Getting rid of senescent cells for healthy aging

Long Long Life Éliminer les cellules sénescentes pour vieillir en bonne santé

Getting rid of senescent cells for healthy aging

Cell senescence, one of the 9 causes of aging described in The Hallmarks of Aging [1], is defined as a state of cell cycle arrest along with phenotypic changes [1,2]. This process is induced by various stresses like DNA damage, telomere shortening or inflammation. The number of senescent cells increases with age in multiple tissues, during pathologies or following chemotherapy [2]. Senescence is thought to cause tissue and organ dysfunction with age. The increased number of senescent cells during aging can be explained by the decrease in their clearance and, possibly, by their increased natural generation, although the last cause is not accepted by all. In a recent study published in Nature [3], a team of scientists has shown that a rise of the abundance of senescent cells leads to an increasing number of physical dysfunctions in young and old mice, and that the suppression of these cells is associated with an extended healthy lifespan in mice.

Long Long Life getting rid of senescent cell for healthy aging

Indeed, in their experiments, scientists induced physical dysfunctions in young mice after transplanting senescent cells. These results were obtained with a small number of senescent cells, and an even smaller number of these cells was sufficient in elderly mice to contribute to loss of physical function and decreased survival [3]. For researchers, these results attest of the impact of senescent cells on physical dysfunctions observed with age and of their part in the lifespan of mice [3]. Thus, senescent cells could become a therapeutic target for improving healthy lifespan.

Which therapeutics against the senescent cells ?

Recently a group of compounds called senolytics, drugs that specifically target and eliminate senescent cells, have been developed. Among them, quercetin and dasatinib were the first to be studied [4]. The same team of researchers had previously shown that these two compounds were capable of eliminating human and murine senescent cells [4]. In their new study, they sought to verify these observations by testing the effect of the same mixture of senolytics on human adipose tissue. Obtained from obese people, these tissues show a strong accumulation of senescent cells [3]. These cells release a variety of factors such as pro-inflammatory cytokines and chemokines, which contribute to the physical dysfunction of tissues and organs during aging. The findings of these experiments showed that administration of senolytics was associated with a decrease in the number of senescent cells as well as a decrease of the cytokine secretion in human tissues, emphasizing the importance of signalling and communication between cells in aging processes[3]. Finally, their study also found that eliminating senescent cells attenuated physical dysfunctions and increased the healthy life span of mice, even the elderly [3].

This new study on senescent cells provides evidence of their involvement in the physical dysfunctions that occur with the aging of mice and leads to a reduction in their lifespan. These cells can be targeted by a new category of drugs that eliminate them, senolytics, thus reducing physical dysfunctions. According to the study, eliminating the load of senescent cells found during aging would also extend the lifespan. Senolytics could potentially become a new class of active compounds that fight aging and improve the healthy lifespan of older people.

Anne Fischer

Long Long Life Anne Fischer icon

Author

Auteur

Anne is studying medicine science at the Institute of Pharmaceutical and Biological Science in Lyon and she has graduated with a Bachelor’s degree in molecular and cellular biology at the University of Strasbourg.

More about the Long Long Life team

Anne étudie les sciences du médicament à l’Institut des Sciences Pharmaceutiques et Biologiques de Lyon. Elle est titulaire d’une licence en biologie moléculaire et cellulaire de l’Université de Strasbourg.

En savoir plus sur l’équipe de Long Long Life

References :

[1] Carlos Lopez-Otin, Maria A. Blasco, Linda Partridge, Manuel Serrano and Guido Kroemer, The Hallmarks of Aging, Cell 153, June 6, 2013, 1194-1217.

[2] Salama et al. Cellular senescence and its effector programs, GENES & DEVELOPMENT 28:99–114.

[3] Ming Xu, Tamar Pirtskhalava, Joshua N. Farr, Bettina M. Weigand, Allyson K. Palmer, Megan M. Weivoda, Christina L. Inman, Mikolaj B. Ogrodnik, Christine M. Hachfeld, Daniel G. Fraser, Jennifer L. Onken, Kurt O. Johnson, Grace C. Verzosa, Larissa G. P. Langhi, Moritz Weigl, Nino Giorgadze, Nathan K. LeBrasseur, Jordan D. Miller, Diana Jurk, Ravinder J. Singh, David B. Allison, Keisuke Ejima, Gene B. Hubbard, Yuji Ikeno, Hajrunisa Cubro, Vesna D. Garovic, Xiaonan Hou, S. John Weroha, Paul D. Robbins, Laura J. Niedernhofer, Sundeep Khosla, Tamara Tchkonia and James L. Kirkland, Senolytics improve physical function and increase lifespan in old age, Nature medicine, https://doi.org/10.1038/s41591-018-0092-9

[4] Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14(4):644-658

Indolepropionamide beats all records

Indolepropionamide pill - long long life anti aging transhumanism longevity supplement

Fact sheet

Indolepropionamide : a new hope

Introducing new molecules of interest is also keeping you informed of promising advances in anti-aging research. With indolepropionamide, despite few studies, we are dealing with THE anti-aging molecule, as when administrated, it increases up to 300% the lifespan of the models used.

Interest
Efficiency
Availibity

Long Long Life does not sell any of these products. We believe this to be the price of freedom.

Since we have no financial interest in this, we can tell you the whole truth on the treatments being developped to fight against aging, and give you the best information possible.

A single study, multiple effects

There is only one published study on indolepropionamide and its effect on aging [1]. The team used rotifers, a micro-organism model, for which they observed an increase in lifespan never equaled by other molecules. This longevity was accompanied by better cell repair and increased resistance to injury.

It would seem that this effect is due to a drastic improvement in mitochondrial function accompanied by a significant reduction in the formation of free radicals. The amazing antioxidant properties of indolepropionamide are linked to its structure, very close to that of melatonin, and to its ability to interact with the oxidative phosphorylation chain of mitochondria. It would indeed seem that indolepropionamide is capable of stabilizing mitochondrial energy metabolism by binding to the complex I of the respiratory chain, thus causing a decrease in oxidant production. One of its close cousins, 3-indolepropionic acid, is currently undergoing clinical trials to fight Alzheimer’s disease. It has indeed the same type of properties, because of their homologies of structure, both close to melatonin.

Although new studies are needed, particularly in mammals, indolepropionamide is an extremely promising molecule and its derivatives already seem to offer good prospects, particularly in the fight against neurodegenerative diseases. Moreover, indolepropionamide is an amphiphilic molecule, thus passing as well the cellular membranes as the aqueous structures, and its bioavailability is excellent.

  • Number publications : 1
  • Availability : not available for sale
  • Route : intravenous
  • Dosage : to be defined

No toxicity has been reported to date but further studies are needed.

[1] Poeggeler B, Sambamurti K, Siedlak SL, Perry G, Smith MA, Pappolla MA. A Novel Endogenous Indole Protects Rodent Mitochondria and Extends Rotifer Lifespan. Blagosklonny MV, ed. PLoS ONE. 2010;5(4):e10206

DISCLAIMER

The information on the present website does not constitute either directly or indirectly any medical advice. The provided information is intended to inform and is in no way a substitute for the direct relationship between a patient and a health professional. Under no circumstances the information on the website are likely to make up for consulting, visiting and diagnosis by a licensed healthcare professional. Said information should not be interpreted as ensuring the promotion any some molecules or medical products.

Long Long Life will not be held liable for any action or decision-making in relation to the information on this website.

Long Long Life does not guarantee by any means any result following the implementation of the published information on the website herein.

Self-medication can be dangerous for your health, please seek medical advice before starting any treatment.

Dr. Marion Tible

Marion Tible Long Long Life

Author/Reviewer

Auteure/Relectrice

Marion Tible has a PhD in cellular biology and physiopathology. Formerly a researcher in thematics varying from cardiology to neurodegenerative diseases, she is now part of Long Long Life team and is involved in scientific writing and anti-aging research.

