Ageing
What are the scientists really looking at when they study ageing? Is their ultimate goal to resolve one of the oldest quests in the world and find the fountain of youth and immortality? Or are they perhaps on a more ethical quest, that of maintaining good health in old-age?
Longer life
Living better longer
Curing degenerative diseases linked to old age
Examples of animal research into ageing
Longer life
A study from last May came relatively close to the idea of the fountain of youth thanks to animal experiments. Injecting old mice with the blood of young mice produced a marked improvement in their activity, strength and cognitive power. It restored the brain to a younger, more plastic state, and the body to a more fit condition (1,2) The restorative effect of blood isn’t recent news, athletes used oxygenated blood to enhance their performances and back in time popes and monarchs wondered if drinking the blood of the young might improve their valour in battle, or their longevity. Maybe vampires had it right, well apart from the blood sucking part. Nonetheless, the possibilities are clearly sensational.
In the quest for longer life, scientists led by Hinco Girman of Stanford University in California tried to find the gene for increased longevity. However, sequencing the genome of centennials didn’t come to any conclusions (3) as only 30% of time’s effect on our bodies is genetic and the rest is left to life choice. On the other hand, the use of certain drugs was proven to be useful. Rapamycin, developed as an anti-ageing drug for transplant patients, has recently been shown to extend the lifespan of mice by 10% and rejuvenate their bodies.
As organisms age, inflammation can increase - linked to many disorders – and cell processes decline in efficiency. Rapamycin acts on a protein that is involved in cell growth and has an anti-inflammatory impact on the body. It also turns up autophagy which permits the cell to dispose of the waste that builds up inside it. Rapamycin is currently being tested in pet dogs and (unofficially) onhumans, possibly protecting them against diseases of old age such as cancer and heart conditions. (4) If over the next few years it becomes apparent that we can push back the limits of longevity by finding ways to slow ageing and even reverse it, we will enter a new moral paradigm
But before that perhaps we should be asking ourselves, isold age all that bad? Contrary to previous thoughts, ageing brains have been shown to be somewhat malleable and plastic and they are capable of much more connections between the left and rights hemispheres during thought processes. The older brain can even be better at some tasks - they are better at regulating or controlling their emotions, are just as good at forming impressions of others and their social and emotional abilities are very well preserved. (5).
Living better longer
However, the idea is not to live forever, but to match health span more closely with life span: improve the quality of life being lived. A new survey published in Nature Neuroscience suggests that chocolate might help brain function in 50-70 year olds. Elderly people given chocolate with high levels of flavinol, a naturally occurring antioxidant in plants, scored better on cognitive tasks and showed more activity in a region of the brain linked to memory – equivalent to scores of people 20 to 30 years younger. Epicatechin, a specific flavanol, may have antioxidant and anti-inflammatory effects that protect the inner walls of blood vessels, widening them and keeping the lining smooth, increasing blood flow. Chocolate would in a sense decrease blood pressure and risks of stroke. That would be perfect considering that Brits eat on average 10kgs of chocolate per year. Unfortunately, we would need a lot of commercial chocolate to get the right dosage of flavinol! (6)
Signs of ageing can also be postponed in mice placed on a high fat diet. As we get older, defects begin to develop, the DNA repair system becomes less efficient and risks of neurodegenerative diseases increase. The brain is in constant need of fuel in the form of ketones and sugars. When the body needs sugar, it breaks down fat and in the process makes ketones. By fuelling the brain with a rich fatty diet, researchers see a positive effect on signs of ageing. In a mouse model for cockayne syndrome where the mouse has rapid ageing due to the DNA repair system being constantly active whichdrains metabolic resources that then causes the cells to age really quickly, giving a high fat diet has a really positive effect. The brain cells are given sufficient extra metabolic fuel to keep the system running at full speed, even if it’s 'on' all the time. (7)
Life span can be associated with the cellular genetic ticking clock: telomeres. These are repetitive sections at the end of chromosomes that get shorter each time the cell divide and determine how quickly a cell ages. Longer telomeres are thought to protect us from ageing. Several factors can be linked to the shortening or stabilisation of telomeres. A study found that people drinking 350 ml a day of fizzy sugary drinks showed signs of accelerated ageing and had DNA changes typical of cells 4.6 years older than they were. The telomeres were shorter, probably due to oxidative stress caused by the sugar rush. (8) However there can also be positive factors. Breast cancer patients that followed a meditation course or took part of a support group over as little as a 3 months period, had telomeres that stayed the same size. On the other hand, patients who didn’t go saw their telomeres shorten during the same time frame. Meditation can often be linked to lower stress levels and better moods which might explain the results. This is the first evidence of meditation affecting us on a cellular level, and preventing the ageing of the cells. (9)
