long-term projects that provide new insights into C. elegans development and lay important groundwork for future investigation: completion of cell lineages of both sexes, from zygote to adult, and description of complete anatomy at level of electron microscope resolution, providing a complete wiring diagram of cell contacts in animal. Recent years have also brought first successes in molecularly cloning genes of developmental interest defined only by mutation, using transposon tagging as a generally applicable method for identification of desired DNA sequences. Reintroduction of cloned DNA sequences into genome has recently been accomplished. A physical map of genome has been assembled with a combination of cosmid and YAC genes. This Book of Worm serves as a reference source for C. elegans investigators as well as an introductory monograph for other biologists.

The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans

2000-02-01

Brenda J. Reinhart , Frank J. Slack , Michael Basson +5 more

THE GENETICS OF CAENORHABDITIS ELEGANS

1974-05-01

Sydney Brenner

ABSTRACT Methods are described for the isolation, complementation and mapping of mutants of Caenorhabditis elegans, a small free-living nematode worm. About 300 EMS-induced mutants affecting behavior and morphology have been … ABSTRACT Methods are described for the isolation, complementation and mapping of mutants of Caenorhabditis elegans, a small free-living nematode worm. About 300 EMS-induced mutants affecting behavior and morphology have been characterized and about one hundred genes have been defined. Mutations in 77 of these alter the movement of the animal. Estimates of the induced mutation frequency of both the visible mutants and X chromosome lethals suggests that, just as in Drosophila, the genetic units in C.elegans are large.

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Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA

2000-11-01

Amy E. Pasquinelli , Brenda J. Reinhart , Frank J. Slack +7 more

Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys

2009-07-09

Ricki J. Colman , Rozalyn M. Anderson , Sterling C. Johnson +7 more

Caloric restriction (CR), without malnutrition, delays aging and extends life span in diverse species; however, its effect on resistance to illness and mortality in primates has not been clearly established. … Caloric restriction (CR), without malnutrition, delays aging and extends life span in diverse species; however, its effect on resistance to illness and mortality in primates has not been clearly established. We report findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research. In a population of rhesus macaques maintained at the Wisconsin National Primate Research Center, moderate CR lowered the incidence of aging-related deaths. At the time point reported, 50% of control fed animals survived as compared with 80% of the CR animals. Furthermore, CR delayed the onset of age-associated pathologies. Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy. These data demonstrate that CR slows aging in a primate species.

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Genetic control of programmed cell death in the nematode C. elegans

1986-03-28

H J Ellis

Oxidative Stress, Caloric Restriction, and Aging

1996-07-05

Rajindar S. Sohal , Richard Weindruch

Under normal physiological conditions, the use of oxygen by cells of aerobic organisms generates potentially deleterious reactive oxygen metabolites. A chronic state of oxidative stress exists in cells because of … Under normal physiological conditions, the use of oxygen by cells of aerobic organisms generates potentially deleterious reactive oxygen metabolites. A chronic state of oxidative stress exists in cells because of an imbalance between prooxidants and antioxidants. The amount of oxidative damage increases as an organism ages and is postulated to be a major causal factor of senescence. Support for this hypothesis includes the following observations: (i) Overexpression of antioxidative enzymes retards the age-related accrual of oxidative damage and extends the maximum life-span of transgenic Drosophila melanogaster . (ii) Variations in longevity among different species inversely correlate with the rates of mitochondrial generation of the superoxide anion radical (O ·− 2 ) and hydrogen peroxide. (iii) Restriction of caloric intake lowers steady-state levels of oxidative stress and damage, retards age-associated changes, and extends the maximum life-span in mammals.

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Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans

2001-03-01

Heidi A. Tissenbaum , Leonard Guarente

IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice

2002-12-04

Martin Holzenberger , Joëlle Dupont , Bertrand Ducos +5 more

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Post-embryonic cell lineages of the nematode, Caenorhabditis elegans

1977-03-01

J.E. Sulston , H. Robert Horvitz

Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae

2000-09-22

Su-Ju Lin , Pierre‐Antoine Defossez , Leonard Guarente

Calorie restriction extends life-span in a wide variety of organisms. Although it has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species produced during … Calorie restriction extends life-span in a wide variety of organisms. Although it has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species produced during respiration, the mechanism by which this regimen slows aging is uncertain. Here, we mimicked calorie restriction in yeast by physiological or genetic means and showed a substantial extension in life-span. This extension was not observed in strains mutant for SIR2 (which encodes the silencing protein Sir2p) or NPT1 (a gene in a pathway in the synthesis of NAD, the oxidized form of nicotinamide adenine dinucleotide). These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD.

The embryonic cell lineage of the nematode Caenorhabditis elegans

1983-11-01

John Sulston , Einhard Schierenberg , John G. White +1 more

Evolution of ageing

1977-11-01

Thomas B. L. Kirkwood

Inflammaging and anti-inflammaging: A systemic perspective on aging and longevity emerged from studies in humans

2006-11-21

Claudio Franceschi , Miriam Capri , Daniela Monti +7 more

Green Fluorescent Protein as a Marker for Gene Expression

1994-02-11

Martin Chalfie , Yuan Tu , Ghia Euskirchen +2 more

A complementary DNA for the Aequorea victoria green fluorescent protein (GFP) produces a fluorescent product when expressed in prokaryotic ( Escherichia coli ) or eukaryotic ( Caenorhabditis elegans ) cells. … A complementary DNA for the Aequorea victoria green fluorescent protein (GFP) produces a fluorescent product when expressed in prokaryotic ( Escherichia coli ) or eukaryotic ( Caenorhabditis elegans ) cells. Because exogenous substrates and cofactors are not required for this fluorescence, GFP expression can be used to monitor gene expression and protein localization in living organisms.

Systematic functional analysis of the Caenorhabditis elegans genome using RNAi

2003-01-01

Ravi S. Kamath , Andrew Fraser , Dong Yan +7 more

A C. elegans mutant that lives twice as long as wild type

1993-12-01

Cynthia Kenyon , Jean Chang , Erin Gensch +2 more

Rapamycin fed late in life extends lifespan in genetically heterogeneous mice

2009-07-01

David E. Harrison , Randy Strong , Z. Dave Sharp +7 more

daf-2 , an Insulin Receptor-Like Gene That Regulates Longevity and Diapause in Caenorhabditis elegans

1997-08-15

Koutarou D. Kimura , Heidi A. Tissenbaum , Yanxia Liu +1 more

A C. elegans neurosecretory signaling system regulates whether animals enter the reproductive life cycle or arrest development at the long-lived dauer diapause stage. daf-2 , a key gene in the … A C. elegans neurosecretory signaling system regulates whether animals enter the reproductive life cycle or arrest development at the long-lived dauer diapause stage. daf-2 , a key gene in the genetic pathway that mediates this endocrine signaling, encodes an insulin receptor family member. Decreases in DAF-2 signaling induce metabolic and developmental changes, as in mammalian metabolic control by the insulin receptor. Decreased DAF-2 signaling also causes an increase in life-span. Life-span regulation by insulin-like metabolic control is analogous to mammalian longevity enhancement induced by caloric restriction, suggesting a general link between metabolism, diapause, and longevity.

Understanding the Odd Science of Aging

2005-02-01

Thomas B. L. Kirkwood

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Aging, Natural Death, and the Compression of Morbidity

1980-07-17

James F. Fries

The average length of life has risen from 47 to 73 years in this century, but the maximum life span has not increased. Therefore, survival curves have assumed an ever … The average length of life has risen from 47 to 73 years in this century, but the maximum life span has not increased. Therefore, survival curves have assumed an ever more rectangular form. Eighty per cent of the years of life lost to nontraumatic, premature death have been eliminated, and most premature deaths are now due to the chronic diseases of the later years. Present data allow calculation of the ideal average life span, approximately 85 years. Chronic illness may presumably be postponed by changes in life style, and it has been shown that the physiologic and psychologic markers of aging may be modified. Thus, the average age at first infirmity can be raised, thereby making the morbidity curve more rectangular. Extension of adult vigor far into a fixed life span compresses the period of senescence near the end of life. Health-research strategies to improve the quality of life require careful study of the variability of the phenomena of aging and how they may be modified.