More about the Long Long Life team

Marion Tible est docteur en biologie cellulaire et physiopathologie. Ancienne chercheuse dans des thématiques oscillant de la cardiologie aux maladies neurodégénératives, elle est aujourd’hui impliquée au sein de Long Long Life pour la rédaction scientifique et la recherche contre le vieillissement.

En savoir plus sur l’équipe de Long Long Life

Understand aging with genomics, proteomics, and all things -omics!

omics
Artificial Intelligence, network connection technology

Understand aging with genomics, proteomics, and all things -omics!

“Omics” approaches are a set of analytical tools to explore the functions of our bodies. The best known ones are genomics, transcriptomics, proteomics and metabolomics, but newer branches have recently emerged, such as lipidomics, glycomics or nutriomics.

Genomics correspond to the study of the genome, i.e. everything that concerns DNA modifications, mutations, expression… Transcriptomics take a look at the next stage, everything in the order of the transcriptome, messenger RNAs coding for our proteins, non-coding RNAs, transcription regulation… For proteomics, it is still the next step, namely the study of proteins, their translation, folding and modification. Finally, metabolomics is the analysis of chemical factors regulating inter- and intracellular interactions, also called metabolites.

New types of analysis include the study of lipids (lipidomics), carbohydrates (glycomics) and nutrition and its impact on our bodies (nutriomics). These are fields as vast as the first and which constitute the future of research in “omics” approaches.

Fight aging with multifactorial “-omics” studies

Who hasn’t heard of telomeres when we’re interested in aging? Epigenetic regulation phenomena? Sirtuins? If at least one of these themes speaks to you, it is because you have already set foot in the “omics” approaches, perhaps without knowing it!

Genomics, unlike genetics which studies genes one by one in a given individual or small population and their role in offspring, focuses on the analysis of the structure, function and editing of the genome as a whole. With this technique, it is possible to account for the overall function of a cell and its potential dysfunctions. Genomics also includes DNA sequencing, a technique increasingly used in disease diagnostics that, combined with bioinformatics, allows projections of the evolution of a cell or tissue. Thus, thanks to this tool, it is possible to determine the age of a cell but also its life expectancy, by measuring its telomeres for instance. This “omics” approach has also given rise to systems biology, thanks to which it is now possible to understand and model the function of complex organs.

Transcriptomics is a slightly more complicated approach, because it is an analysis that looks at all RNAs, coding or not. By coding we mean that an RNA will ultimately give a protein. The relatively recent discovery of non-coding RNAs has revolutionized this type of analysis, including previously unknown or misunderstood regulatory processes. As in genomics, it is possible to sequence the entire transcriptome, i.e. all the RNAs of a cell, including messenger RNAs (mRNAs that will give proteins), ribosomal RNAs (specific to ribosomes), Interfering RNAs (which interact with mRNAs leading to their degradation) and other non-coding RNAs (such as microRNAs, piwi-RNAs or nuclear RNAs, whose roles are still under study). All these data allow us to measure the expression of a gene in different tissues or conditions, thus giving us an overview of gene regulation, functions of a specific gene or changes in expression under pathological conditions.

omics
omics

Proteomics is more targeted and even less used than the two previous “omics” approaches. It is part of the study of the proteome, all the proteins of a cell. In these analyses, we can look at the changes that a protein undergoes during its synthesis: its translation, post-translational changes (such as acetylation, methylation…), its folding (the 3D structure of a protein being central to its function), its coupling with other proteins (formation of dimers, trimers or polymers ensuring adequate action of the protein in question) or its degradation. This discipline is mainly used to identify potential therapeutic targets or biomarkers of pathologies, but its applications are becoming more and more diversified, particularly on protein-DNA, protein-RNA and protein-protein interactions, thus joining genomics, transcriptomics and systems biology.

Metabolomics is based on the concept that each process taking place in a cell (the set of processes being called metabolism) leaves a chemical trace, before, during or after said process, in the form of a metabolite. By mapping the metabolites available in a cell, it is possible to account for its function and metabolism. This discipline is booming and requires important research, since the Human Metabolome Database lists about 3000 human metabolites at present, against nearly 50 000 in plants!

Long Long Life genomics proteomics, all things -omics, cell, longevity, transhumanism

Combining all these “omics” approaches, it is now possible to have an assessment of one’s biological age and to study the processes leading to physiological aging and its associated diseases. In this series of articles, we will see in more detail how the different “omics” work, what analytical techniques they use and their various applications in the fight against aging.

See all our articles on the “-omics” approaches

The “-omics” : a tool to better understand our aging process

omics

What is behind the term “-omics? When we talk of genomics, transcriptomics or proteomics, what are we looking at? Here is a guide to explain it all!

Part 1: Understanding genomics for anti-aging research

How can we not mention genomics and how useful they are. It is the oldest “-omics” approach and still the most studied one even today. It gave birth to whole new concepts, such as epigenetics or systems biology, and opened up the scientific community to new horizons that we had never even dreamed ot!

Part 2: Transcriptomics, a constantly evolving science.

The discovery of non coding RNA led to a Nobel Prize. Enough to say it’s an important field of research! Transcriptomics is allowing the discovery of new tools, new mechanisms and led us to better understand the regulation of transcription.

Part 3: Proteomics, a mish-mash of research fields

Above all, proteomics are a multidisciplinary approach, taking into account the interactions between fields, namely genomics and transcriptomics. It also refers to different concepts, from immunology to nutrition or cell function.

Part 4: Metabolomics, the last-born of the “omics”

Last but not least! Metabolomics is a field that helps us understand very complicated regulation networks and the daily discovery of new cell-cell communication players.

Part 5: The future of new “omics” approaches for anti-aging research

Nutriomics, lipidomics, glycomics… “omics” approaches are a constantly growing field. Here we will talk about all these topics for the future!

Dr. Marion Tible

Marion Tible Long Long Life

Author/Reviewer

Auteure/Relectrice

Marion Tible has a PhD in cellular biology and physiopathology. Formerly a researcher in thematics varying from cardiology to neurodegenerative diseases, she is now part of Long Long Life team and is involved in scientific writing and anti-aging research.

More about the Long Long Life team

Marion Tible est docteur en biologie cellulaire et physiopathologie. Ancienne chercheuse dans des thématiques oscillant de la cardiologie aux maladies neurodégénératives, elle est aujourd’hui impliquée au sein de Long Long Life pour la rédaction scientifique et la recherche contre le vieillissement.

En savoir plus sur l’équipe de Long Long Life

Back pain and FOXO, an anti-aging equation

Long Long Life FOXO anti-âge longévité transhimanisme

Back pain and FOXO, an anti-aging equation!

We keep on saying that aging is a major risk factor for the development of many neurodegenerative diseases, cardiovascular pathologies or cancers. But aging is also very often associated with the emergence of musculoskeletal pain. Among them, low back pain  is the most common disorder and it is believed that up to 75% of the population will be affected [1]. Moreover, up to 23% of these pains are chronic, meaning that they have been present for more than 3 months and are thus very disabling (severe loss of mobility)[1]. This chronic pain is caused by the degeneration of the intervertebral disc (IVD), a cartilage disc located between the vertebrae and used to cushion the shocks of the spine. Its degeneration is caused by changes in cells and their phenotype, as well as by impairments of the biochemical functions of the various IVD structures (annulus fibrosus and nucleus pulposus) [2]. However, very little is known about the molecular mechanisms upstream of these changes.

In a new research study [3], scientists focused on the FOXO (Forkhead box O) proteins in the degeneration of intervertebral discs. These proteins are transcription factors, playing a role in cell homeostasis and the maintenance of cell populations, and more generally in development, aging and longevity [2,4,5]. It has also recently been reported that the expression of some of these proteins was reduced in degenerated intervertebral discs in humans and during the aging of the spine of mice [6]. These characteristics prompted researchers to study the role of FOXO proteins in disc degeneration [3].

