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Research in Genetics, Evolution and Environment


Anti-Ageing: Health or Beauty?

By Claire Asher, on 7 July 2015

a guest blog by Jorge I. Castillo-Quan, written for the 2015 Write About Research Competition.

If you had not heard of the term anti-ageing you have not noticed spam emails, television advertising, and articles in magazines. The term anti-ageing has definitely permeated our society. Most scientists struggle to explain to their non-scientist friends what their research is about. When I tell my friends I study ageing and anti-ageing interventions, almost everyone has an idea of what that means. Or at least they think they do. Some people think I am developing the latest generation of creams that will make wrinkles disappear, or that I am finding remedies to prevent greying hair, or the solution that will avoid balding, or even make stretch marks go away. Those with more imagination, think I am trying to defeat death and make people immortal. However, none of these ideas are in any way close to what I do. I explain to them that I do my research on ageing using the fruit fly Drosophila melanogaster. Yes, I work with those little flies that lurk around your kitchen. If you are now thinking why on Earth are you studying fly ageing, I do not blame you. I thought this once too. The first thing you should know is that I am not interested in making immortal flies (though that could be cool!), nor is my aim to understand how flies age per se. The simplest explanation is that studying ageing in an organism that is less complex than humans is more convenient and faster. After all we share 60% of our DNA with the fly. Although we look very different more than half of our genes have a counterpart in the fly. Similar things can be said about the roundworm Caenorhabditis elegans which shares 40% of our DNA. But why use these organisms that seem so unrelated to us? They have shorter lifespans and show traits of ageing. For example, as worms and flies age, they lose their ability to move properly. Is true that we do not wiggle around like worms, or fly and climb as much as flies do, but these rather specific behaviours are controlled in similar ways by locomotor programmes, some of which are similar between species. Hence, we can use these as readouts of how quickly a worm or fly is ageing. Furthermore, worms in laboratories only live about 2-3 weeks, while flies about 3 months. If you were to compare these lifespans with that of the more traditional laboratory organism, the mouse, you will find that you would be able to complete over 10 survival experiments in flies while only completing one survival experiment using mice, that live around 3 years. Each organism has its advantages. Worms are transparent so you can look and examine how every organ is changing over time. But while they do have a semi-organised neuronal system, they do not have a proper brain. Flies do, and research studying the development and organisation of the fly brain has advanced our understanding of the human brain so much so that it has been awarded several Nobel prizes in Physiology or Medicine.


Having established that flies are simpler than mammals like us and mice, and that they are relatively short-lived, the question remains, how am I developing the latest generation of anti-ageing creams using Drosophila? I have to be honest here and say that I am not working on this. Although the term anti-ageing is more commonly associated with these kind of interventions this is not the aim of my research. I study ageing to try to understand its biological principles and what drives it. I am sure that you thought that this is exactly what the multi-million anti-ageing industry is doing, but no. Although some (very little) of what is going on in the big wide world is labelled as scientifically proven, it is not. Or not at the standard that is required for prescription pills and creams you get from your GP or other health professionals. The anti-ageing industry as we know it is not regulated and is merely cosmetic. When biogerontologists (biologist studying ageing) talk about anti-ageing, we talk about physiology (function), health and disease. I try to study ageing to improve health during old age. Ageing is the major risk factor for many of the killer diseases of our time, like diabetes, cardiovascular disease and cancer. Understanding what makes aged bodies vulnerable to threat of these diseases should be a major concern of our generation. As our societies are growing older it is expected that our health systems will be overwhelmed with treatments for patients suffering from these chronic conditions. No hospital running on public funds will see you for wrinkles or stretch marks when you are 65, but they certainly have to see you for a growing lump, forgetfulness, urinary problems and other serious health issues.