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Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation

2009-05-22

Clifford P. Brangwynne , Christian R. Eckmann , David S. Courson +5 more

In sexually reproducing organisms, embryos specify germ cells, which ultimately generate sperm and eggs. In Caenorhabditis elegans, the first germ cell is established when RNA and protein-rich P granules localize … In sexually reproducing organisms, embryos specify germ cells, which ultimately generate sperm and eggs. In Caenorhabditis elegans, the first germ cell is established when RNA and protein-rich P granules localize to the posterior of the one-cell embryo. Localization of P granules and their physical nature remain poorly understood. Here we show that P granules exhibit liquid-like behaviors, including fusion, dripping, and wetting, which we used to estimate their viscosity and surface tension. As with other liquids, P granules rapidly dissolved and condensed. Localization occurred by a biased increase in P granule condensation at the posterior. This process reflects a classic phase transition, in which polarity proteins vary the condensation point across the cell. Such phase transitions may represent a fundamental physicochemical mechanism for structuring the cytoplasm.

The aging process.

1981-11-01

Denham Harman

Aging is the progressive accumulation of changes with time that are associated with or responsible for the ever-increasing susceptibility to disease and death which accompanies advancing age. These time-related changes … Aging is the progressive accumulation of changes with time that are associated with or responsible for the ever-increasing susceptibility to disease and death which accompanies advancing age. These time-related changes are attributed to the aging process. The nature of the aging process has been the subject of considerable speculation. Accumulating evidence now indicates that the sum of the deleterious free radical reactions going on continuously throughout the cells and tissues constitutes the aging process or is a major contributor to it. In mammalian systems the free radical reactions are largely those involving oxygen. Dietary manipulations expected to lower the rate of production of free radical reaction damage have been shown (i) to increase the life span of mice, rats, fruit flies, nematodes, and rotifers, as well as the "life span" of neurospora; (ii) to inhibit development of some forms of cancer; (iii) to enhance humoral and cell-mediated immune responses; and (iv) to slow development of amyloidosis and the autoimmune disorders of NZB and NZB/NZW mice. In addition, studies strongly suggest that free radical reactions play a significant role in the deterioration of the cardiovascular and central nervous systems with age. The free radical theory of aging provides reasonable explanations for age-associated phenomena, including (i) the relationship of the average life spans of mammalian species to their basal metabolic rates, (ii) the clustering of degenerative diseases in the terminal part of the life span, (iii) the beneficial effect of food restriction on life span, (iv) the greater longevity of females, and (v) the increase in autoimmune manifestations with age. It is not unreasonable to expect on the basis of present data that the healthy life span can be increased by 5-10 or more years by keeping body weight down, at a level compatible with a sense of well-being, while ingesting diets adequate in essential nutrients but designed to minimize random free radical reactions in the body.

The genetics of ageing

2010-03-23

Cynthia Kenyon

Extending Healthy Life Span—From Yeast to Humans

2010-04-15

Luigi Fontana , Linda Partridge , Valter D. Longo

When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet. A similar effect is seen when … When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet. A similar effect is seen when the activity of nutrient-sensing pathways is reduced by mutations or chemical inhibitors. In rodents, both dietary restriction and decreased nutrient-sensing pathway activity can lower the incidence of age-related loss of function and disease, including tumors and neurodegeneration. Dietary restriction also increases life span and protects against diabetes, cancer, and cardiovascular disease in rhesus monkeys, and in humans it causes changes that protect against these age-related pathologies. Tumors and diabetes are also uncommon in humans with mutations in the growth hormone receptor, and natural genetic variants in nutrient-sensing pathways are associated with increased human life span. Dietary restriction and reduced activity of nutrient-sensing pathways may thus slow aging by similar mechanisms, which have been conserved during evolution. We discuss these findings and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects.

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Inflamm‐aging: An Evolutionary Perspective on Immunosenescence

2000-06-01

Claudio Franceschi , Massimiliano Bonafé , Silvana Valensin +4 more

In this paper we extend the "network theory of aging," and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant … In this paper we extend the "network theory of aging," and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as "inflamm-aging," is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response. The rate of reaching the threshold of proinflammatory status over which diseases/disabilities ensue and the individual capacity to cope with and adapt to stressors are assumed to be complex traits with a genetic component. Finally, we argue that the persistence of inflammatory stimuli over time represents the biologic background (first hit) favoring the susceptibility to age-related diseases/disabilities. A second hit (absence of robust gene variants and/or presence of frail gene variants) is likely necessary to develop overt organ-specific age-related diseases having an inflammatory pathogenesis, such as atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes. Following this perspective, several paradoxes of healthy centenarians (increase of plasma levels of inflammatory cytokines, acute phase proteins, and coagulation factors) are illustrated and explained. In conclusion, the beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.

The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme

1993-11-19

Yuan Ji

Maintenance of C. elegans

2006-01-01

Theresa Stiernagle

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Oxidants, oxidative stress and the biology of ageing

2000-11-01

Toren Finkel , Nikki J. Holbrook

Alzheimer's Disease: The Amyloid Cascade Hypothesis

1992-04-10

John Hardy , Gerald A. Higgins

In both metazoan development and metastatic cancer, migrating cells must carry out a detailed, complex program of sensing cues, binding substrates, and moving their cytoskeletons. The linker cell in Caenorhabditis … In both metazoan development and metastatic cancer, migrating cells must carry out a detailed, complex program of sensing cues, binding substrates, and moving their cytoskeletons. The linker cell in Caenorhabditis elegans males undergoes a stereotyped migration that guides gonad organogenesis, occurs with precise timing, and requires the nuclear hormone receptor NHR-67. To better understand how this occurs, we performed RNA-seq of individually staged and dissected linker cells, comparing transcriptomes from linker cells of third-stage (L3) larvae, fourth-stage (L4) larvae, and nhr-67-RNAi–treated L4 larvae. We observed expression of 8,000–10,000 genes in the linker cell, 22–25% of which were up- or down-regulated 20-fold during development by NHR-67. Of genes that we tested by RNAi, 22% (45 of 204) were required for normal shape and migration, suggesting that many NHR-67–dependent, linker cell-enriched genes play roles in this migration. One unexpected class of genes up-regulated by NHR-67 was tandem pore potassium channels, which are required for normal linker-cell migration. We also found phenotypes for genes with human orthologs but no previously described migratory function. Our results provide an extensive catalog of genes that act in a migrating cell, identify unique molecular functions involved in nematode cell migration, and suggest similar functions in humans.

