Article curated by Ed Trollope
At the moment at least, ageing is an inevitable part of life. And yet scientists don't really understand how, or why, we age. It is thought that a combination of pre-programmed bodily changes and environmental issues are responsible, but how these interact isn't clear. Some researchers in this area aim to help us make better lifestyle choices in order to live a long and healthy life, while others look for a way to stop the aging process in its tracks.
One question that needs answering before we can fully understand the aging process is whether it is something coded into our genes, or simply a case of our bodies ‘wearing out’. From an evolutionary point of view, once an animal has passed reproductive age, it is of little use, and may not be worth the food needed to keep it alive. There have been some suggestions that human women live so long post-menopause because they were useful in helping to look after their grandchildren, allowing mothers to gather more food. However this benefit would not run to humans living as long as we seem to now. So some scientists argue that aging is purely a result of damage accumulating in our bodies - meaning that if we could prevent that damage, we may be able to extend our lifespans indefinitely.
One of the ways in which our bodies are damaged as we get older is down to the build-up of free radicals. Free radicals are produced as a normal part of metabolism, and are highly reactive, as they have an unpaired electron in their outer shell. This means they tend to interact with molecules in the body, and in doing so can cause a cell to die, or become cancerous. Free radicals aren't all bad - they are important for cells to signal and communicate with each other. If too many are produced, however, the body’s natural protective mechanisms can't handle the onslaught, and damage can occur. This is known as oxidative stress, and more of it builds up as you get older. Taking in extra antioxidants, from foods such as blueberries, is thought to help neutralise free radicals by providing them with the electron they need. However more research is needed before we can say for sure that consuming antioxidants can prevent cancer or extend life.
Throughout our lives, as we grow, change and heal, our DNA replicates itself, and cells divide. This is a difficult process, and each time it occurs, the very ends of each chromosome is missed. This would be really bad news if it meant that information was lost during each cell division, but luckily, nature has a solution. The end section of each chromosome is a telomere - a section of repeating nucleotides which protect the rest of the chromosome. After cell division, in some types of cell, such as stem cells, an enzyme replenishes the telomeres. However in the majority of cells it is not replenished and this limits the number of times the cell can divide. It is not known whether it is the act of the telomeres shortening that causes the symptoms of aging, but researchers are nevertheless keen to determine whether it is possible to replenish these sequences7. In some types of cell such as stem cells, an enzyme replenishes the telomeres after each division, meaning the cells can, in theory, live forever. Harnessing this ability may bring us one step closer to eternal youth.
While some scientists are trying to discover the common factors that cause all of us to age, others are wondering why it is that some people live to 100, or even more, despite not living particularly healthy lifestyles. It is likely that the difference is down to their DNA. We know that people react differently to different drugs and lifestyles, but isolating the genes responsible is a mammoth task. In many cases, it is a combination of genetics and environmental influences that leads to a particular disease developing. One day, genetic testing may lead to medicine personalised for each individual, and help us to live longer and healthier lives. Already, testing for genes linked with breast cancer allow at-risk individuals to take preventative measures, and the dosage of some drugs can be altered depending on a person's genetic make up. For the moment, however, for most diseases the days of personalised medicine is a long way off.
Even if it was possible to find a gene “responsible for” every disease, it’s still not that simple. Although all cells in our body (other than red blood cells) contain a full copy of our DNA, not all of it is used in each cell. The genes which make up our DNA tells cells how to make various proteins, so only the genes that carry instructions for making proteins the cell needs will be activated. How genes are regulated is complex, and isn't well understood. As well as internal factors, like what kind of cell the DNA is in, environmental factors such as diet have an influence. This area of research, known as epigenetics, has had a huge impact on our understanding of genetics. It shows that what's coded in our DNA is not the full story. Our lifestyle, and even that of our parents and grandparents, can influence which genes are turned on and so affect our health and how we age.2
As the search for the secret to eternal life continues, scientists have begun to turn to other animals for clues. Various different animals have been hailed as holding the secret to eternal youth. One of these is the naked mole rat, which lives in East Africa. Most other rodents of its size have short life-spans (a maximum of 4-5 years for mice and rats) but the naked mole rat can live for over twenty years. Scientists are trying to explain why they can live such a long time, but it may be due to their very low metabolism, and their ability to reduce it further during times of hardship. These periods could give them a chance to deal with oxidative stress more effectively, so their body would accumulate less damage than it otherwise would. They also seem to be hugely resistant to cancer - in fact, a naked mole rat with cancer has never been discovered. Mining the secrets of the animal kingdom may be our best bet in our fight to extend our healthy life-span.