Using model organisms like flies and worms we have been able to establish that specific genes have the ability to enhance longevity and health when appropriately manipulated. For example, the first genetic manipulations that showed that an organism could live healthier for longer came from research using worms. Later it was shown that the same interventions in flies and mice had similar effects and these organisms also lived healthier for longer. Nowadays, we have a more comprehensive understanding of what genes need to be manipulated to delay deterioration with age and, in some cases, even prevent the onset of diseases. Of course all of this is in worms, flies and mice. To jump to humans, interventions need to be less of the genetic kind and more on the drug side. With our current knowledge of ageing we are now trying to find ways to manipulate the function of genes with drugs. The good news is that it seems that this is possible. We do not need to manipulate the genes of an organism to delay the ageing process; this can be achieved by supplementation with specific compounds at specific doses, and in some cases at specific time of life. However, for humans to be able to take these anti-ageing interventions they need to be appropriately tested and regulated by agencies in charge of ensuring their safety for human consumption. We must continue to wait patiently…

For far too long we have considered growing older as two extremes, either as a burden to society, or as the great achievement of our generation. After all living to a 100 was quite rare 100 years ago. We should celebrate our older population and the best way is by enhancing their health and allowing them to live a fulfilling life, not one of deterioration and despair.

Next time you see an anti-ageing cream, think about this: would I rather have beauty or health? If the latter is your choice, just wait a little bit longer, we are working on it.


  • Juengst ET, Binstock RH, Mehlman M, Post SG, Whitehouse P. Biogerontology, “anti-aging medicine,” and the challenges of human enhancement. Hastings Cent Rep. 2003 Jul-Aug;33(4):21-30
  • Partridge L. The new biology of ageing. Philos Trans R Soc Lond B Biol Sci. 2010 Jan 12;365(1537):147-54
  • Rose MR.Can human aging be postponed? Sci Am. 1999 Dec;281(6):106-11
  • Stipp D. A new path to longevity. Sci Am. 2012 Jan;306(1):32-9

JorgeCastilloQuanJorge graduated with a Medical degree from the Autonomous University of Yucatan, Mexico. After this he completed an MSc in Clinical Neuroscience at the UCL Institute of Neurology, and a PhD in Genetics, Neuroscience and Biogerontology from the UCL Institute of Healthy Ageing (IHA). Currently he works as a Research Associate at the UCL IHA and Research Department of Genetics, Evolution and Environment.

Watch Jorge’s TEDx talk elaborating on the topic:

“Anti-Ageing: Beauty or Health?”

Go with your Gut:
How Gut Bacteria Influence Health and Ageing

By Claire Asher, on 9 July 2013

Inside the human gut is a thriving community of bacteria, many of which provide nutrients in exchange for a safe place to live. But they are not merely passive inhabitants – these microbes can also impact upon our metabolism. GEE researchers in the Institute of Healthy Ageing have been investigating how gut bacteria interact with medicinal drugs to influence lifespan and health.

The Nematode Worm,
Caenorhabditis elegans

There are 100 trillion microorganisms inhabiting the human gut – outnumbering human cells ten to one. These microorganisms are generally harmless, and in fact many are beneficial, forming a symbiotic relationship with their host. Occasionally, this relationship is less friendly, however, and gut bacteria can sometimes cause illness. Whether beneficial or harmful, gut bacteria can alter metabolic processes and chemical signalling pathways in the host, and recent research by Filipe Cabreiro, Catherine Au, David Gems and colleagues suggests gut microorganisms may interact with medicines to effect health and ageing.

Metformin: Beneficial Side Effects in Diabetes Treatment
A drug called Metformin is the most commonly prescribed treatment for type 2 diabetes, but it has long been noted that Metformin has some positive effects beyond those it is prescribed for, including reducing the risk of cancer. Metformin has also been found to slow the ageing process in rats and the nematode worm, Caenorhabditis elegans. This is partly mediated through Metformin’s effect on an enzyme, AMP-activated protein kinase (AMPK), which is important in influencing several key signalling pathways which have a knock-on effect on the ageing process. However, this is not the whole story – in nematodes Metformin also influences health and ageing through an interaction with microbes in the gut.

The Bacterium, Esterichia coli

Using a combination of techniques, including liquid-chromatograph mass spectrometry (LCMC) to visualise folate composition, and mutant E.coli strains and nematode worms lacking key metabolic cycles, Cabriero et al showed that E.coli are a critical aspect of the anti-aging properties of Metformin. The nematode, C.elegans, usually feeds on E.coli, but some of their microbial diet manages to avoid digestion and stick around in the nematode’s gut. Although the microbes aren’t really welcome there, and ultimately contribute to the worm’s death, they inadvertently have some beneficial effects during their stay. Worms reared on an E.coli-free diet do not show the usual positive effects of Metformin – in fact, without E.coli, metformin is toxic to the nematode. The researchers were able to track this bacteria-drug interaction to the B-vitamin, folate. Metformin substantially altered the folate content of E.coli, and when the researchers created a mutant strain of E.coli that lacked the ability to metabolise folate, nematode hosts experienced the same toxic effects were seen as when nematodes lacked the gut-bacteria entirely.