Curing degenerative diseases linked to old age
Let’s not forget above all that the study of ageing will mainly help us cure the degenerative diseases and those linked to old age. Sometimes animal models can give unique insights into these processes. Kyoto University’s Primate Research Institute saw a macaque born with premature signs of ageing - the equivalent of Progeria in humans. Genetic studies are underway to try to understand the condition and hopefully find a way to help patients with equivalent conditions. (10)
Ageing is the most significant and universal risk factor for developing neurodegenerative disorders such as ALS, Alzheimer’s, Parkinson’s or Huntington’s diseases. The risks increase disproportionally with age. The quality of protective genes called molecular chaperones declines dramatically in the brain of the elder, healthy or not, but the decline is accelerated even more in neurodegenerative patients. A team from Northwestern University, Proteostasis Therapeutics Inc and Harvard have found 28 genes for molecular chaperones directly linked to age related neurodegeneration which act as biomarkers. They are early indicators of ageing and disease and targets for new therapeutics. Next, the scientists envision understanding the basis for the decline of these specific molecular chaperones and develop ways to prevent their decline. (11)
Recently a protein linked to ageing was also identified as a new target for controlling diabetes in mice. Sestrin 3, a stress-inducible protein that can have an antioxidant function, is linked to premature ageing and age-related diseases. It provides critical feedback regulations that adjust metabolic and oxidative stress responses in cells. A team from the Indiana University School of Medicine showed that the protein also controlled the production of glucose and insulin sensitivity in the liver, making also an important target for drug development for type2 diabetes. (12)
Overall, the study of ageing does more than just try to fulfil our dream of eternal life, it also permits us to find new ways to target and treat diseases linked to old age. It isn’t all about living for the rest of time but living better while we are alive, by finding ways to decrease degenerative disease common in the elderly and improving general health in the old and the young. It would certainly be nice if old age was healthier.
Advances in genetic, embryology and stem-cell research have already hinted at the huge possibilities in improving the human body. Thanks to age-linked studies, awful diseases are being treated but even so, medical practice must keep abreast of ethics and public consent before eternal life can be imagined. Moving from preventing diseases to tinkering with the life cycle of healthy but ageing people is close to the “step too far”. But the science as it is now is nowhere near that point although it does suggest we are on the threshold of a series of exciting breakthroughs.
Examples of animal research into ageing
11/07/18 Trial of anti-ageing drugs that rejuvenate immune system hailed a success
Scientists have hailed the success of a clinical trial which found that experimental anti-ageing drugs may protect older people from potentially fatal respiratory infections by rejuvenating their immune systems.
The drugs work by blocking a cascade of events in the body that starts with the so-called “mechanistic target of rapamycin”, or mTOR. This is one of a group of proteins involved in the ageing process. Tests in mice have shown that experimental mTOR inhibitors can extend lifespan and revitalise the immune system and organs which deteriorate in old age.
09/07/18 Apple peel drug makes mice live longer by targeting a cause of ageing
We’re beginning to understand the causes of ageing and how to reverse it – thanks to an extract from apple peel. A team has found that a combination of dasatinib – a leukaemia drug – and quercetin – an extract from apple peel – can make elderly mice live 36 per cent longer. These drugs were chosen for their ability to selectively kill so-called senescent cells. These abnormal cells are in the process of breaking down, but they resist dying.
30/05/18 Drugs that help our cells tidy up might extend lifespan
Boosting the body’s “disposal system” can stave off age-related organ damage and increase lifespan by 10 percent in mice. To find out if boosting the disposal system could slow ageing, Beth Levine at UT Southwestern Medical Center in Texas and her colleagues turned to mice with a genetic mutation that increases autophagy in the heart, liver, muscle and brain. They found that mice with this mutation live three months longer. “It might not sound like a lot, but in the mice it’s a 10 per cent increase,” says Levine.
24/11/16 Edible dormice: The older they get, the more they rejuvenate their cells
The shortening of telomeres in cells was thought to be an important biomarker for lifespan and ageing. The edible dormouse (Glis glis), a small hibernating rodent, now turns everything upside down. In contrast to humans and other animals, telomere length in the edible dormouse significantly increases in the second half of its life.