As well as looking for animals that naturally live a long time, researchers have found artificial methods of increasing some animals' lifespans. For example, severe calorie restriction allowed mice to live 50% longer than normal. However these gains come at a price. The long-lived mice suffered from reduced fertility and flies bred to live longer don't reproduce as successfully their short-lived counterparts. When it comes to humans, while extending life may seem like a good aim, it wouldn't be so positive if it came at the cost of health. Trials like this are also very difficult to conduct on humans due to the safety risks involved, and the necessarily time-intensive nature of the trial required!
The social implications of extending human life are also of great concern. As people live longer, and the old outnumber the young, the question of how we pay for the older generations is raised. Retirement ages will need to rise with life expectancy, but that can only be feasible if the mental and physical problems that are associated with old age are defeated, so people can work for longer. Currently, researchers believe that human lifespan does have an upper limit, so life expectancy won’t just keep increasing indefinitely. What this age limit might be however, isn’t clear, and probably won’t become so for many years to come.
This article was written by the Things We Don’t Know editorial team, with contributions from Ed Trollope, Cait Percy, and Johanna Blee.
why don’t all references have links?
 Pizza, Vincenzo et al. "Neuroinflammation and ageing: current theories and an overview of the data." Reviews on recent clinical trials 6.3 (2011): 189-203. DOI: 10.2174/157488711796575577
 Shammas, Masood A. "Telomeres, lifestyle, cancer, and aging." Current opinion in clinical nutrition and metabolic care 14.1 (2011): 28. PMCID: PMC3370421 DOI: 10.1097/MCO.0b013e32834121b1
 Severin, FF, and VP Skulachev. "Programmed cell death as a target to interrupt the aging program." Advances in gerontology (Uspekhi Gerontologii) 22.1 (2009): 37. DOI: 10.1134/S2079057011010139
 Hawkes, Kristen et al. "Grandmothering, menopause, and the evolution of human life histories." Proceedings of the National Academy of Sciences 95.3 (1998): 1336-1339.
 Aruoma, OI. "Nutrition and health aspects of free radicals and antioxidants." Food and Chemical Toxicology 32.7 (1994): 671-683. DOI: 10.1016/0278-6915(94)90011-6
 Kaur, Charanjit, and Harish C Kapoor. "Antioxidants in fruits and vegetables–the millennium’s health." International Journal of Food Science & Technology 36.7 (2001): 703-725. DOI: 10.1111/j.1365-2621.2001.00513.x
 Epel, Elissa. "How “Reversible” Is Telomeric Aging?" Cancer Prevention Research 5.10 (2012): 1163-1168. DOI: 10.1158/1940-6207.CAPR-12-0370
 Slagboom, PE et al. "Genomics of human longevity." Philosophical Transactions of the Royal Society B: Biological Sciences 366.1561 (2011): 35-42. DOI: 10.1098/rstb.2010.0284
 Nunes, Tiago et al. "Familial aggregation in inflammatory bowel disease: Is it genes or environment?" World journal of gastroenterology: WJG 17.22 (2011): 2715. DOI: 10.3748/wjg.v17.i22.2715
 Yen, Tina WF. "Genetic Testing for BRCA Mutations Can Save Lives." Archives of Surgery 146.4 (2011): 479-480.
 Xie, Hong-Guang, and Felix W Frueh. "Pharmacogenomics steps toward personalized medicine." Future Medicine 2.4 (2005): 325-337. DOI: 10.2217/174105220.127.116.115
 Lillycrop, Karen A. "Effect of maternal diet on the epigenome: implications for human metabolic disease." Proceedings of the Nutrition Society 70.01 (2011): 64-72. DOI: 10.1017/S0029665110004027
 Pérez, Viviana I et al. "Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat." Proceedings of the National Academy of Sciences 106.9 (2009): 3059-3064. DOI: 10.1073/pnas.0809620106
 Seluanov, Andrei et al. "Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat." Proceedings of the National Academy of Sciences 106.46 (2009): 19352-19357. DOI: 10.1073/pnas.0905252106
 Weindruch, Richard. "The retardation of aging by caloric restriction: studies in rodents and primates." Toxicologic pathology 24.6 (1996): 742-745. DOI: 10.1177/019262339602400618
 Partridge, Linda, and Martin D Brand. "Special issue on dietary restriction: dietary restriction, longevity and ageing—the current state of our knowledge and ignorance." Mechanisms of ageing and development 126.9 (2005): 911-912 DOI: 10.1016/j.mad.2005.03.023
 Carnes, BA, SJ Olshansky, and L Hayflick. "Can human biology allow most of us to become centenarians?" The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 68.2 (2013): 136-142. DOI: 10.1093/gerona/gls142