Interactions Between Host and Guest
So, metformin alters the folate cycle in the gut bacteria of nematode worms, and this in turn influences ageing in the worm. But how? There were no changes in the folate levels of the nematode worms treated with Metformin, indicating there must be another step in the process. This step appears to be mediated by methionine, an amino acid which is an important part of the nematode’s diet, obtained almost entirely from its gut bacteria. Metformin, by altering the folate cycle, reduces methionine production in E.coli, and this seems to be responsible for the anti-ageing effects on the worm host.

Metformin, Dietary Restriction and Ageing
Metformin, in interaction with the gut-bacteria, seems to mimic the effects of dietary restriction – the well-documented but still relatively poorly understood phenomenon by which reducing food intake increases lifespan. Anti-aging effects of dietary restriction have now been documented in rats, worms, and monkeys, and some people have even made the decision to reduce their food intake in the hopes that it will extend their lives. Research into the mechanisms by which dietary restriction is able to increase lifespan is on-going, and is a major focus of research in UCL’s Institute of Healthy Ageing. It is currently thought that dietary protein (and amino acids) may be important in controlling the effects of dietary restriction on ageing, and several chemical signaling pathways, including those regulated by AMPK, have been implicated in this process.

Thus, the anti-ageing properties of Metformin appear to be two-fold. By activating AMPK, Metformin may mediate life extension through its influences on key signalling pathways, essentially mimicking dietary restriction. Secondly, Metformin alters folate metabolism in microbial symbionts, reducing methionine production and again mimicking a restricted diet. Importantly, in the absence of the gut microbes, the drug showed strongly toxic effects, indicating that in some way, E.coli is able to ameliorate the drug’s toxicity. The effect of the drug Metformin is the result of a complex interplay between both toxic and beneficial effects on the host and the gut microbiota. Finally, all of this appears to interact with the diet of the nematode – feeding nematodes on a high-sugar diet eliminated the positive effects of Metformin.

Our gut bacteria are not passive hitch-hikers, but instead interact with our metabolic processes and dietary intake in complex ways. The effects of medicine can be strongly dependent upon our gut microbiome, and understanding this may help us to understand why the same drugs have different effects on different people. Drugs chosen for one beneficial effect may also have other, unintended effects (both positive and negative), but the extent and type of these may be heavily dependent upon our diet and gut bacteria. By viewing our bodies as a complex ecosystem of human cells interacting with a large and varied microbial population, we can gain greater insights into the workings of our bodies, and how to improve our health and lifespan.

Original Article:

() Cell 153: 228 – 239

This research was made possible by funding from the Wellcome Trust, The European Union and the Medical Research Council.

How Energy Shapes Life: Our Mitochondrial Partners

By Claire Asher, on 21 June 2013

Every cell in our bodies is a collaborative effort. A collaboration that dates back to just after the dawn of life itself, and marks one of the deepest divides in the tree of life. This symbiosis has had remarkably far-reaching effects, and is now thought to be key to understanding sex, ageing and death. The symbiotic entity in question is the mitochondrion; the power house of the cell. Biologists are increasingly realising the centrality of energy in understanding life, and a special issue of Philosophical Transactions of the Royal Society, introduced by Nick Lane, focuses on the synthesis of energy, genes and evolution.

Mitonucleus in Blue
Artwork by Odra Noel www.odranoel.eu
Image Used with Permission

Around 1.5 billion years ago, a simple, single-celled bacterium engulfed another one. But it didn’t eat it. Instead, the two cells started working together, and over the following millennia developed a cooperative relationship that laid the foundation for multicellular life and for diversification on a scale never seen before. This symbiotic relationship founded a new type of life – the eukaryote. Unlike their prokaryote ancestors, the eukaryotes had a special advantage: they now had internal membranes. This enabled them to generate energy more efficiently, utilising a force generated across a membrane, known as the proton-motive force. This allowed them to support bigger cells, a wider variety of diets, and ultimately led some eukaryotes to group together into multicellular, sexual organisms such as plants and animals.