This could explain how this species can reach a maximum lifespan of 13 years, which is a Methuselah-like age for a small rodent.
http://www.vetmeduni.ac.at/en/infoservice/presseinformation/presseinformationen-2016/edible-dormice-the-older-they-get-the-more-they-rejuvenate-their-cells/
27/10/16 Naturally occurring compound extends mice lives
A compound called NMN, which can be found naturally in foods like Cabbage and Edamame, has showed beneficial effects when given to mice. Mice given the compound showed a boosted level of NAD, a protein which is believed to play a role in the ageing process. Mice who took the compound had a longer lifespan than the control group.
http://www.independent.co.uk/news/science/elixir-youth-discovery-broccoli-cucumber-cabbage-mice-humans-a7383411.html
28/06/16 Anti-ageing compound shows early success
An anti-ageing compound is to be put forward for clinical trials by Keio University (Japan) after promising results in mice. The compound nicotinamide mononucleotide (NMN) was shown to slow the natural declines of metabolism, eyesight and glucose intolerance in mice after stimulating sirtuin genes that have well documented life-lengthening properties.
http://the-japan-news.com/news/article/0003030620
22/06/16 The absence of a single protein spurs muscle aging in mice
One of the alterations that most affects the quality of life of the elderly is muscle wastage and the resulting loss of strength, a condition known as sarcopenia. At about 55 years old, people begin to lose muscle mass, this loss continues into old age, at which point it becomes critical. The underlying causes of sarcopenia are unknown and thus no treatment is available for this condition. A new study has discovered that Mitofusin 2 is required to preserve healthy muscles in mice. In the paper, which has been published today in The EMBO Journal, these researchers indicate that this protein could serve as a therapeutic target to ameliorate sarcopenia in the elderly.
4/02/16 Destroying worn out cells makes mice live longer
When cells wear out, they don’t always die. Instead, they can start pumping out a brew of compounds that can cause damage to surrounding tissue. The process, called senescence, is thought to protect us against cancer and help wounds heal. But as we get older, senescent cells start to accumulate across the body, and may be partly responsible for the general wear and tear of all our organs as we age. Elevated numbers of these cells have already been linked to heart failure, arthritis, Alzheimer’s – and cancer. Get rid of these cells and a host of benefits ensue, suggest mouse studies by Darren Baker, Jan van Deursen and their colleagues at the Mayo Clinic in Rochester, Minnesota.
04/12/15 Drugs may allow dogs to live for years longer
http://www.thetimes.co.uk/tto/science/article4631961.ece
29/11/15 World’s first anti-ageing drug could see humans live to 120
28/10/15 Asthma drug could rejuvenate ageing brains
A study in rats suggests that a cheap asthma drug may help rejuvenate ageing brains. A six week study showed that montelukast improved memory and learning in old rodents by reducing inflammation in the brain and encouraging the growth of fresh neurons. The study involved rats remembering wheee platforms in a swim test were located.
24/09/15 The worm sense of smell can predict when it dies.
Researchers have found a correlation between declining ability to smell and lifespan in worms. The worm has 12 pairs of specialized neurons in its brain that detect stimuli in the environment and researchers looked at how this circuitry of neurons changes with age as they lose their sense of smell. They found that communication between neurons become less active with age. If the signalling between neurons ends up being important in how organisms age then manipulating the nervous system may prove a fruitful way to minimize the effects of aging or rejuvenate brain functions.
http://www.sciencedaily.com/releases/2015/09/150918132611.htm?utm_source=dlvr.it&utm_medium=facebook
10/07/15 Male badgers who spent their youth fighting aged quicker than relaxed ones
Male badgers who spent their youth fighting aged quicker than relaxed ones. Those who don’t fight for a mate and compete prioritise ‘health and wellbeing’ and sex. The findings suggest that male badgers age faster than females because of the male-male competition they experience during their lifetime. This research sheds new light on why mend tend to live shorter lives – make love not war.
21/05/15 Young blood helps repair fractured bones of ageing mice
Young blood helps repair fractured bones of ageing mice. Once again the blood of young individuals seems to have a miraculous effect on older mice. (https://www.animalresearch.info/…/…/diseases-research/ageing/)Over the past years, researchers have reversed muscle atrophy, memory loss, heart degradation, cognitive decline and now bone degradation by pumping the blood of young mice into older animals. Fractured bones of old mice fixed themselves much faster if they received the blood from young mice and reversely, the young mice that received old blood had a slight decrease in the ability to repair the fractured bones.
http://www.newscientist.com/…/dn27562-young-blood-helps-rep…
19/03/15 Two new drugs delay ageing by clearing out senescent cells
Two new drugs delay ageing by clearing out senescent cells. Scientists have coined the term ‘senolytics’ to describe a new class of drugs designed to delay the process of ageing. The research focussed on senescent cells – cells we acquire throughout life that shut down, stop dividing and sit there being of little use. The older we get, the more of these cells we have. In a study in mice, two drugs were effective at eliminating these cells from fat tissues and bone marrow, consequently improving cardiovascular function and stamina, reducing osteoporosis and frailty and extending healthy lifespan. However, unless you replace senescent cells with healthy versions, after a few rounds of treatment, the process would probably become unsustainable. The idea is to harness the body’s own immune system to do what the drugs are doing and sweep out senescent cells but more gradually – the body would have time to replace them.