Long Long Life FOXO anti-aging longevity transhumanism - spine - low back pain

FOXO proteins control intervertebral disc homeostasis

Long Long Life FOXO anti-aging longevity transhumanism - low back pain

Experiments were conducted on mouse models lacking FOXO proteins. A deletion of all FOXO isoforms within the IVDs led to degeneration of the intervertebral discs. This degradation is driven by the loss of many cells in the central nucleus (nucleus pulposus) of the disc. Similarly, by inducing unique deletions of each FOXO isoform, it appeared that FOXO1 and FOXO3 were dominant in the structure of the disc and played an important part in homeostasis. FOXO deficiency in discs has also been associated with defective autophagy and decreased antioxidant defenses. Finally, it has been shown that these growth factors induce resistance to oxidative and inflammatory stress in nucleus pulposus cells [3]. FOXO transcription factors are therefore important regulators of IVD homeostasis.

In this study, researchers investigated the role of FOXO proteins in the aging process of intervertebral discs. Experiments have shown that these transcriptional factors play a major role in maintaining the homeostasis of intervertebral discs, and their deficiency within the disc structures leads to degeneration.  This is, to the scientists’ knowledge, the first study to provide evidence that these growth factors regulate homeostasis and aging of intervertebral discs[2]. Through their research, the scientists have shown that targeting FOXO proteins can become a therapeutic strategy to delay the age-related degeneration of the intervertebral discs that cause chronic low back pain.

Anne Fischer

Long Long Life Anne Fischer icon

Author

Auteur

Anne is studying medicine science at the Institute of Pharmaceutical and Biological Science in Lyon and she has graduated with a Bachelor’s degree in molecular and cellular biology at the University of Strasbourg.

More about the Long Long Life team

Anne étudie les sciences du médicament à l’Institut des Sciences Pharmaceutiques et Biologiques de Lyon. Elle est titulaire d’une licence en biologie moléculaire et cellulaire de l’Université de Strasbourg.

En savoir plus sur l’équipe de Long Long Life

References :

[1] https://www.lombalgie.fr

[2] Tiffany Kadow MD, Gwendolyn Sowa MD, PhD, Nam Vo PhD, James D. Kang MD, Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions? Clin Orthop Relat Res (2015) 473:1903–1912 DOI 10.1007/s11999-014-3774-8

[3] Alvarez‐Garcia O, Matsuzaki T, Olmer M, et al. FOXO are required for intervertebral disk homeostasis during aging and their deficiency promotes disk degeneration. Aging Cell. 2018;e12800. https://doi.org/10.1111/acel.12800

[4] Rute Martins, Gordon J. Lithgow and Wolfgang Link, Long live FOXO: unraveling the role of FOXO proteins in aging and longevity, Aging Cell (2016) 15, pp196–207

[5] Ashley E. Webb and Anne Brunet, FOXO transcription factors: key regulators of cellular quality control, Trends Biochem Sci. 2014 April ; 39(4): 159–169 doi:10.1016/j.tibs.2014.02.003

[6] Alvarez‐Garcia, O., Matsuzaki, T., Olmer, M., Masuda, K., & Lotz, M. K. (2017). Age‐related reduction in the expression of FOXO transcription factors and correlations with intervertebral disc degeneration. Journal of Orthopaedic Research, 35, 2682–2691

Has human longevity reached its limits?

Long Long Life longévité humaine thérapie anti-vieillissement transhumanisme

Has human longevity reached its limits?

Human existence, as it is known today, is limited in its duration and the risk of death increases with age. At least that’s what most people naturally think. But this was without relying on the latest study on this topic, published last week in Science [1]. This study, conducted on an Italian population, analysed the mortality rate of individuals aged 105 and over between 2009 and 2015 (a total of 3836 people). The results of this statistical analysis seem to show that the risk of dying stabilizes after age 105.

The age-related mortality rate can be plotted on a graph: the curve increases exponentially with age. It is scientifically accepted that this rate increases exponentially until around the age of 80-90. Then, the opinions are very divergent: we have on one side, those who believe in the existence of a “mortality plateau” after this age, which reflects the stabilization of the mortality rate, and on the other side, those who refute this hypothesis and think that the exponential increase in the mortality rate persists beyond 80 years.

The limits of human longevity: a divisive subject

In a publication released in 2016 [2], geneticists had proposed that there was a limit to human life span. Analyzing global demographic data, they concluded that there had been no improvement in human longevity since the end of the 20th century, the record being 122 years, held by the French Jeanne Calment. However, in its recent analysis, Professor Elisabetta Barbi’s team has, on the contrary, shown that there is a plateau of mortality risk after the age of 105, suggesting that there is no limit to human longevity. With such a mortality plateau, the risk of death from one birthday to another after age 105 is roughly one in two [3]. Such a phenomenon suggests that a person who has reached the age of 105 could still live for a very long time [3].

Long Long Life human longevity transhumanism anti-aging therapies

This study was conducted after checking the age of the people included in the survey on their birth certificate. The purpose of this process was to avoid errors in the data linked to age overstatement often found in very old people [1]. The risk of dying according to age has been an intriguing fact for a long time. Since Gompertz’s law in the 19th century which states that the mortality rate increases exponentially with age, the question arises as to the existence of a mortality plateau after a certain age. It was not until the end of the 20th century and the increase in the amount of available and reliable data to accelerate research on this subject [1], but the controversy is still present.

This last study put forward the existence of a mortality plateau within an Italian population of supercentenarians (105 years and older), just like other studies that have shown the same result, particularly in small organisms [4]. It revives the debate on the limit of human longevity, which for them does not seem to have been reached [1]. Such a result could encourage demographic studies on the mortality rate related to age and human lifespan, to understand the mechanisms of human longevity.

Anne Fischer

Long Long Life Anne Fischer icon

Author

Auteur

Anne is studying medicine science at the Institute of Pharmaceutical and Biological Science in Lyon and she has graduated with a Bachelor’s degree in molecular and cellular biology at the University of Strasbourg.

More about the Long Long Life team

Anne étudie les sciences du médicament à l’Institut des Sciences Pharmaceutiques et Biologiques de Lyon. Elle est titulaire d’une licence en biologie moléculaire et cellulaire de l’Université de Strasbourg.

En savoir plus sur l’équipe de Long Long Life

References:

[1] Barbi et al., Science 360, 1459–1461 (2018) DOI: 10.1126/science.aat3119

[2] Xiao Dong, Brandon Milholland & Jan Vijg, Evidence for a limit to human lifespan, 13 October 2016, VOL 538, NATURE, 257-259 doi:10.1038/nature19793

[3] Elie Dolgin, There’s no limit to longevity, says study that revives human lifespan debate, Nature 559, 14-15 (2018) doi: 10.1038/d41586-018-05582-3

[4] Natalia S. Gavrilova and Leonid A. Gavrilov, Biodemography of Old-Age Mortality in Humans  and Rodents, J Gerontol A Biol Sci Med Sci. 2015 January;70(1):1–9 doi:10.1093/gerona/glu009

Understanding genomics for anti-aging research

génomique

Genomics is the study of the genome, that is to say, the entirety of our DNA. Knowing that if we unfolded all the DNA contained in our body, that could cover 1000 times the distance from the Earth to the Sun, we can wonder how it is possible to analyze such an amount of data!

Genomics: how to analyze a genome

understanding- genomics -anti-aging-research-long-long-life-longevity-transhumanism

In 1953, Watson & Crick, two researchers basing their work on Wilkins & Franklin crystallographic data have succeeded in solving mystery of DNA structure, opening up a whole new field of study, especially concerning DNA replication and transcription processes. Sequencing was still far away but the idea took form among the researchers and in 1965, the first transcriptome was sequenced. It was that of a yeast, Saccharomyces cerevisiae[1]. However, though RNA is good, DNA is better! Technological advances have made it possible to develop different sequencing techniques, which won Gilbert & Sanger a Nobel Prize in chemistry in 1970. Finally, in 1977, the first genome to be fully sequenced belonged to a bacteriophage virus[2].

Hpw does one sequence a genome?