The Hallmarks of Aging

2013-06-01

Carlos López-Otı́n , Marı́a A. Blasco , Linda Partridge +2 more

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Mechanisms and Functions of Cell Death

1991-11-01

Ronald Ellis , Junying Yuan , H. Robert Horvitz

Cells organize many of their biochemical reactions in non-membrane compartments. Recent evidence has shown that many of these compartments are liquids that form by phase separation from the cytoplasm. Here … Cells organize many of their biochemical reactions in non-membrane compartments. Recent evidence has shown that many of these compartments are liquids that form by phase separation from the cytoplasm. Here we discuss the basic physical concepts necessary ...Read More

The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14

1993-12-01

Rosalind C. Lee , Rhonda Feinbaum , Victor Ambros

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Accumulation of Deficits as a Proxy Measure of Aging

2001-01-01

Arnold B. Mitnitski , Alexander Mogilner , Kenneth Rockwood

This paper develops a method for appraising health status in elderly people. A frailty index was defined as the proportion of accumulated deficits (symptoms, signs, functional impairments, and laboratory abnormalities). … This paper develops a method for appraising health status in elderly people. A frailty index was defined as the proportion of accumulated deficits (symptoms, signs, functional impairments, and laboratory abnormalities). It serves as an individual state variable, reflecting severity of illness and proximity to death. In a representative database of elderly Canadians we found that deficits accumulated at 3% per year, and show a gamma distribution, typical for systems with redundant components that can be used in case of failure of a given subsystem. Of note, the slope of the index is insensitive to the individual nature of the deficits, and serves as an important prognostic factor for life expectancy. The formula for estimating an individual's life span given the frailty index value is presented. For different patterns of cognitive impairments the average within-group index value increases with the severity of the cognitive impairment, and the relative variability of the index is significantly reduced. Finally, the statistical distribution of the frailty index sharply differs between well groups (gamma distribution) and morbid groups (normal distribution). This pattern reflects an increase in uncompensated deficits in impaired organisms, which would lead to illness of various etiologies, and ultimately to increased mortality. The accumulation of deficits is as an example of a macroscopic variable, i.e., one that reflects general properties of aging at the level of the whole organism rather than any given functional deficiency. In consequence, we propose that it may be used as a proxy measure of aging.

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The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms

1999-10-01

Matt Kaeberlein , Mitch McVey , Leonard Guarente

Matt Kaeberlein, Mitch McVey, and Leonard Guarente Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 USA Matt Kaeberlein, Mitch McVey, and Leonard Guarente Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 USA

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C. elegans: des neurones et des gènes

2003-06-01

Christelle Gally , Jean‐Louis Bessereau

Que peut nous apprendre un ver sur le fonctionnement du cerveau humain ? Les données acquises sur le système nerveux du nématode Caenorhabditis elegans démontrent l'existence d'une fascinante conservation de … Que peut nous apprendre un ver sur le fonctionnement du cerveau humain ? Les données acquises sur le système nerveux du nématode Caenorhabditis elegans démontrent l'existence d'une fascinante conservation de la biologie moléculaire et cellulaire du neurone au travers de plus de 550 millions d'années d'évolution séparant les nématodes des mammifères. C. elegans possède un système nerveux simple formé de 302 neurones et d'environ 7000 synapses. Des outils génétiques puissants permettent d'isoler de nouveaux gènes et d'attribuer à des gènes connus de nouvelles fonctions dans la mise en place et le fonctionnement du réseau neuronal du nématode. Nous montrerons par quelques exemples comment les découvertes faites chez C. elegans ont pu être rapidement transposées à la biologie du système nerveux des mammifères.

Geroscience: Linking Aging to Chronic Disease

2014-11-01

Brian K. Kennedy , Shelley L. Berger , Anne Brunet +7 more

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Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans

1993-12-01

Bruce Wightman , Ilho Ha , Gary Ruvkun

The structure of the nervous system of the nematodeCaenorhabditis elegans

1986-11-12

JG White , Eileen Southgate , J. Nichol Thomson +1 more

The structure and connectivity of the nervous system of the nematode Caenorhabditis elegans has been deduced from reconstructions of electron micrographs of serial sections. The hermaphrodite nervous system has a … The structure and connectivity of the nervous system of the nematode Caenorhabditis elegans has been deduced from reconstructions of electron micrographs of serial sections. The hermaphrodite nervous system has a total complement of 302 neurons, which are arranged in an essentially invariant structure. Neurons with similar morphologies and connectivities have been grouped together into classes; there are 118 such classes. Neurons have simple morphologies with few, if any, branches. Processes from neurons run in defined positions within bundles of parallel processes, synaptic connections being made en passant. Process bundles are arranged longitudinally and circumferentially and are often adjacent to ridges of hypodermis. Neurons are generally highly locally connected, making synaptic connections with many of their neighbours. Muscle cells have arms that run out to process bundles containing motoneuron axons. Here they receive their synaptic input in defined regions along the surface of the bundles, where motoneuron axons reside. Most of the morphologically identifiable synaptic connections in a typical animal are described. These consist of about 5000 chemical synapses, 2000 neuromuscular junctions and 600 gap junctions.

The p66shc adaptor protein controls oxidative stress response and life span in mammals

1999-11-01

Enrica Migliaccio , Marco Giorgio , Simonetta Mele +5 more

Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans

2003-06-29

Coleen T. Murphy , Steven A. McCarroll , Cornelia I. Bargmann +5 more

Epigenetic Signatures of Obesity

2015-03-04

Susan E. Ozanne

Over the last 10 years the prevalence of obesity across the European continent has in general been rising. With the exception of a few countries where a levelling-off can be … Over the last 10 years the prevalence of obesity across the European continent has in general been rising. With the exception of a few countries where a levelling-off can be perceived, albeit at a high level, this upward trend seems likely to continue. However, considerable country to country variation is noticeable, with the proportion of people with obesity varying by 10% or more. This variation is intriguing and suggests the existence of different profiles of risk or protection factors operating in different countries. The identification of such protection factors could indicate suitable targets for interventions to help manage the obesity epidemic in Europe. This report is the output of a 2-day workshop on the 'Diversity of Obesity in Europe'. The workshop included 14 delegates from 12 different European countries. This report contains the contributions and discussions of the materials and viewpoints provided by these 14 experts; it is not the output of a single mind. However, such is the nature of scientific analysis regarding obesity that it is possible that a different set of 14 experts may have come to a different set of conclusions. Therefore the report should not be seen as a definitive statement of a stable situation. Rather it is a focus for discussion and comment, and a vehicle to drive forward further understanding and management of obesity in Europe.

Ageing as a risk factor for neurodegenerative disease

2019-09-09

Yujun Hou , Xiuli Dan , Mansi Babbar +4 more

Genome sequence of the nematode C-elegans: A platform for investigating biology

1998-12-11

Andrew Smith

Genome Sequence of the Nematode C. elegans : A Platform for Investigating Biology

1998-12-11

The 97-megabase genomic sequence of the nematode Caenorhabditis elegans reveals over 19,000 genes. More than 40 percent of the predicted protein products find significant matches in other organisms. There is … The 97-megabase genomic sequence of the nematode Caenorhabditis elegans reveals over 19,000 genes. More than 40 percent of the predicted protein products find significant matches in other organisms. There is a variety of repeated sequences, both local and dispersed. The distinctive distribution of some repeats and highly conserved genes provides evidence for a regional organization of the chromosomes.

Hallmarks of aging: An expanding universe

2023-01-01

Carlos López-Otı́n , Marı́a A. Blasco , Linda Partridge +2 more

Quinacrine and rimonabant prolong the life span of Caenorhabditis elegans

2025-06-25

Qianqian He , Shupan Guo , Aiyuan Zhou +3 more | GeroScience

Wounding induces preexisting multinucleated cells to survive and thrive as leader cells

2025-06-25

Yuta Takahashi , Kenji Matsuzawa , Junichi Ikenouchi | bioRxiv (Cold Spring Harbor Laboratory)

Epithelial wounds are repaired through collective cell migration, a process orchestrated by a small subset of leader cells at the wound edge. How these functionally distinct cells arise from an … Epithelial wounds are repaired through collective cell migration, a process orchestrated by a small subset of leader cells at the wound edge. How these functionally distinct cells arise from an apparently homogeneous population of epithelial cells remains unclear. Here, we show that injury to cultured epithelial sheets allows the survival of multinucleated cells that are otherwise eliminated under normal conditions. We reveal that multinucleated cells preexist prior to injury and extend protrusions toward the wound, eventually adopting leader-like behaviors. These findings identify multinucleated cells as a latent reservoir for leader cell emergence. Our work highlights the inherent heterogeneity of epithelial sheets and uncovers a previously unrecognized function of multinucleated cells during wound healing.

