Chapter 9
Why Do We Age? — Part 3
But exceptional longevity is a rare trait – in a sample of 5,000 in the US, only 1 person will be a centenarian; only 1 in seven million is a super-centenarian (age 110+ years). Impressively, siblings of centenarians are more likely to live to 100 than others born in the same year. Therefore, genes play a big role in super-ageing and we have already identified some of these genes, such as DAF2. Many of the genes associated with exceptional longevity are involved in regulation of blood sugar and food metabolism, and in the cell’s energy production and metabolic rate. You will appreciate the enthusiasm to understand whether we can manipulate these genes to try to reduce the frequency of health problems in latter years for all of us. But let’s return to ‘environmental’ factors and ageing. You will be aware of the expression ‘you wear your heart on your sleeve’. Well, when it comes to ageing, you wear your age on your face! The ageing face is a good illustration of our cells ageing. Facial skin cells and tissues exhibit all of the hallmarks of ageing and are there for all to see. My mother believed that you could tell a smoker by their skin because smoking speeds up the pace of ageing. Another recent twin experiment has proven her to be correct. Researchers in Ohio recruited nearly 200 sets of identical twins who were attending an annual twin festival. Using photographs of each twin set, the researchers asked an independent panel to rate differences in the twins’ appearances, to decide whether they thought one twin looked older than the other and to guess their age. They found several factors influenced appearance and facial ageing, including smoking and excessive sun exposure – 10 years of smoking added 2.5 additional years of ageing to a twin’s face, compared with a twin who didn’t smoke. Stress also influenced the panel’s interpretation of the photos: divorced twins looked two years older on average than a twin who was married or widowed. Twins taking antidepressants also looked older – possibly because depression itself increased facial ageing or because use of antidepressant drugs relaxed facial muscles in a way that increased the appearance of ageing. Facial ageing and body weight were also linked. A heavier body weight before the age of 40 was associated with an older appearance. However, in women over 40, a heavier body weight was associated with a more youthful look, compared to a thinner twin. I recall listening to an interview with the actress Kathleen Turner over a decade ago in which she claimed that ‘after a certain age’ we should sacrifice a bit on the hips for the sake of the face – a view that seems to be backed up by this research. So lots of external factors other than genes contributed to an older appearance in identical twins. Every cell has one nucleus.
Chapter 2: Why Do We Age?
The nucleus is the cell’s ‘library’ and gives instructions for all of the cell’s activities, including everything that regulates ageing. The nucleus houses our chromosomes, which hold our genes and therefore our DNA, dictating everything that we are. DNA is responsible for the division of our cells throughout life. Each cell has 46 chromosomes, made up of protein and a single molecule of DNA. Our liver cells only use the ‘liver DNA’, the rest is switched off. Our eyes only use the ‘eye DNA’, etc. At each end of a chromosome is a telomere, often compared to the plastic tip at the ends of a shoelace. Telomeres are a hot topic in gerontological science because they protect the chromosomes, preventing them from unravelling, sticking to each other or changing shape. Damaged chromosomes cannot efficiently send messages from the nucleus to other cell structures. Each time a cell divides (replication), the DNA separates in order for the genetic information to be copied. When this happens, the DNA coding is duplicated – with the exception of the telomere, which is not. When the copy is complete, the copy separates from the original at the telomere. As such, with each cell division, the telomere gets shorter and shorter until it can no longer completely protect the chromosome. It is then that the cell dies. We use the length of a telomere to determine the age of a cell and how many more divisions remain for that cell. Hence the gerontological interest in telomeres. Ageing is characterised by break-up of sections of the chromosomes in the nucleus, which disrupts transfer of vital information from the nucleus or ‘library’ to the rest of the cell. Therefore, the instructions from the nucleus become flawed. These instructions include information on replication of the cell, production of energy and removal of waste materials. Flawed information results in slow functioning, inefficient operation and, eventually, the death of a cell.
Chapter 2: Why Do We Age?
In the end, all of our cells are ‘mortal’ with the exception of one cell type – cancer cells. Unlike normal cells, cancer cells do not undergo programmed cell death but continue to multiply without end. Therefore, they eventually take over all other cells and body organs, this is what we know as metastases. Cancer cells show no telomere shortening which may be the very reason for their survival. A better understanding of telomere survival in cancer cells may help us to manipulate telomere shortening in normal cells and thereby delay ageing. At present, we cannot manipulate human genes or human telomere length. But it’s a different story for mice genes.
It is possible for scientists to manipulate the breakdown of chromosomes in mice to make cells younger. This discovery won the Nobel Prize in Physiology or Medicine for Shinya Yamanaka in 2012. He was able to turn mature cells into young cells that had the capacity to change into a number of different cell types – these cells are known as pluripotent cells. The early human embryo consists mainly of these pluripotent cells, which may become a nerve cell, skin cell, heart cell or liver cell and start the growth thereafter of that organ-system in the embryo. Shinya Yamanaka succeeded in identifying a small number of genes in mice that regulate transition from mature to pluripotent cells. When these genes were ‘switched on’, skin cells could be reprogrammed as immature pluripotent cells, meaning they could grow into the cell type of the scientists’ choosing. This major discovery holds great potential for future manipulation of ageing as well as for developing new approaches to organ transplants.
Chapter 2: Why Do We Age?
Proteins that function as recycling trucks to take the waste and toxins from within cells to recycling centres in the cell and beyond are also switched on and off by instructions from the nucleus. In animals genetically engineered to produce higher levels of these proteins, lifespan is extended by 30 per cent. This is remarkable. The average male in the Western world lives to 80. Should we be able to manipulate these ‘recycling’ proteins, lifespan would increase such that the average would be 105. The oldest man in the UK is 111 – he could be 141 if we were able to manipulate these proteins. Many age-related diseases occur because of an inability to clear the waste fast enough through the cells by the recycling trucks – diseases such as arthritis, heart disease, cancer and dementia. The clearance process that cells use to destroy and recycle cellular waste is known as autophagy. Research in this area won Yoshinori Ohsumi, a Japanese cell biologist, the 2016 Nobel Prize in Physiology or Medicine. Ohsumi discovered how autophagy works and its relevance to ageing. Work is now focusing on ways to manipulate autophagy in order to extend healthy lifespan. Another theory is that we are programmed to age, that each of us is programmed at birth to die at a certain age and this is down to the genes we inherit. In support of this theory is the lack of variation in lifespan within species. Elephants die at around 70, spider monkeys die at around 25 and humans die at around the age of 80.