Sequencing by the Sanger method[3] – by enzymatic synthesis

It is the most widely used technique today and many improvements have been made since the 1970s. The principle is relatively simple and based on the same mechanism as natural DNA replication: a primer (a small DNA sequence) will initiate the synthesis of a DNA strand complementary to the one we want to sequence, a DNA polymerase will elongate this strand, then a mixture of deoxyribonucleotides (dATP, dCTP, dGTP and dTTP) and di-deoxyribonucleotides (ddATP, ddCTP, ddGTP or ddTTP) will be introduced into the mixture. Deoxyribonucleotides will be normally integrated and participate in DNA strand synthesis (and give adenine, cytosine, guanine and thymine, the four bases of DNA). On the other hand, the di-desoxyribonucleotides (homologues of deoxyribonucleotides but not having the chemical group necessary for the action of the DNA polymerase), will integrate into the strand during synthesis and cause it to break. Thus, if ddCTP has been introduced into the mixture, the strand being synthesized will cut at each cytosine. For complete sequencing, simply repeat with the remaining three di-deoxyribonucleotides. The experimenter will end up with DNA fragments of different lengths for which they will know exactly on which di-deoxyribonucleotide they were broken. Each fragment is analyzed and reordered according to its molecular weight, allowing the exact DNA sequence to be found.

Gilbert sequencing[4] – chemical degradation

Unlike Sanger’s method, the Gilbert method is based on DNA degradation: the goal is to achieve selective cuts through chemical processes breaking DNA into fragments, which will be put back in order later. Once the DNA of interest is marked with a radioactive tracer, it is denatured (double stranded to single stranded) and subjected to chemical modifications, developed by Gilbert himself, specific to each base constituting the DNA. At the modification site, the DNA is then cut and each fragment is analyzed and returned in the order of its molecular weight (as for the Sanger method).

understanding-genomics-anti-aging-research-long-long-life-longevity-transhumanism

How to sequence an entire genome

Both of the above techniques have been greatly improved since their discovery, particularly in terms of sample preparation, separation and DNA fragment detection. These advances have made it possible to automate sequencing with increasingly efficient machines. However, the entire genome represents several billion bases and no machine today has the capacity to process so much information. It is necessary to prepare the DNA, by treating it with restriction enzymes or ultrasound, in order to obtain fragments that can be sequenced. The advent of bioinformatics and nanotechnologies has also revolutionized the field to create genomics as we know it today.

HTS, NGS, microarray, GWAS… What’s all this?

The latest developments in sequencing have given rise to many acronyms, not always easy to understand. HTS stands for High-Throughput Sequencing. It is often associated with NGS, “Next Generation Sequencing“, because the two approaches emerged in the early 2000s and overlap[5]. The aim of these techniques is to increase the number of decoded sequences per series of analyses, up to a few million DNA fragments, while lowering the cost of these tests. They have revolutionized genomics by making previously complex and expensive studies accessible in terms of time and money. They also make it possible, and this is a revolution in itself, to analyse a single copy of DNA, thus making it possible to analyse very small samples[5].

Pyrosequencing, which is part of HTS/NGS, is currently the most widely used: it is based on the Sanger method but uses pyrophosphate nucleotides instead of di-desoxyribonucleotides. When they are incorporated into the DNA strand during synthesis, instead of stopping the elongation, they will release a pyrophosphate that will be transformed and emits light. The result is a graph with peaks that show the incorporation of the marked nucleotides, and whose height reflects the number of nucleotides integrated into the DNA sequence. With bioinformatic tools, it is then possible to determine the DNA sequence. The major interest of this technique is the parallel analysis of several thousand fragments, allowing results to be obtained in a few hours[5].

understanding-genomics-anti-aging-research-long-long-life-longevity-transhumanism

DNA chips, or “DNA-microarray“, use a completely different mechanism: known DNA sequences are attached to a plate (the chip) and the DNA to be tested is injected onto that surface. When it is complementary to a sequence on the chip, it hybridizes, emits detectable light and we obtain a hybridization spectrum that can give us several information: expression level of a given gene, mutations, sequencing, interactions with other molecules… [6]

The GWAS approach, “Genome-Wide Association Studies“, is a genetics technique crossed with genomics. As the name suggests, it studies genetic mutations, not at the level of a gene but by taking into account the entire genome. It is not a sequencing technique strictly speaking, but it allows mutations to be identified quickly and reliably[7]. It highlights mostly what are called SNPs, “single nucleotide polymorphism”, which correspond to mutations of a single base within a complete DNA sequence. It then links these SNPs to known diseases, thus linking the occurrence of a mutation to a pathological situation[7].

More recently, single-cell genomics have emerged, with the ambition of obtaining information on the DNA of a single cell[8]. Unlike other techniques that draw their data from thousands of cells, this approach wishes to take into account the heterogeneity of cell populations and the genomic diversity existing between cells in the same organ.

Genomics applied to aging and age-related diseases

We talked about the different techniques of genome analysis, so now what can we do with the data obtained? Sequencing provides thousands of pieces of information that must then be processed. The obvious application is the correlation between genome changes and existing diseases, an approach similar to GWAS. Thanks to sequencing, we can also identify mutations appearing de novo, rare mutations that other techniques cannot discern, or highlight gene variants, giving us new therapeutic perspectives[6].

Genetics, Genomics and Epigenomics

Genetics differs from genomics in its more targeted approach, focusing on a specific gene, its possible mutations and its transmission. Genomics, as we have seen, is concerned with the entire genome and its variations. This type of study has given rise to new areas of research, the most important of which is epigenomics: a mixture of genomics and epigenetics. Like genomics and genetics, epigenomics differs from epigenetics in its subject of study, the genome, or more specifically the epigenome, which represents all changes in the genetic material of a cell (). By combining these approaches, genomic maps are obtained, showing mutations, polymorphisms, genetic variants or DNA methylation rates[9].

understanding-genomics-anti-aging-research-long-long-life-longevity-transhumanism

Cancer

Several teams around the world have looked at comparing the genome of normal cells to that of cancer cells, particularly in terms of structural variants. A structural variant is a small segment of DNA whose sequence remains the same but which changes conformation (inversion, translocation) giving rise to cellular diversity, beneficial only up to a certain stage[10]. These variants are involved in many diseases, when their rate increases, but remain very difficult to detect. Genomic techniques are the only ones that can identify them, thanks to the use of mathematical algorithms that allow such fine analysis of data that they can find rare nucleotide variants (a few bases and no longer an entire segment)[11, 12]. The development of WGS (whole-genome sequencing) analysis techniques has also made it possible to identify mutations appearing de novo, i.e. not inherited from the parents. Conrad et al. estimated these mutations at about 74 per germ line (the one that gives eggs and sperm)[13]. These mutations are particularly harmful and interesting for sporadic diseases because they are not subject to the natural selection that takes place when a gene passes from one individual to another.

These approaches are very complementary and now make it possible to validate what pathologists saw under the microscope, namely that not all cancer cells are necessarily alike. Several teams have demonstrated this heterogeneity, both phenotypic and genetic[14], by adding a notion of evolution. Indeed, primary tumours and metastases do not seem to have exactly the same genome and adapt to external pressures, such as chemotherapy. This information made it possible to correctly characterize the different types of tumours and predict the progression or relapse of a cancer. Beyond this diagnostic and preventive assistance, genomics also makes it possible to consider ultra-targeted and personalized therapies[15].

Neurodegenerative diseases

understanding-genomics-anti-aging-research-long-long-life-longevity-transhumanism

Using blood samples, several teams have been working to decipher the genome of neurodegenerative diseases, and more particularly Alzheimer’s disease, the most studied and prevalent of them. Thanks to their work, genes have been identified, notably APOE, CD33 or EPHA1, and their polymorphisms seem to be associated with the development of Alzheimer’s disease. For example, CR1 (chromosome 1) and CLU (chromosome 8) have two loci (a polymorphic zone specific to the gene) very strongly associated with the occurrence of Alzheimer’s disease[17]. In addition to these discoveries, genomics has also made it possible to find previously unknown mutations on “classical” Alzheimer’s disease genes, in particular APP (coding for the amyloid precursor) and MAPT (coding for the Tau protein).