The roles of feedback loops in the Caenorhabditis elegans rhythmic forward locomotion

2025-06-25

Peng Zhao , Boyang Wang , Yi Rong +6 more | PLoS Computational Biology

Rhythmic behaviors are essential in biological systems, particularly in animal locomotion. The central pattern generator and sensory feedback loop mechanism have been instrumental in explaining many rhythmic locomotion patterns, however, … Rhythmic behaviors are essential in biological systems, particularly in animal locomotion. The central pattern generator and sensory feedback loop mechanism have been instrumental in explaining many rhythmic locomotion patterns, however, it is insufficient to account for the tunability and robustness of frequency and amplitude in certain oscillatory movements. This suggests the involvement of additional, less understood circuit mechanisms. This study employs calcium imaging and neuromechanical modelling to investigate the circuit mechanism responsible for sinusoidal forward locomotion in Caenorhabditis elegans . We demonstrate that the feedback loop circuit, consisting of motoneurons and muscles, could govern the generation of oscillations and regulate rhythmic forward movement. This circuit is composed of both negative and positive feedback loops, which together regulate the turnability and robustness of oscillations. The oscillatory behavior of C. elegans typically involves a rhythmic alternation of dorsoventral muscles. Our neuromechanical model of the functional oscillatory unit reveals that asymmetric inputs from interneurons to motoneurons, and asymmetric connections from motoneurons to muscles, are essential for this switching mechanism. Our findings suggest that, besides the established roles of existed oscillator mechanisms, circuits formed by both negative and positive feedback loops contribute to the generation and robust modulation of rhythmic behaviors.

Phylogenomic timetree-calibrated speciation clocks forCaenorhabditisnematodes reveal slow but disproportionate accumulation of post-zygotic reproductive isolation

2025-06-24

Daniel D. Fusca , M. Dall'Acqua , Santiago Sánchez‐Ramírez +1 more

Abstract Reproductive isolation and genomic divergence both accumulate over time in the formation and persistence of distinct biological species. The pace of “speciation clocks” quantified with pre-zygotic and post-zygotic reproductive … Abstract Reproductive isolation and genomic divergence both accumulate over time in the formation and persistence of distinct biological species. The pace of “speciation clocks” quantified with pre-zygotic and post-zygotic reproductive isolation, however, differs among taxa, with pre-zygotic isolation tending to evolve sooner in some but not all taxa. To address this issue in nematodes for the first time, here we infer the species tree and divergence times across the phylogeny of 51 species of Caenorhabditis . We incorporate several molecular evolutionary strategies in phylogenomic dating to account for complications in this group due to lack of fossil calibration, deep molecular divergence with synonymous-site saturation, and codon usage bias. By integrating divergence times with experimental data on pre- and post-zygotic reproductive isolation, we infer that post-zygotic isolation accumulates faster than pre-zygotic isolation in Caenorhabditis and that hybrid sterility evolves sooner than hybrid inviability. These findings are consistent with speciation being driven principally by intrinsic isolating barriers and the disproportionate fragility of germline developmental programs to disruption. We estimate that it takes approximately 50 million generations for intrinsic post-zygotic reproductive compatibility to be reduced by half, on average, between diverging pairs of Caenorhabditis . The protracted reproductive isolation clocks in Caenorhabditis may, in part, reflect the capacity to retain population genetic hyperdiversity, the incomplete sampling of global biodiversity, and as-yet uncharacterized incipient or cryptic species.

What are memories made of? A survey of neuroscientists on the structural basis of long-term memory

2025-06-24

Ariel Zeleznikow-Johnston , Emil F. Kendziorra , Andrew McKenzie | PLoS ONE

Despite the last decade’s development of optogenetic methods for artificially manipulating engrams, and subsequent claims that there is a consensus that memories are stored in ensembles of synaptic connections, it … Despite the last decade’s development of optogenetic methods for artificially manipulating engrams, and subsequent claims that there is a consensus that memories are stored in ensembles of synaptic connections, it remains unclear to what degree there truly is unanimity within the neuroscientific community about the neurophysiological basis of long-term memory. We surveyed 312 neuroscientists, comprising one cohort of experts on engram research and another of general neuroscientists, to assess this community’s views on how memories are stored. While 70.5% of participants agreed that long-term memories are primarily maintained by neuronal connectivity patterns and synaptic strengths, there was no clear consensus on which specific neurophysiological features or scales are critical for memory storage. Despite this, the median probability estimate that any long-term memories could potentially be extracted from a static snapshot of brain structure was around 40%, which was also the estimate for whether a successful whole brain emulation could theoretically be created from the structure of a preserved brain. When predicting the future feasibility of whole brain emulation, the median participant estimated this would be achieved for C. elegans around 2045, mice around 2065, and humans around 2125. Notably, neither research background nor expertise level significantly influenced views on whether memories could be extracted from brain structure alone. Our findings suggest that while most neuroscientists believe memories are stored in structural features of the brain, fundamental questions about the precise physical basis of memory storage remain unresolved. These findings have important implications for both theoretical neuroscience and the development of technologies aimed at preserving or extracting memory-related information.

Deneysel Beslenme Çalışmaları için Model Organizma: Drosophila melanogaster

2025-06-24

Selinay Taysi , Bülent Çeti̇n | Muş Alparslan Üniversitesi Fen Bilimleri Dergisi

İnsanlarda görülen sağlık problemlerinin teşhis ve tedavilerinde uygulanabilecek yöntemlerin geliştirilmesi için yapılması gereken çalışmalar insanlar üzerinde denenememektedir. Bu nedenle insana benzer özellik gösteren canlı türleri üzerinde çalışmalar sürdürülmektedir. Drosophila’da insana … İnsanlarda görülen sağlık problemlerinin teşhis ve tedavilerinde uygulanabilecek yöntemlerin geliştirilmesi için yapılması gereken çalışmalar insanlar üzerinde denenememektedir. Bu nedenle insana benzer özellik gösteren canlı türleri üzerinde çalışmalar sürdürülmektedir. Drosophila’da insana göstermiş olduğu benzerlik sayesinde biyolojik araştırmalar için tercih edilen bir model organizma olmuştur. Ancak yine de ‘’Bu kadar basit ve omurgasız bir organizma nasıl insan biyolojisi hakkında bilgi verir?’’ sorusu akılları karıştırmaktadır. İnsanlarda sağlık ve hastalıkların temelinde yer alan genler ve temel biyolojik süreçler Drosophila’da ilginç bir şekilde benzerlik göstermektedir. İnsan üzerinde hastalık yaptığı bilinen genlerin yüzde 70-75’inin Drosophila’da fonksiyonel ortologları bulunmaktadır. Bu sayede temel biyolojik mekanizmaları çözebilmek için Drosophila güçlü bir modeldir. Drosophila’nın insana benzer özellikler taşıması, yaşam döngüsünün kısa olması, embriyojenik gelişiminin kolay olması, endemik olmaması, düşük maliyetli olması ve en önemlisi etik sorun oluşturmaması gibi özellikleri model organizma olarak tercih edilmesinin en önemli nedenleridir. Drosophila’nın sağlamış olduğu bu avantajlar sayesinde genetik, fizyolojik, metabolik hastalıklar, biyolojik gelişim, sinir sistemi işlevleri, kök hücre biyolojisi, kanser ve nörodejeneratif hastalıklar gibi birçok hastalık Drosophila üzerinde modellenebilmektedir.

