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?
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.