Finally, the most important contribution of genomics to this type of disease is the study of the epigenome, a daughter discipline of genomics. Increasingly, the study of methylation, folding and DNA modification, as well as the study of gene expression regulation phenomena, are crucial tools for understanding the development of neurodegenerative pathologies[18]. For more information, you can visit the NIAGADS website, which lists all public genomic studies in progress. The same type of studies can be found for cardiovascular diseases and metabolic pathologies such as diabetes. All GWAS studies are listed on the site of the National Genome Research Institute and highlight 11 genes for Alzheimer’s disease, 42 genes for cardiovascular disease and 25 genes for diabetes, whose polymorphisms and/or mutations are linked to the occurrence and/or severity of these pathologies.

Towards anti-aging genomics?

Genomics can also be used to determine the propensity of a cell to become senescent and several studies have already shown a difference between senescent phenotypes and others[19]. Aging regulation genes have also been identified, with polymorphisms predisposing to a more or less long lifespan. This is the case of CEBPB, a gene involved in muscle metabolism and whose polymorphisms are risk factors for the occurrence of age-related sarcopenias, which greatly shorten life expectancy[20].

Thanks to all this genomics research, hundreds of researchers have been able to identify common denominators predisposing to age-related diseases. Beyond a diagnostic approach, many of us hope to one day see the emergence of a therapeutic and preventive arsenal in order to manage aging as a whole.

See all our articles on the “-omics” approaches

The “-omics” : a tool to better understand our aging process

omics

What is behind the term “-omics? When we talk of genomics, transcriptomics or proteomics, what are we looking at? Here is a guide to explain it all!

Part 1: Understanding genomics for anti-aging research

How can we not mention genomics and how useful they are. It is the oldest “-omics” approach and still the most studied one even today. It gave birth to whole new concepts, such as epigenetics or systems biology, and opened up the scientific community to new horizons that we had never even dreamed ot!

Part 2: Transcriptomics, a constantly evolving science.

The discovery of non coding RNA led to a Nobel Prize. Enough to say it’s an important field of research! Transcriptomics is allowing the discovery of new tools, new mechanisms and led us to better understand the regulation of transcription.

Part 3: Proteomics, a mish-mash of research fields

Above all, proteomics are a multidisciplinary approach, taking into account the interactions between fields, namely genomics and transcriptomics. It also refers to different concepts, from immunology to nutrition or cell function.

Part 4: Metabolomics, the last-born of the “omics”

Last but not least! Metabolomics is a field that helps us understand very complicated regulation networks and the daily discovery of new cell-cell communication players.

Part 5: The future of new “omics” approaches for anti-aging research

Nutriomics, lipidomics, glycomics… “omics” approaches are a constantly growing field. Here we will talk about all these topics for the future!

References

[1] R.W. Holley, et al., Structure of a ribonucleic acid, Science, 1965;147:1462–1465

[2] Sanger, et al., Nucleotide sequence of bacteriophage phi X174 DNA, Nature 1977;265:687–695

[3] F. Sanger, A. Coulson, A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase, J. Mol. Biol. 1975;94:441–448

[4] M. Maxam, W. Gilbert, A new method for sequencing DNA, Proc. Natl. Acad. Sci. U. S. A. 1977;74:560–564

[5] JA. Reuter, DV. Spacek, MP. Snyder, High-Throughput Sequencing Technologies, Molecular Cell, 2015;58(4):Pages 586-597

[6] DC. Koboldt, KM. Steinberg, DE. Larson, RK. Wilson, ER. Mardis, The Next-Generation Sequencing Revolution and Its Impact on Genomics, Cell, 2013;155(1):27-38

[7] Marchini J, Howie B. “Genotype imputation for genome-wide association studies”. Nature Reviews. Genetics. 2010;11(7):499–511

[8] Macaulay IC, Voet T. Single Cell Genomics: Advances and Future Perspectives. Maizels N, ed. PLoS Genetics. 2014;10(1):e1004126

[9] Ben-Avraham D, Muzumdar RH, Atzmon G. Epigenetic genome-wide association methylation in aging and longevity. Epigenomics. 2012;4(5):503-509

[10] Tattini L, D’Aurizio R, Magi A. Detection of Genomic Structural Variants from Next-Generation Sequencing Data. Frontiers in Bioengineering and Biotechnology. 2015;3:92

[11] C.T. Saunders, W.S. Wong, S. Swamy, J. Becq, L.J. Murray, R.K. Cheetham Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs, Bioinformatics, 2012;28:1811-1817

[12] K. Cibulskis, M.S. Lawrence, S.L. Carter, A. Sivachenko, D. Jaffe, C. Sougnez, S. Gabriel, M. Meyerson, E.S. Lander, G. Getz Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples, Nat. Biotechnol., 2013;31:213-219

[13] D.F. Conrad, J.E. Keebler, M.A. DePrist et al., 1000 Genomes Project, Variation in genome-wide mutation rates within and between human families, Nat. Genet., 2011;43:712-714

[14] P.J. Campbell, S. Yachida, L.J. Mudie et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer, Nature, 2010;467:1109-1113

[15] Uzilov AV, Ding W, Fink MY, et al. Development and clinical application of an integrative genomic approach to personalized cancer therapy. Genome Medicine. 2016;8:627

[16] Antunez C., Boada M., Gonzalez-Perez A., Gayan J., Ramirez-Lorca R., Marin J. The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer’s disease. Genome Med. 2011;3:33

[17] Lambert J.C., Heath S., Even G., Campion D., Sleegers K., Hiltunen M. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet. 2009;41:1094–1099

[18] Condliffe D., Wong A., Troakes C., Proitsi P., Patel Y., Chouliaras L. Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer’s disease brain. Neurobiol Aging. 2014;35:1850–1854

[19] Pilling LC, Harries LW, Powell J, Llewellyn DJ, Ferrucci L, Melzer D. Genomics and Successful Aging: Grounds for Renewed Optimism? The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2012;67A(5):511-519

[20] Hicks GE, Shardell M, Alley DE, Miller RR, Bandinelli S, Guralnik J, Lauretani F, Simonsick EM, Ferrucci L, Absolute strength and loss of strength as predictors of mobility decline in older adults: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2012;67(1):66-73

Dr. Marion Tible

Marion Tible Long Long Life

Author/Reviewer

Auteure/Relectrice

Marion Tible has a PhD in cellular biology and physiopathology. Formerly a researcher in thematics varying from cardiology to neurodegenerative diseases, she is now part of Long Long Life team and is involved in scientific writing and anti-aging research.

More about the Long Long Life team

Marion Tible est docteur en biologie cellulaire et physiopathologie. Ancienne chercheuse dans des thématiques oscillant de la cardiologie aux maladies neurodégénératives, elle est aujourd’hui impliquée au sein de Long Long Life pour la rédaction scientifique et la recherche contre le vieillissement.

En savoir plus sur l’équipe de Long Long Life

Quercetin supplements: anti-aging, anti-inflammatory!

Quercétine pill bottle - long long life anti aging transhumanism longevity supplement

Quercétine pill bottle - long long life anti aging transhumanism longevity supplement

Fact sheet

Quercetin: anti-aging flavonoid

Quercetin is a pigment found naturally in many foods, such as onions, capers, olive oil and some legumes. Like many flavonoids, it is an antioxidant and a fairly powerful anti-inflammatory. Initially used in the treatment of asthma and allergic reactions[1], its role has proved interesting in the fight against inflammation[2] and the prevention of cardiovascular diseases[3]. Today, quercetin is the subject of new studies, as it seems to be important in the fight against aging and its associated diseases.

Intérêt
Preuve d'efficacité
Accessibilité

Long Long Life does not sell any of these products. We believe this to be the price of freedom.

Since we have no financial interest in this, we can tell you the whole truth on the treatments being developped to fight against aging, and give you the best information possible.

Quercetin and age-related pathologies

First demonstrated in cell cultures (in vitro) then on animals (in vivo), the efficacy of quercetin on humans remains a subject of discussion within the scientific community.