Developmental plasticity of hermaphrodite sperm production across environments in Caenorhabditis elegans

2025-06-24

Clotilde Gimond , Nausicaa Poullet , Anne Vielle +2 more | bioRxiv (Cold Spring Harbor Laboratory)

Abstract Many organisms show flexible resource allocation to adjust for optimal reproductive investment across different environments. How such reproductive plasticity occurs in hermaphroditic organisms—allocating resources to both oocytes and sperm—are … Abstract Many organisms show flexible resource allocation to adjust for optimal reproductive investment across different environments. How such reproductive plasticity occurs in hermaphroditic organisms—allocating resources to both oocytes and sperm—are central questions of sex allocation research. Self-fertilizing hermaphrodites of the androdioecious nematode Caenorhabditis elegans exhibit a sequential transition from spermatogenesis to oogenesis, so the extent of self-sperm production determines both fertilization onset and lifetime reproductive potential under selfing. Despite this key role, it remains largely unclear whether such sequential hermaphrodites flexibly adjust sperm production to optimize self-fertilization across different environments. Here we directly quantified plasticity in C. elegans hermaphrodite self-sperm production in diverse experimental environments. We found that: (a) Sperm production was developmentally plastic, but such changes did not consistently translate into changes in self-progeny number, suggesting C. elegans self-fecundity is often oocyte-limited rather than sperm-limited; (b) Contrary to expectations, plastically increased sperm production did not delay the onset of fertilization across various environments; (c) Subtle environmental challenges, such as mild dietary restriction, did not affect sperm production but had a significant impact on developmental time, age at reproductive maturity, and germline proliferation. This emphasizes the relative environmental insensitivity of sperm production compared to other reproductive traits in hermaphrodites. (d) Plasticity in sperm and germline traits varied by genetic background, with notable differences between the laboratory strain N2 and wild strains. These findings contribute to our understanding of reproductive plasticity in C. elegans and the developmental plasticity of sex allocation in sequential hermaphrodites.

Unpredictable disturbance and its effects on activity behavior and lifespan in Drosophila melanogaster

2025-06-23

Anabel S. X. Byars , Nicole C. Riddle | Biology Open

Animals exhibit natural movement patterns that are important for their survival and reproduction. Human disturbance can alter these movement patterns. In many natural settings, assessing the long-term impact of these … Animals exhibit natural movement patterns that are important for their survival and reproduction. Human disturbance can alter these movement patterns. In many natural settings, assessing the long-term impact of these altered movement patterns is difficult. Laboratory studies with model organisms may provide additional insight into the long- term effects of altered movement behaviors, such as those caused by human disturbance. Here, we investigate how unpredictable disturbance impacts animal activity and lifespan of Drosophila melanogaster. We selected four strains from the Drosophila Genetics Reference Panel (DGRP) to assess animals with different baseline activity levels. The unpredictable disturbance treatment was simulated using the TreadWheel to administer four randomized 30-minute disturbances daily. We found that both 5-day and 20-day disturbance treatments altered activity levels, but the response was dependent on sex, genotype, and age of the animals. While we detected altered animal activity in several groups, lifespan generally was not affected, with a few exceptions. Our results highlight the complexity involved in predicting individual responses to disturbance but suggest that long-term effects on lifespan are rare in response to short-term disturbance.

Enhanced whole-brain calcium imaging and cell identification in C. elegans reveal AWCOFF neuronal responses to 2-nonanone

2025-06-23

Yuto Endo , Ryoga Suzuki , Taihei Ito +3 more | Journal of Biosciences

The chromatin remodeler LET-418/Mi-2 regulates the intracellular pathogen response in the C. elegans intestine

2025-06-22

Shweta Rajopadhye , Vladimir Lažetić , David Rodríguez-Crespo +3 more | bioRxiv (Cold Spring Harbor Laboratory)

Chromatin remodeling provides essential transcriptional regulation for all biological processes. In Caenorhabditis elegans , the chromatin remodeler LET-418, a homolog of the human Mi-2 protein, plays a critical role in … Chromatin remodeling provides essential transcriptional regulation for all biological processes. In Caenorhabditis elegans , the chromatin remodeler LET-418, a homolog of the human Mi-2 protein, plays a critical role in regulating development, organogenesis, tissue maintenance, stress resistance and lifespan. LET-418 is part of several chromatin remodeling complexes and contributes significantly to the balance between growth and defense mechanisms, yet its target genes remain unclear. Using DNA methylation profiling, we identified genomic binding sites and associated target genes of LET-418 and its MEC-complex-specific interactor MEP-1 in the intestine. Consistent with their presence in the same complex, the two proteins shared more than half of their target genes. Functional analysis revealed that LET-418 and MEP-1 target genes are highly active in the intestine and are involved in repressing innate immune responses, including the intracellular pathogen response (IPR). Consistently, in let-418 mutants, IPR-induced genes, such as pals-5 or pals-2 are strongly upregulated, in a manner dependent on ZIP-1, a major transcription factor for IPR. Additionally, we found pathogen levels of the natural intracellular intestinal pathogen Nematocida parisii significantly reduced in let-418 mutants, supporting the observation of increased IPR in this mutant. Altogether, these findings reveal a crucial role for LET-418 as a modulator of the IPR, aligning with its role in maintaining the balance between development and defense.

Five new Caenorhabditis species from Indonesia provide exceptions to Haldane's rule and partial fertility of interspecific hybrids

2025-06-21

M. P. Devi , Elkana Haryoso , Emha Ilhami Rais +7 more | G3 Genes Genomes Genetics

Abstract Given the interest in the biogeography and diversity of the Caenorhabditis genus, we established a collection of these nematodes from field surveys on four Indonesian islands. We isolated over … Abstract Given the interest in the biogeography and diversity of the Caenorhabditis genus, we established a collection of these nematodes from field surveys on four Indonesian islands. We isolated over 60 Caenorhabditis strains belonging to ten species. Five species were previously known from other locations: C. briggsae, which was predominant, C. tropicalis, C. nigoni, C. brenneri and C. elegans. The five other species are new discoveries for science, and we describe them here as Caenorhabditis indonesiana, Caenorhabditis malinoi, Caenorhabditis ceno, Caenorhabditis brawijaya and Caenorhabditis ubi. RNA sequence analysis of 1,861 orthologous genes placed all species from Indonesia in the Elegans group of Caenorhabditis species. Four of the new species belong to a Sinica subclade of species so far only found in an East Asia-Indo-Pacific world region. The fifth new species, C. indonesiana, appears as the sister of the C. tropicalis-C. wallacei pair, both also found in Indonesia. The present findings are thus consistent with diversification in the Elegans group having occurred in this world region. Crosses between closely related species showed counterexamples to Haldane's “rule”: for several pairs of species, in one cross direction we only found hybrid males. In addition, we found a pair of species that could partially interbreed: Caenorhabditis ubi (East Java) with C. sp. 41 (Solomon islands), with the hybrid males in one cross direction being fertile. Such closely related species pairs are good models for genetic studies of incompatibilities arising during speciation.