Hand Over Your Genes!
Since mitochondria originated as free-living single celled organisms, they came complete with their own genetic information. As the cooperative partnership between the eukaryote host and its mitochondrial partners developed, the majority of these genes were transferred to the nuclear (host cell) genome. Bizarrely, though, a few genes remained with the mitochondria. In fact, the same few genes stayed put in almost all eukaryotes, even though this process happened many times independently. So what is so special about these genes? Why keep them in the mitochondria when it is costly to do so?

A Mitochondrion

A Rapid Response System
It is thought these genes remain in the mitochondria because they are needed there to allow individual mitochondria to respond rapidly to changes in the energy demands of the cell. When mitochondria are out-of-sync with their surroundings, they start generating dangerous ‘reactive oxygen species’ (ROS), also known as free radicals. Free radicals are famous for causing cancer, and this is because they act as mutagens, causing changes to DNA they encounter. Mutations caused by ROS can cause all sorts of problems, not just cancer, and many of the diseases of old age are thought to be caused by ROS mutations.

So, we need to keep a small set of genes – those that code for key components of the respiratory chain that generates energy in mitochondria – in close proximity to their site of use so that they can quickly respond to the ever-changing cellular environment. This is also true for chloroplasts in plants, and recent research by Puthiyaveetil and colleagues in GEE lends support for this explanation. They have found evidence for a chemical partnership, unique to eukaryotes, which may be important in regulating chloroplast function to minimise ROS production.

Both mitochondria and chloroplasts have held onto a few genes in order to allow a rapid response to changes in demand. Trouble is, by keeping those genes there, they are vulnerable to attack from any free radicals that are generated. Mutations in these genes can often cause the production of more free radicals, causing a downward spiral that eventually leads to the death of the cell.

Unusual Inheritance


Mitochondrial genes are not inherited in the same way as normal nuclear genes. The majority of our genes (residing in the nucleus) are inherited biparentally, that is, we inherit half from our mother and half from our father. Mitochondrial genes, on the other hand, are inherited only in the maternal line, through the egg. Mitochondria are also present in sperm cells – they have to be, since they are crucial for providing energy to power all that intense swimming – but sperm mitochondria are killed shortly after fertilisation. Recent research by John Allen in GEE suggests that uniparental inheritance of mitochondrial genes relates back to those pesky free radicals.

In sperm cells, mitochondria are working overtime to make sure the sperm has the energy to swim and find the egg. In the process they are churning out free radicals, and damaging the mitochondrial DNA. The mitochondria inside sperm start to suffer from the ravages of old age. But we don’t want to pass on old mitochondria to our offspring. It seems evolution has found an elegant solution – switch off the mitochondria in egg cells and pass these young mitochondria on to your offspring. De Paula and colleagues looked at the mitochondria in eggs, sperm and the bell of moon jellyfish (Aurelia aurita) and found egg mitochondria were largely inactive and simple in structure. Egg mitochondria also showed reduced levels of gene expression, an almost non-existent membrane potential and produced no free radicals, indicating that they were not actively generating energy. Eggs don’t need that much energy compared to sperm, and they can borrow what they do need from other cells. By switching off the mitochondria in eggs, and making sure these are the only ones passed on to the next generation, eukaryotes can reduce the build-up of harmful age-related mutations in mitochondria from generation to generation.

The Moon Jellyfish (Aurelia aurita)

Energy, Mitochondria and the Meaning of Life
The generation of energy is central to life. Mitochondria generate energy in all eukaryotic cells (animals, plants, fungi), and the symbiotic event that brought them into the eukaryotic cell changed life on Earth forever. Mitochondria proved massively beneficial, allowing eukaryotes to try new things, and ultimately produce the huge diversity of multicellular life we see today. However, housing another genome inside the cell came with nuances of its own, which led us to have sex, to age and die. Recent research in GEE highlights one way in which evolution has overcome one of these nuances – by switching off mitochondria in egg cells, offspring can inherit an undamaged copy, and because of this, ageing is not heritable. Other research in plants is broadening our understanding of why these genes are stored inside the mitochondria and chloroplasts in the first place. Throughout a plethora of different disciplines, mitochondria are proving crucial to understanding the fundamentals of life.

Original Articles:

() Philosophical Transactions of the Royal Society B

() Philosophical Transactions of the Royal Society B

Introduction to the Special Issue:

() Philosophical Transactions of the Royal Society B

This research was made possible by funding from the Natural Environment Research Council (NERC) and the Leverhulme Trust