Quercetin supplementation seems to have beneficial effects on neurodegenerative diseases: in mice, it reduces amyloid β and tauopathies in the brain of a transgenic mouse model mimicking Alzheimer’s disease. In addition to these neuropathological impacts, quercetin increases learning performance and spatial memory, two degraded functions in Alzheimer’s disease[4]. Combined with physical exercise, known for its neuroprotective benefits, quercetin also has a defensive role against neuron loss[5]. This action seems possible thanks to the upward regulation of a signalling pathway involved in the antioxidant and anti-apototic activity of neuronal cells, the PI3K/Akt pathway. It is complemented by an effect on the eIF2α pathway, a major inflammatory pathway, the regulation of which plays a primary role in neuroprotection[6].

In addition to its action on neurodegenerative diseases, quercetin seems to have a protective effect against cancers, in particular prostate cancer[7]. Thanks to its antioxidant activity, quercetin is indeed able to intervene on the signaling pathways regulating apoptosis and cell migration, two cornerstones of the development of cancer[8]. It also has a preventive role with regard to cardiovascular diseases[9].

Can quercetin slow down aging?

New studies suggest that quercetin could reduce cell senescence, a phenomenon affecting part of our cells, preventing them from dying but at the same time restricting their normal functions. In cultures of human senescent cells, a team recently proved an inhibition of the phenomena leading the cells to a senescence phenotype thanks to quercetin[10]. More impressive, on fibroblastic cells (cells supporting the skin), a second study showed a reversal of senescence, an interesting finding in the treatment of skin aging (short term) but also in the treatment of systemic cell senescence (in the longer term)[11]. In parallel, quercetin seems to have an effect on AGEs (Advanced Glycation End-products) which, during aging, lead to the formation of free radicals and the occurrence of metabolic diseases, such as diabetes[12].

Quercetin is therefore a molecule of interest, despite the absence of clinical studies, whose capabilities need to be investigated to fully determine its anti-aging potential.

  • Number publications : about 500
  • Availability : over the counter
  • Route : oral
  • Dosage : 200-500 mg / dose, in 2 to 3 takes in a day

No side effects have been described to date. However, quercetin can interact with cyclosporin (an anti-rejection drug intended mainly for transplant patients) and inhibits the action of quinolone antibiotics.

Important note: a recent study demonstrated possible thyroid toxicity, inhibiting cell growth induced by thyroid hormones and decreasing its iodine binding capacity[13]. It is therefore important to remain cautious about quercetin, and more broadly flavoinoids, and not to take them if you have any doubt about the health of your thyroid.

Finally, the bioavailability of quercetin remains a major topic in human studies. Indeed, out of an ingested dose, only 20% will actually be absorbed[14].

[1] Thornhill SM, Kelly AM. Natural treatment of perennial allergic rhinitis. Altern Med Rev. Review. 2000;5(5):448-54

[2] Katske F, Shoskes DA, et al. Treatment of interstitial cystitis with a quercetin supplement. Tech Urol. 2001;7(1):44-6

[3] Edwards RL, Lyon T, et al. Quercetin reduces blood pressure in hypertensive subjects.  J Nutr. 2007;137(11):2405-11

[4] Maria S-GA, Ignacio M-MJ, Ramírez-Pineda Jose R, Marisol L-R, Edison O, Patricia C-GG. The flavonoid quercetin ameliorates Alzheimer’s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice. Neuropharmacology. 2015;93:134-145

[5] Chang HC, Yang YR, Wang PS, Wang RY, Quercetin enhances exercise-mediated neuroprotective effects in brain ischemic rats, Med. Sci. Sports & Ex. 2014;46(10):1908-16

[6] Hayakawa M, Itoh M et al., Quercetin reduces eIF2α phosphorylation by GADD34 induction, Neurobiol. Aging, 2015;36(9):2509-18

[7] Nöthlings U, Murphy SP, et al. Flavonols and pancreatic cancer risk: the multiethnic cohort study. Am J Epidemiol. 2007;166(8):924-31

[8] Nam JS, Sharma AR, Nguyen LT, Chakraborty C, Sharma G and Lee SS, Application of Bioactive Quercetin in Oncotherapy: From Nutrition to Nanomedicine (review), Molecules 2016;21(1):108

[9] Khurana S, Venkataraman K, Hollingsworth A, Piche M, Tai TC. Polyphenols: Benefits to the Cardiovascular System in Health and in Aging. Nutrients. 2013;5(10):3779-3827

[10] Yang HH, Hwangbo K, Zheng MS et al. Quercetin-3-O-β-d-glucuronide isolated from Polygonum aviculare inhibits cellular senescence in human primary cells, Arch. Pharm. Res. 2014;37(9):1219-33

[11] Chondrogianni N, Kapetan S, Chinou I, Vassilatou K, Papassideri K,Gonos ES, Anti-ageing and rejuvenating effects of quercetin, Experimental Gerontology, 2010;45(10):763-71

[12] Alam M, Ahmad I, Naseem I, Inhibitory effect of quercetin in the formation of advance glycation end products of human serum albumin: An in vitro and molecular interaction study, Int. J. Biol. Macromolecules, 2015;79:336-343

[13] Giuliani C, Bucci I, Di Santo S, et al, The flavonoid quercetin inhibits thyroid-restricted genes expression and thyroid function, Food and Chemical Toxicology, 2014;66:23-29

[14] X. Cai, Z. Fang, J. Dou, A. Yu and G. Zhai, Bioavailability of Quercetin: Problems and Promises, Current Medicinal Chemistry, 2013;20:2572-2582

DISCLAIMER

The information on the present website does not constitute either directly or indirectly any medical advice. The provided information is intended to inform and is in no way a substitute for the direct relationship between a patient and a health professional. Under no circumstances the information on the website are likely to make up for consulting, visiting and diagnosis by a licensed healthcare professional. Said information should not be interpreted as ensuring the promotion any some molecules or medical products.

Long Long Life will not be held liable for any action or decision-making in relation to the information on this website.

Long Long Life does not guarantee by any means any result following the implementation of the published information on the website herein.

Self-medication can be dangerous for your health, please seek medical advice before starting any treatment.

Dr. Marion Tible

Marion Tible Long Long Life

Author/Reviewer

Auteure/Relectrice

Marion Tible has a PhD in cellular biology and physiopathology. Formerly a researcher in thematics varying from cardiology to neurodegenerative diseases, she is now part of Long Long Life team and is involved in scientific writing and anti-aging research.

More about the Long Long Life team

Marion Tible est docteur en biologie cellulaire et physiopathologie. Ancienne chercheuse dans des thématiques oscillant de la cardiologie aux maladies neurodégénératives, elle est aujourd’hui impliquée au sein de Long Long Life pour la rédaction scientifique et la recherche contre le vieillissement.

En savoir plus sur l’équipe de Long Long Life

Growth hormone as an anti-aging treatment for women?

Growth hormone as an anti-aging treatment for women?

Growth hormone (hGH) is a molecule synthesized by the body, essential for human growth and development. hGH specifically boosts the secretion by the liver of IGF (Insulin-like Growth Factor), necessary for cartilage growth and cell proliferation[1]. Alterations in growth hormone or its signalling pathway lead to multiple pathologies[2]. Nevertheless, decreased dialogue between hGH and the IGF-1 receptor (also known as IGF-1R for Insulin-like Growth Hormone 1 Receptor) in later life, particularly in females, appears to be associated with increased longevity. Indeed, it has been shown that the decrease in the cellular signal passing through these two proteins improves the longevity of many organisms[3] and that a mutation of the receptor at the IGF in female mice lengthens their lifespan[4].

Long-Long-Life-growth hormone-omatotropine-antiaging-longevity-women-150x150

These observations on animal models have raised questions among scientists about the effect of hGH/IGF-1R signalling on human longevity. The discovery of mutations in the IGF-1R gene in individuals with exceptional longevity[5], and the extension of the healthy life span of nonagenarians carrying mutations in the IGF-1R gene[3], correlate with the results of experiments on animal models. In these two studies, the reduction in signalling on this route affects and benefits only women. In view of the positive effects of this phenomenon on longevity, new therapeutic strategies are currently being studied. This is the case of monoclonal antibodies directed against IGF-1R that prevent the binding of growth hormone to its receptor, thereby disrupting the signal.