Low-Temperature Stress-Induced Hepatic Injury in Darkbarbel Catfish (Pelteobagrus vachelli): Mediated by Gut–Liver Axis Dysregulation

2025-06-21

Amei Liu , Guoqing Duan , Libo Yang +3 more | Antioxidants

Low-temperature stress serves as a critical abiotic stressor that severely restricts fish survival, biogeographic distribution, and aquaculture productivity. Pelteobagrus vachelli, an economically significant freshwater fish species, displays marked sensitivity to … Low-temperature stress serves as a critical abiotic stressor that severely restricts fish survival, biogeographic distribution, and aquaculture productivity. Pelteobagrus vachelli, an economically significant freshwater fish species, displays marked sensitivity to low-temperature stress; however, its molecular adaptive mechanisms remain poorly characterized. In this study, we systematically investigated hepatic and intestinal cold stress responses in P. vachelli through a 7-day acute low-temperature exposure trial (6 °C and 11 °C), integrating histopathological examination, physiological–biochemical assays, metabolomics, and 16S rRNA sequencing. Histopathological observations revealed pronounced hepatic vacuolar degeneration, nuclear dissolution, and enhanced inflammatory cell infiltration under low-temperature conditions. Concurrently, immune-related enzymatic activities—including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (APK)—were significantly elevated. Furthermore, substantial perturbations in antioxidant defense systems were detected, as indicated by altered superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, alongside malondialdehyde (MDA) accumulation. Metabolomic profiling identified 539 differentially abundant metabolites, with pathway enrichment analysis highlighting marked alterations in FoxO signaling, amino acid metabolism, glycerophospholipid metabolism, ABC transporter, and Purine metabolism. Gut microbiome sequencing demonstrated cold-induced structural dysbiosis within the intestinal microbiota. Correlation analyses revealed robust linkages between hepatic injury biomarkers/metabolites and specific intestinal microbial taxa. Collectively, this study delineates the interplay between hepatic metabolic reprogramming and gut microbiota dysbiosis during cold adaptation in P. vachelli, establishing a theoretical framework for developing gut–liver axis-targeted strategies to augment cold tolerance in aquatic species.

In Vivo Imaging of Neural Activity in Unanesthetized Drosophila Adult Flies

2025-06-20

Prachi Shah , Isaac Cervantes-Sandoval | Journal of Visualized Experiments

Regulation of MORC-1 is key to the CSR-1–mediated germline gene licensing mechanism in C. elegans

2025-06-20

Jessica A. Kirshner , Colette L. Picard , Natasha E. Weiser +7 more | Science Advances

The Argonaute CSR-1 is essential for germline development in C. elegans . Loss of CSR-1 leads to the down-regulation of thousands of germline-expressed genes, supporting a model in which CSR-1 … The Argonaute CSR-1 is essential for germline development in C. elegans . Loss of CSR-1 leads to the down-regulation of thousands of germline-expressed genes, supporting a model in which CSR-1 “licenses” gene expression via a poorly understood mechanism. In contrast, a small subset of genes is up-regulated in csr-1 mutants, including morc-1 , which encodes a conserved GHKL-type ATPase. We show that morc-1 is overexpressed in csr-1 mutants and accumulates over CSR-1 licensed targets, coinciding with aberrant gain of H3K9me3, reduced H3K36me3, and transcriptional repression. Notably, loss of morc-1 fully rescues these chromatin defects and partially restores gene expression and fertility in csr-1 mutants. Conversely, ectopic overexpression of MORC-1 in the wild-type germ line is sufficient to repress CSR-1 licensed targets and severely compromise fertility. These findings support a model in which CSR-1 prevents MORC-1 overexpression and consequent misregulation of CSR-1 licensed genes.

Lineage-resolved analysis of embryonic gene expression evolution in C. elegans and C. briggsae

2025-06-19

Christopher R. L. Large , R. C. Khanal , LaDeana Hillier +5 more | Science

The constraints that govern the evolution of gene expression patterns across development remain unclear. Single-cell RNA sequencing can detail these constraints by systematically profiling homologous cells. The conserved invariant embryonic … The constraints that govern the evolution of gene expression patterns across development remain unclear. Single-cell RNA sequencing can detail these constraints by systematically profiling homologous cells. The conserved invariant embryonic lineage of Caenorhabditis elegans and C. briggsae makes them ideal for comparing cell type gene expression across evolution. Measuring the spatiotemporal divergence of gene expression across embryogenesis, we find a high level of similarity in gene expression programs between species despite tens of millions of years of evolutionary divergence. Nonetheless, thousands of genes show divergence in their cell type specific expression patterns, with enrichment for functions in environmental response and behavior. Neuronal cell types show higher divergence than others such as the intestine and germline. This work identifies likely constraints on the evolution of developmental gene expression.

Editorial: Survival strategies: cellular responses to stress and damage

2025-06-19

Bhawana Bissa , Aurore Claude‐Taupin , Pavel Ivanov +2 more | Frontiers in Cell and Developmental Biology

Rapamycin, Not Metformin, Mirrors Dietary Restriction‐Driven Lifespan Extension in Vertebrates: A Meta‐Analysis

2025-06-18

Edward Ivimey‐Cook , Zahida Sultanova , Alexei A. Maklakov | Aging Cell

ABSTRACT Dietary restriction (DR) robustly increases lifespan across taxa. However, in humans, long‐term DR is difficult to maintain, leading to the search for compounds that regulate metabolism and increase lifespan … ABSTRACT Dietary restriction (DR) robustly increases lifespan across taxa. However, in humans, long‐term DR is difficult to maintain, leading to the search for compounds that regulate metabolism and increase lifespan without reducing caloric intake. The magnitude of lifespan extension from two such compounds, rapamycin and metformin, remains inconclusive, particularly in vertebrates. Here, we conducted a meta‐analysis comparing lifespan extension conferred by rapamycin and metformin to DR‐mediated lifespan extension across vertebrates. We assessed whether these effects were sex‐ and, when considering DR, treatment‐specific. In total, we analysed 911 effect sizes from 167 papers covering eight different vertebrate species. We find that DR robustly extends lifespan across log‐response means and medians and, importantly, rapamycin—but not metformin—produced a significant lifespan extension. We also observed no consistent effect of sex across all treatments and log‐response measures. Furthermore, we found that the effect of DR was robust to differences in the type of DR methodology used. However, high heterogeneity and significant publication bias influenced results across all treatments. Additionally, results were sensitive to how lifespan was reported, although some consistent patterns still emerged. Overall, this study suggests that rapamycin and DR confer comparable lifespan extension across a broad range of vertebrates.

Photo-aged polylactic acid microplastics causes severe transgenerational decline in reproductive capacity in C. elegans: Insight into activation of DNA damage checkpoints affected by multiple germline histone methyltransferases

2025-06-18

Jingwei Wu , Yuting Shao , Xin Hua +2 more | Environmental Pollution

Heat shock proteins function as signaling molecules to mediate neuron–glia communication in C. elegans during aging

2025-06-18

Jieyu Wu , Victoria R. Yarmey , Olivia Jiaming Yang +3 more | Nature Neuroscience

Measuring Associative Learning in Chemotaxis of the Nematode Caenorhabditis elegans

2025-06-17

Daniel-Cosmin Marcu , Evelyn Berthold , Karl Emanuel Busch | Journal of Visualized Experiments

Lysergic Acid Diethylamide extends lifespan in Caenorhabditis elegans

2025-06-17

Beatriz de Sá Carrilho , Aline Teixeira Duarte-Silva , Ariana Moura Krettli Sant Anna +5 more | bioRxiv (Cold Spring Harbor Laboratory)

Aging is modulated by nutrient-sensing pathways that integrate metabolic and hormonal cues to regulate growth, stress resilience, and lifespan. Caloric restriction (CR), a well-established intervention, extends longevity in diverse species … Aging is modulated by nutrient-sensing pathways that integrate metabolic and hormonal cues to regulate growth, stress resilience, and lifespan. Caloric restriction (CR), a well-established intervention, extends longevity in diverse species primarily through inhibition of the TOR signaling pathway. Lysergic acid diethylamide (LSD), a classic serotonergic psychedelic with emerging therapeutic applications, remains largely unexplored in the context of aging. Here, we show that LSD treatment significantly extends lifespan in Caenorhabditis elegans and reduces age-associated lipofuscin accumulation, indicative of delayed cellular aging. LSD reproduces several CR-like phenotypes, including decreased reproductive output and increased nuclear localization of the transcription factor PHA-4/FOXA, without affecting food intake. Moreover, LSD treatment reduces lipid stores and downregulates global protein synthesis, both hallmark signatures of TOR inhibition. These findings establish LSD as a modulator of evolutionarily conserved longevity pathways and suggest that psychedelic signaling can mimic a caloric restriction-like metabolic state, paving the way for the development of novel geroprotective strategies.