26/02/15 Stress shaves off telomeres in hyenas’ chromosomes
Stress shaves off telomeres in hyenas’ chromosomes. Being a low-ranking hyena is stressful – so stressful that even the chromosomes are affected. Telomeres, stretches of DNA at the tips of chromosomes that protect them from shortening during cell replication, are shortened by stress in low ranking hyenas. With increased stress, higher amounts of stress hormones and cellular by-products like oxygen ions and peroxides are produced, both of which have been shown to shorten telomeres in other species. When telomeres fall below a certain length, cells go into damage control mode and die. This study is the first to show that the stress of social hierarchy can shorten telomeres in a wild species.
23/01/15 Blocking a gene in mice helped them live 15% longer
Blocking a gene in mice helped them live 15% longer without any side effects. In humans, switching off that single gene could extend life by 12 years and make elderly people fitter. The gene Myc is important in cell division, growth and death, however, when it is over-active, it can cause cancer. Limiting the gene, on the contrary, extends life, makes the mice fitter, and prevents them from developing age related conditions. The mice have a healthier immune system.
22/01/15 blood of young mice brings new life to ageing organs - 1st human trials
By joining the circulatory system of an old mouse to that of a young mouse, scientists have shown that the blood of the young mice seems to bring new life to the ageing organs, making old mice stronger, smarter and healthier. Changes can be seen in the brain, spinal cord, muscles and almost every other tissue examined. Labs have started identifying the components in the blood responsible for these changes and for the first time in September, a clinical trial in California tested the benefits of young blood on older people with Alzheimer’s disease. The young blood seems to activate stem cells in the older mice which results in a variety of rejuvenation across organs and the growth of new cells – the organs appear younger.
http://www.nature.com/news/ageing-research-blood-to-blood-1.16762
29/10/14 Anti-aging drug extend life by 13% in female mice
A potential anti-ageing drug that has been shown to extend mouse lifespans by up to 13% (in females) could be set for a test in pet dogs. Rapamycin is regularly given to human patients as part of an anti-rejection drug cocktail after kidney transplants, but it’s effects on lifespan have not been tested in humans because human lifespans are so long. The proposed trial would be conducted using large dogs with a natural lifespan of eight to ten years, with the treatment beginning at six to nine years of age.
http://www.nature.com/news/pet-dogs-set-to-test-anti-ageing-drug-1.16237
03/10/14 immune system suppressant increases life by 14% in mice
A drug originally used to suppress the immune system for people receiving organ transplants was found to have life-extending properties for yeast and worms. Now testing on mice increased their life by up to 14% despite the fact the animals tested were equivalent to 60 years old people.
http://www.independent.co.uk/news/science/antiageing-drugs-may-have-been-developed-9771056.html
References
- http://www.theguardian.com/commentisfree/2014/may/05/blood-transfusions-rejuvenate-mice-humans
- http://www.nature.com/nm/journal/v20/n6/abs/nm.3569.html
- http://www.sciencesetavenir.fr/sante/20141113.OBS4960/super-centenaires-alors-ce-mythe-du-gene-de-la-longevite.html
- http://www.theguardian.com/science/2014/nov/08/anti-ageing-drugs-tested-on-dogs-cancer-heart
- http://theconversation.com/aging-brains-arent-necessarily-declining-brains-33574
- http://www.theguardian.com/lifeandstyle/2014/nov/02/is-chocolate-good-for-you
- http://www.sciencedaily.com/releases/2014/11/141105112614.htm
- http://www.theguardian.com/lifeandstyle/2014/oct/16/sugar-soft-drinks-dna-ageing-study
- http://www.sciencealert.com/world-first-evidence-suggests-that-meditation-alters-cancer-survivors-cells
- http://ajw.asahi.com/article/sci_tech/science/AJ201411040032
- http://www.news-medical.net/news/20141104/Scientists-uncover-small-set-of-genes-critical-in-aging-and-neurodegenerative-disease.aspx
- http://news.medicine.iu.edu/releases/2014/11/dong1.shtml
Last edited: 4 March 2021 13:47