Targeting growth hormone (hGH) : pioneer study

Long-Long-Life-growth hormone-omatotropine-antiaging-longevity-women-150x150

It is this therapeutic model that an American team of researchers recently studied. For their study[6] published in Nature Communication, scientists chronically administered a monoclonal antibody directed against IGF-1R in female and male mice, delaying the aging of female mice. The antibody used was specially designed for the murine model and is selective for IGF-1R. The analyses showed good results and a good tolerance to the treatment, even when the treatment was administered after the age of 18 months (elderly mice)[6]. In correlation with previous studies, the treatment showed better benefits in females since it increased their life span by 9%. Preventing signaling of this pathway has also improved cardiac function, and decreased tumours and inflammation in female mice[6]. Again, decreased hGH pathway signalling was associated with longevity in female mammals, but the main finding of the study was that monoclonal antibodies to IGF-1R delayed aging with chronic treatment and in elderly mice[6].There is growing evidence of the value of targeting the hGH pathway at an advanced age for its positive impact on longevity. The results observed in mice suggest, first, that the effects can be reached at an advanced age and, second, that monoclonal antibodies directed against IGF-1R could become a therapeutic means of delaying aging. These results also stand out because they show a unique case where modulation of cell function for healthy lifetime and longevity benefits only females. This observation reminds us of the importance of considering gender differences in anti-aging research to develop more effective treatments.

Anne Fischer

Long Long Life Anne Fischer icon

Author

Auteur

Anne is studying medicine science at the Institute of Pharmaceutical and Biological Science in Lyon and she has graduated with a Bachelor’s degree in molecular and cellular biology at the University of Strasbourg.

More about the Long Long Life team

Anne étudie les sciences du médicament à l’Institut des Sciences Pharmaceutiques et Biologiques de Lyon. Elle est titulaire d’une licence en biologie moléculaire et cellulaire de l’Université de Strasbourg.

En savoir plus sur l’équipe de Long Long Life

References :

[1] Andrew J. Brooks and Michael J. Waters. The growth hormone receptor: mechanism of activation and clinical implications, nature reviews, endocrinology volume 6, september 2010, 515-525.

[2] https://en.wikipedia.org/wiki/Growth_hormone

[3] Sofiya Milman, Gil Atzmon, Derek M. Huffman, Junxiang Wan, Jill P. Crandall, Pinchas Cohen and Nir Barzilai. Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity, Aging Cell (2014) 13, pp769–771 Doi:10.1111/acel.12213

[4] Martin Holzenberger, Joëlle Dupont, Bertrand Ducos, Patricia Leneuve, Alain Géloën, Patrick C. Even, Pascale Cervera & Yves Le Bouc. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice, NATURE | VOL 421 | 9 JANUARY 2003

[5] Suh et al. Functionally significant insulin-like growth factor I receptor mutations in centenarians, PNAS  March 4, 2008 vol. 105 no. 9, 3438–3442.

[6] Kai Mao, Gabriela Farias Quipildor, Tahmineh Tabrizian, Ardijana Novaj, Fangxia Guan, Ryan O. Walters, Fabien Delahaye, Gene B. Hubbard, Yuji Ikeno, Keisuke Ejima, Peng Li, David B. Allison, Hossein Salimi-Moosavi, Pedro J. Beltran, Pinchas Cohen, Nir Barzilai & Derek M. Huffman. Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice, NATURE COMMUNICATIONS | (2018) 9:2394 | DOI: 10.1038/s41467-018-04805-5.

Glutathione benefits for life extension

A pill bottle titled Glutathione on a pink background - long long life supplement transhumanism longevity

Glutathione pill bottle -long long life transhumanism glutathione benefits longevity supplement

Fact sheet

Glutathione balances oxidation

Glutathione is a peptide composed of three condensed molecules, which plays a central role in maintaining the redox potential (oxidizer/reducer balance) within our cells. Due to its ability to exist in reduced or oxidized form, glutathione is a true “electron trap”, placing it very high on the list of antioxidants. Its metabolism is intimately linked to that of selenium because the enzyme that glutathione forms by coupling with selenium (glutathione peroxidase) allows the detoxification of free radicals (notably H2O2)[1].

Interest
Efficiency
Availability

Long Long Life does not sell any of these products. We believe this to be the price of freedom.

Since we have no financial interest in this, we can tell you the whole truth on the treatments being developped to fight against aging, and give you the best information possible.

Glutathione: great multitask longevity supplement

Glutathione is involved in a wide variety of phenomena and, indeed, plays a multi-factorial role in aging. Overall, there is a decrease of the glutathione levels during our lives and this seems to impact the onset of diseases[2]. This decrease is not as simple as it seems, because although we do see a fall in the reduced form of glutathione (GSH, antioxidant), a parallel increase in its oxidized form can be observed (GSSG).

Neurodegenerative diseases

This decline is particularly associated with the onset of Parkinson’s disease and other neurodegenerative diseases[3]. In Alzheimer’s disease, several studies have demonstrated the central role of glutathione, because of its antioxidant activity: an increase in the oxidized form of glutathione in the blood and brain was found in mouse models of Alzheimer’s disease, no matter the age of the mouse[4]. These studies therefore seem to indicate GSH deficiency/SSG surplus as a precursor of neurodegenerative diseases[5]. In addition to these studies, others have examined the therapeutic effect of glutathione, demonstrating the neuro and glio-protective capacity of glutathione supplementation[6, 7].

Cardiovascular diseases

The decrease in glutathione is also observed in the heart over time. It appears that the enzymes derived from glutathione also vary with age, in a tissue-dependent manner. For example, glutathione peroxidase remains stable in the heart but decreases in the liver, while glutathione reductase increases in both tissues over time[8]. The total result of these variations causes a decrease in the antioxidant capacity of our body during aging. A supplementation in glutathione could thus restore the balance between GSH and GSSG, allowing our body to find a more important antioxidant potential.

Glutathione and cell apoptosis?

In addition to the impact of its reduction on the incidence of age-related diseases, glutathione appears to play a role in apoptosis (the programmed death of our cells). By mechanisms that are still unclear, its metabolism is linked to the activation of caspase-3, a major pro-apoptotic protein, and BCl-2, the regulator of mitochondrial apoptosis[9, 10]. A recent study also looked at the links between glutathione and apoptosis in the hearts of diabetic mice, showing that its presence reduced necrosis and increased apoptosis, a protective mechanism of the heart in these conditions[11].

Glutathione as a life extension supplement

Glutathione is very promising for the extension of the lifespan. Preliminary studies in C. Elegans actually show an activation of the sirtuin pathway with GSH supplementation, increasing the lifespan of these small worms by about 30%[12].

The interest of glutathione is obvious in the fight against aging. However, one of the major problems remains its bioavailability. Oral supplementation is ineffective because glutathione is destroyed at the digestive level. It must therefore pass directly into the bloodstream. Gastro-resistant pills have recently appeared on the market but studies tend to agree that the bioavailability of glutathione taken in this form is far from optimal. A research team tried to introduce glutathione precursors into the diet of elderly people, with success: GSH levels were restored when taking cysteine and glycine together, suggesting a possible oral supplementation[13].

  • Number of publications: about 4000
  • Availability : over the counter
  • Route : intravenous/inhalation, possibly sublingual. If possible, it is recommended to combine its supplementation with selenium to maximize its action.
  • Dosage : 100-300 mg / jour.

Caution, for kidney and/or liver insufficiencies, it is not advisable to consider glutathione supplementation. Patients with bi-polar disorders may also be more sensitive and respond poorly to excess glutathione. Also be careful with people whose zinc level is low, taking glutathione decreases the blood level.

It is possible to naturally increase glutathione levels by eating lots of cabbage. Milk thistle, taken as an infusion or food supplement in the form of silymarin (its active ingredient), also helps to maintain a good level and prevent liver side effects.