Broad epigenetic shifts in the aging Drosophila retina contribute to its altered rhythmic transcriptome.

2025-06-17

Sarah McGovern , Gaoyuan Meng , Makayla M. Marlin +2 more | bioRxiv (Cold Spring Harbor Laboratory)

ABSTRACT Alterations in biological rhythms are a common feature of aging, and disruption of circadian rhythms can exacerbate age-associated pathologies. The retina is critical for detecting light for both vision … ABSTRACT Alterations in biological rhythms are a common feature of aging, and disruption of circadian rhythms can exacerbate age-associated pathologies. The retina is critical for detecting light for both vision and for transmitting time-of-day information to the brain, synchronizing rhythms throughout the body. Disruption of circadian rhythms by manipulating the molecular clock leads to premature retinal degeneration in flies and mice, and gene expression rhythms are disrupted in models of age-associated ocular disease. Despite this, it is unknown how or why the gene expression rhythms of the retina change with age. Here, we show that ∼70% of the Drosophila transcriptome is rhythmically expressed throughout the diurnal cycle, with ∼40% of genes showing altered rhythms with age. These transcriptome-wide changes in aging photoreceptors are accompanied by shifts in the rhythmic patterns of RNA Polymerase II (Pol II) occupancy, histone H3 lysine 4 (H3K4) methylation, and chromatin accessibility, without major changes in occupancy of the circadian clock transcription factors Clock (Clk) and Cycle (Cyc). Instead, aging decreases genome-wide levels of several different histone methyl marks including H3K4 methylation, whose relative levels across the day correlate with the phase of rhythmic gene expression. Moreover, individual knockdown of the three H3K4 methyltransferases in young photoreceptors results in massive disruptions to rhythmic gene expression that resemble those observed during aging. We conclude that there are broad epigenetic shifts in the aging retina, including decreased histone methylation, that contribute to changes in biological rhythms even in the presence of a robust molecular circadian clock.

Creatine Exposure in Caenorhabditis elegans Induces Physiological and Morphological Changes without Metabolic Conversion to Creatinine: A Novel HPLC Analysis

2025-06-17

Lance Kuo-Esser , Kylie Lawson , N. W. King +7 more | ACS Omega

Proximity Labeling of NIMA Kinase Complex Components in C. elegans

2025-06-17

David S. Fay , Boopathi Balasubramaniam , Sean Harrington +1 more | bioRxiv (Cold Spring Harbor Laboratory)

Proximity labeling has emerged as a powerful approach for identifying protein–protein interactions within living systems, particularly those involving weak or transient associations. Here, we present a comprehensive proximity labeling study … Proximity labeling has emerged as a powerful approach for identifying protein–protein interactions within living systems, particularly those involving weak or transient associations. Here, we present a comprehensive proximity labeling study of five conserved Caenorhabditis elegans proteins—NEKL-2, NEKL-3, MLT-2, MLT-3, and MLT-4—that form two NEKL–MLT kinase–scaffold subcomplexes involved in membrane trafficking and actin regulation. Using endogenously expressed TurboID fusions and a data-independent acquisition (DIA) mass spectrometry (MS) pipeline, we profiled NEKL–MLT interactomes across 23 experiments, including several methodological variations, applying stringent controls and filtering strategies. By analyzing and comparing experimental outcomes, we develop a set of intuitive quantitative metrics to assess experimental outcomes and quality. We demonstrate that DIA-based workflows produce sensitive physiologically relevant findings, even in the presence of experimental noise and variability across biological replicates. Our approach is validated through the identification of known NEKL–MLT binding partners and conserved genetic suppressors of nekl–mlt mutant phenotypes. Gene ontology enrichment further supports the involvement of newly identified NEKL–MLT interactors in processes including membrane trafficking, cytoskeletal regulation, and cell adhesion. Additionally, several novel proximate interactors were functionally validated using genetic assays. Our findings underscore the utility of DIA-MS in proximity labeling applications and highlight the value of incorporating internal controls, quantitative metrics, and biological validation to enhance confidence in candidate interactors. Overall, this study provides a scalable, organismal-level strategy for probing endogenous protein networks and offers practical guidelines for proximity labeling in multicellular systems.

The Applications of Caenorhabditis elegans Worm in Neuroscience: A Review Study

2025-06-16

S Davari , Alireza Ghahari , Erfan Kamali Far | International Journal of Medical Parasitology and Epidemiology Sciences

Caenorhabditis elegans is a small, free-living nematode that has become a crucial model organism in various fields of biological research, especially in neuroscience. This transparent roundworm is particularly useful in … Caenorhabditis elegans is a small, free-living nematode that has become a crucial model organism in various fields of biological research, especially in neuroscience. This transparent roundworm is particularly useful in studying the genetics, development, and function of the nervous system. With its simple nervous system composed of only 302 neurons, C. elegans provides an ideal platform for investigating the molecular mechanisms underlying neurological diseases and behaviors.

HealthAge: evaluation of intrinsic capacity changes in humans, mice, and killifish to explore the biology of aging

2025-06-16

Sophie Guyonnet , Claudie Hooper , Heike A. Bischoff‐Ferrari +5 more | GeroScience

Abstract HealthAge was devised by a conglomerate of research groups in Toulouse, France, with the combined goal of narrowing the lifespan-healthspan gap through novel translational bench-to-bedside research studies. HealthAge comprises … Abstract HealthAge was devised by a conglomerate of research groups in Toulouse, France, with the combined goal of narrowing the lifespan-healthspan gap through novel translational bench-to-bedside research studies. HealthAge comprises the “INStitute for Prevention” “healthy aging” and “medicine Rejuvenative” (INSPIRE) human translational, outbred SWISS mice and African turquoise killifish (GRZ strain) cohorts in which aging is studied based on the concept of intrinsic capacity (IC). In this narrative review, we describe the three INSPIRE aging models (human cohort, n = 1109, age range 20 –102 years old with mean age ± standard deviation, 62.4 ± 19.0 years and 61.9% female; outbred SWISS mice, n = 1576 and African Turquoise killifish, n = 300) and explain how IC is assessed at the clinical (in humans) and biological level over time. HealthAge strives to elucidate the underlying biology of IC and to identify biomarkers of IC declines and novel gero-therapeutics using the clinical and biological data and biospecimens collected prospectively in the three species. The data sharing policy will foster scientific discovery through new multi-disciplinary collaborations. Thus, HealthAge will promote healthy aging using a unique translational platform based on IC phenotyping with the ultimate goal of preventing loss of human independence and alleviating health costs associated with an aging population.

Non-autonomy of age-related morphological changes in the C. elegans germline stem cell niche

2025-06-16

N. Gupta , Mia Sinks , E. Jane Albert Hubbard | bioRxiv (Cold Spring Harbor Laboratory)

A decline in tissue renewal and repair due to changes in tissue stem cells is a hallmark of aging. Many stem cell pools are maintained by interaction with morphologically complex … A decline in tissue renewal and repair due to changes in tissue stem cells is a hallmark of aging. Many stem cell pools are maintained by interaction with morphologically complex local niches. Using the C. elegans hermaphrodite germline stem cell system, we analyzed age-related changes in the morphology of the niche, the distal tip cell (DTC), and identified a molecular mechanism that promotes a subset of these changes. We found that a long-lived daf-2 mutant exhibits a daf-16 -dependent decline in number and length of long DTC processes. Surprisingly, the tissue requirement for daf-16(+) is non-autonomous and is independent of the longevity requirement: daf-16(+) in body wall muscle is both necessary and sufficient. We also determined that pre-formed DTC processes deteriorate prematurely when the underlying germline differentiates. We propose a reciprocal DTC-germline interaction model and speculate a mechanism by which reducing daf-2 activity prevents stem cell exhaustion. These studies establish the C. elegans DTC as a powerful in vivo model for understanding age-related changes in cellular morphology and their consequences in stem cell systems.

An insulin-sensitive Drosophila insulin-like receptor mutant remodels methionine metabolism to extend lifespan

2025-06-16

Marc Tatar , Wenjing Zheng , Shweta Yadav +5 more | PLoS Genetics

Insulin/insulin growth factor signaling is a conserved pathway that regulates lifespan across many species. Multiple mechanisms are proposed for how this altered signaling slows aging. To elaborate these causes, we … Insulin/insulin growth factor signaling is a conserved pathway that regulates lifespan across many species. Multiple mechanisms are proposed for how this altered signaling slows aging. To elaborate these causes, we recently developed a series of Drosophila insulin-like receptor ( dInr ) mutants with single amino acid substitutions that extend lifespan but differentially affect insulin sensitivity, growth and reproduction. Transheterozygotes of canonical dInr mutants (Type I) extend longevity and are insulin-resistant, small and weakly fecund. In contrast, a dominant mutation ( dInr 353 , Type II) within the Kinase Insert Domain (KID) robustly extends longevity but is insulin-sensitive, full-sized, and highly fecund. We applied transcriptome and metabolome analyses to explore how dInr 353 slows aging without insulin resistance. Type I and II mutants overlap in many pathways but also produce distinct transcriptomic profiles that include differences in innate immune and reproductive functions. In metabolomic analyses, the KID mutant dInr 353 reprograms methionine metabolism in a way that phenocopies dietary methionine restriction, in contrast to canonical mutants which are characterized by upregulation of the transsulfuration pathway. Because abrogation of S-adenosylhomocysteine hydrolase blocks the longevity benefit conferred by dInr 353 , we conclude the methionine cycle reprogramming of Type II is sufficient to slow aging. Metabolomic analysis further revealed the Type II mutant is metabolically flexible: unlike aged wildtype, aged dInr 353 adults can reroute methionine toward the transsulfuration pathway, while Type I mutant flies upregulate the transsulfuration pathway continuously from young age. Altered insulin/insulin growth factor signaling has the potential to slow aging without the complications of insulin resistance by modulating methionine cycle dynamics.

Metformin modulates the unfolded protein responses, altering lifespan and health-promoting effects in UPR-activated worms

2025-06-16

Jun Tan , Chutipong Chiamkunakorn , Kanpapat Boonchuay +3 more | PLoS ONE

Metformin has been demonstrated to extend lifespan in various model organisms, and its molecular effects are observed in the cytoplasm and multiple organelles, including mitochondria. However, its association with the … Metformin has been demonstrated to extend lifespan in various model organisms, and its molecular effects are observed in the cytoplasm and multiple organelles, including mitochondria. However, its association with the unfolded protein response (UPR) and its impact on stress resistance and locomotion remain uncertain. In this study, metformin was found to exert differential influences on both UPR mt and UPR er . The correlation between metformin’s lifespan-mediating effect and its interaction with UPRs was also inconsistent. We identified a metformin-mediated lifespan extension in wild-type C. elegans and in UPR mt -activated tomm-22 and cco-1 RNAi worms. Metformin suppressed the UPR mt without compromising the lifespan extension observed in tomm-22 worms. Conversely, metformin did not affect the UPR mt but extended the lifespan of long-lived cco-1 RNAi worms. Furthermore, we investigated the effects of metformin on UPR er -activated nematodes. We observed that metformin exhibited a slight increase in the UPR er in mdt-15 RNAi worms and failed to induce lifespan extension. Surprisingly, metformin appeared to mediate lifespan extension in tmem-131 RNAi worms while suppressing the UPR er . Notably, the correlation between thermotolerance, oxidative stress resistance, and the lifespan effects of metformin in UPR-activated worms was inconsistent. Activation of UPRs, but not metformin treatment, enhanced the locomotor phenotype of these worms.

When leaders fail: Exploring the role of dysfunctional leader cells in autoimmune disease pathogenesis

2025-06-16

Falah Hasan Obayes Al-Khikani | Bangabandhu Sheikh Mujib Medical University Journal

Not available Not available

Metabolic analysis of sarcopenic muscle identifies positive modulators of longevity and healthspan in C. elegans

2025-06-14

Steffi M Jonk , Alan Nicol , Vicki Chrysostomou +7 more | Redox Biology

Assessment of the Food Value of Trametes elegans Before and After Fermentation

2025-06-14

Victor Olusegun Oyetayo , JT Ayodele | Asian Journal of Biological Sciences

Reply to Ferraro et al.: Breed-and-feed reflects inevitable trade-offs between individual longevity and population sustainability

2025-06-13

Marcus Clauß , Marco Roller , Mads F. Bertelsen +7 more | Proceedings of the National Academy of Sciences

Heat‐induced effects on longevity and early fecundity reveal differences between the sibling species Drosophila buzzatii and Drosophila koepferae

2025-06-13

Federico H. Gómez , Pablo Sambucetti , Fabian M. Norry | Entomologia Experimentalis et Applicata

Abstract Sub‐lethal exposure to an elevated temperature can improve some traits, including longevity and/or early fecundity (EF), a phenomenon known as hormesis. Here, sub‐lethal and repeated exposures to heat were … Abstract Sub‐lethal exposure to an elevated temperature can improve some traits, including longevity and/or early fecundity (EF), a phenomenon known as hormesis. Here, sub‐lethal and repeated exposures to heat were applied in two sibling species, Drosophila buzzatii (Patterson and Wheeler) and Drosophila koepferae (Fontdevila and Wasserman) (both Diptera: Drosophilidae), to assess any possible heat‐induced effects on longevity and EF at benign temperature. In addition, heat‐knockdown resistance was measured in each species. As in previous studies, D. koepferae was found to be a short‐lived species as compared to other Drosophila species, including D. buzzatii . Heat‐knockdown resistance in females was higher in D. buzzatii than in D. koepferae , but no significant difference between species was found in males in a mixed‐sex environment. Hormesis in longevity was substantial in D. buzzatii , but no hormesis was found in the longevity of D. koepferae . Relative early fecundity (REF) strongly increased due to heat stress in females of D. koepferae , whereas no changes were found for this trait in D. buzzatii . These results show that the hormetic response to repeated exposures to heat can differ between very closely related species that share the same thermal environments in sympatric arid populations where there is no place to hide, differentially affecting traits of the well‐known trade‐off between longevity and EF. Taken together, the results from this and previous studies suggest that, in contrast to D. buzzatii , the short‐lived D. koepferae appears to be the fly that not always can extend its longevity by exposures to an elevated but sub‐lethal temperature. Interestingly, in contrast to longevity, EF in D. koepferae and not in D. buzzatii was found to increase due to the exposure to elevated temperature, revealing differences between these sibling species.

Mitochondrial sirtuin 4 shapes the intestinal microbiota of Drosophila by controlling lysozyme expression

2025-06-13

Mirjam Knop , Christian Treitz , Stina Bettendorf +7 more | Animal Microbiome