[1] Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004;134(3):489-92

[2] Viña J, Sastre J, Anton V, Bruseghini L, Esteras A, Asensi M. Effect of aging on glutathione metabolism. Protection by antioxidants. EXS. 1992;62:136-44

[3] Homma T, Fujii J. Application of Glutathione as Anti-Oxidative and Anti-Aging Drugs. Curr Drug Metab. 2015;16(7):560-71

[4] Zhang C, Rodriguez C, Spaulding J, Aw TY, Feng J. Age-Dependent and Tissue-Related Glutathione Redox Status in a Mouse Model of Alzheimer’s Disease. Journal of Alzheimer’s disease : JAD. 2012;28(3):655-666

[5] Tong J, Fitzmaurice PS, Moszczynska A et al., Do glutathione levels decline in aging human brain? Free Radic Biol Med. 2016;93:110-7

[6] Souza DG, Bellaver B, Bobermin LD, Souza DO, Quincozes-Santos A. Anti-aging effects of guanosine in glial cells. Purinergic Signalling. 2016;12(4):697-706

[7] Watson SN, Lee JR, Risling TE, Hermann PM, Wildering WC. Diminishing glutathione availability and age-associated decline in neuronal excitability. Neurobiol Aging 2014;35(5):1074-85

[8] Stio M, Iantomasi T, Favilli F, Marraccini P, Lunghi B, Vincenzini MT, Treves C. Glutathione metabolism in heart and liver of the aging rat. Biochem Cell Biol. 1994;72(1-2):58-61

[9] Abdel Shakor AB, Atia M, Alshehri AS, Sobota A, Kwiatkowska K. Ceramide generation during curcumin-induced apoptosis is controlled by crosstalk among Bcl-2, Bcl-xL, caspases and glutathione. Cell Signal. 2015;27(11):2220-30

[10] Circu ML, Yee Aw T. Glutathione and apoptosis. Free radical research. 2008;42(8):689-706

[11] Golbidi S, Botta A, Gottfred S, Nusrat A, Laher I, Ghosh S. Glutathione administration reduces mitochondrial damage and shifts cell death from necrosis to apoptosis in ageing diabetic mice hearts during exercise. British Journal of Pharmacology. 2014;171(23):5345-5360

[12] Cascella R, Evangelisti E, Zampagni M et al., S-linolenoyl glutathione intake extends life-span and stress resistance via Sir-2.1 upregulation in Caenorhabditis elegans. Free Radic Biol Med. 2014;73:127-35

[13] Sekhar RV, Patel SG, Guthikonda AP, et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. The American Journal of Clinical Nutrition. 2011;94(3):847-853

DISCLAIMER

The information on the present website does not constitute either directly or indirectly any medical advice. The provided information is intended to inform and is in no way a substitute for the direct relationship between a patient and a health professional. Under no circumstances the information on the website are likely to make up for consulting, visiting and diagnosis by a licensed healthcare professional. Said information should not be interpreted as ensuring the promotion any some molecules or medical products.

Long Long Life will not be held liable for any action or decision-making in relation to the information on this website.

Long Long Life does not guarantee by any means any result following the implementation of the published information on the website herein.

Self-medication can be dangerous for your health, please seek medical advice before starting any treatment.

Dr. Marion Tible

Marion Tible Long Long Life

Author/Reviewer

Auteure/Relectrice

Marion Tible has a PhD in cellular biology and physiopathology. Formerly a researcher in thematics varying from cardiology to neurodegenerative diseases, she is now part of Long Long Life team and is involved in scientific writing and anti-aging research.

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Marion Tible est docteur en biologie cellulaire et physiopathologie. Ancienne chercheuse dans des thématiques oscillant de la cardiologie aux maladies neurodégénératives, elle est aujourd’hui impliquée au sein de Long Long Life pour la rédaction scientifique et la recherche contre le vieillissement.

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Why we need motor proteins for anti-aging autophagy

Long Long Life protéines motrices autophagie microtubules fibroblastes thérapie anti-âge

Why we need motor proteins for anti-aging autophagy

Cytoplasm motor proteins, an essential anti-aging ingredient for autophagy

Autophagy is a cellular process that cleans the cell of defective proteins, lipids and organelles. This phenomenon is part of a set of mechanisms that all participate in proteostasis, i.e. the balance of the entire protein network. Loss of proteostasis is one of nine causes of aging, leading to age-related diseases such as Alzheimer’s disease, Parkinson’s disease or cataracts[1]. Autophagy is effective thanks to two types of cellular compartments, the autophagosomes which trap and store a fragment of cytoplasm to eliminate, and the lysosomes which destroy the contents of the autophagosome. The loss of autophagic capacity with age contributes to the loss of functional capacity of the cells of older organisms[2].

What role do motor proteins play in autophagy?

For the lysosomes to degrade the contents of the autophagosomes, the two compartments must merge. This fusion is achieved by their meeting in the cell, in the perinuclear region (near the nucleus) in most cases[2]. In order to move within the cell, the autophagosomes and lysosomes follow the network of microtubules, small tubulin tubes, which allow transport into the cytoplasm. These are small motor proteins, the best known being kinesins and dyneins, which can, thanks to what resembles small molecular feet, move autophagic compartments along microtubules[3]. Positioning autophagosomes and lysosomes correctly in the same cell region is a decisive step in achieving autophagy. The biogenesis of autophagosomes and their degradation by lysosomes decreases with age but the mechanisms underlying this damage are not well known[2].

Long-Long-Life-motor proteins-autophagy-anti aging therapy-300x226

A Franco-American team of researchers recently published the results of a study[2] to understand the phenomena behind the decline in age-related autophagy. They were particularly interested in the positioning of autophagosomes and lysosomes within the cell, by comparing the movements of these organelles in fibroblasts of young (4 months) and elderly (24 months) mice. The researchers identified differences in the positioning of these compartments between young cells and elderly cells[2]. They then turned their attention to the molecular causes of this difference. Using a genetic approach, scientists mimicked the low amount of KIFC3, a motor protein of the same rank as dyneins and interacting with microtubules, as found in older cells. The results showed that a low level of this protein causes poor positioning of the lysosomes and therefore a decrease in autophagic capacity[2].

Motor proteins as therapeutic anti-aging targets

Autophagy is a mechanism of cell protection against senescence and cell death. When autophagy is effective, it fights aging and has been correlated with longevity in many studies. However, with age, this phenomenon declines, and the molecular mechanisms that are at its origin are still very little characterized. The positioning of autophagosomes and lysosomes near each other is very important to allow their fusion and degradation of defective compounds. The study showed that a bad placement of these entities in the same cellular region is a phenomenon found with age. This defect reduces the effectiveness of the autophagy. The loss of intracellular traffic of autophagous organelles is believed to be due to the decrease in motor protein levels allowing movement of lysosomes and autophagosomes along microtubules. This experiment identified motor proteins as new targets for future therapies that will aim to correct the loss of autophagy in the fight against aging and for longevity.

Anne Fischer

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Author

Auteur

Anne is studying medicine science at the Institute of Pharmaceutical and Biological Science in Lyon and she has graduated with a Bachelor’s degree in molecular and cellular biology at the University of Strasbourg.

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Anne étudie les sciences du médicament à l’Institut des Sciences Pharmaceutiques et Biologiques de Lyon. Elle est titulaire d’une licence en biologie moléculaire et cellulaire de l’Université de Strasbourg.

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References :

[1] Carlos Lopez-Otin, Maria A. Blasco, Linda Partridge, Manuel Serrano and Guido Kroemer. The Hallmarks of Aging, Cell 153, June 6, 2013, 1194-1217. http://dx.doi.org/10.1016/j.cell.2013.05.039

[2] Bejarano E, Murray JW, Wang X, et al. Defective recruitment of motor proteins to autophagic compartments contributes to autophagic failure in aging. Aging Cell. 2018;e12777. https://doi.org/10.1111/acel.12777

[3] Anna Akhmanova and Michel O. Steinmetz. Control of microtubule organization and dynamics: two ends in the limelight, NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 16 | DECEMBER 2015, 711-726.

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