Judith A.Davey 13/11/2020
In my previous post, when I looked at the social, health and economic benefits of the so-called “Longevity Dividend” I noted that this change could come about by delaying the biological processes of ageing and thereby extending the lifespan of the human species. And even if we make progress against specific diseases, the biological processes of ageing continue. All living things have biochemical mechanisms which influence how quickly they age, and we may be able to adjust these mechanisms, but how?
What is ageing?
“Ageing is commonly characterised as a progressive, generalised impairment of function resulting in increasing vulnerability to environmental challenges and an increased risk of developing disease.”
Why do we age?
The biological state of an organism reflects its capacity to regulate and repair many internal biochemical and biological processes as well as to deal effectively with the effects of the external environment. In humans, changes associated with ageing begin as early as the third and fourth decade and include a progressive reduction in the functioning of vital organs in the body, such as kidneys and heart. This process relates to molecular, cellular and physiological changes.
Over time there is a decline in the ability of an organism to maintain optimal and steady functioning. This involves changes in biochemistry, genetics, DNA and cellular replication. So far, there are no treatments or therapies that have been demonstrated to slow or reverse this process in humans.
Telomeres are specialised regions located at the end of the DNA sequence and act to protect the ends of chromosomes. As each cell renews itself there is a reduction in the length of the telomere. Although telomeres act to prevent uncontrolled and cancerous cellular division, telomere shortening contributes to the ageing process as the number of divisions that a cell may undergo is capped. Telomere length is not fixed and there is significant variation between individuals.
DNA defects also promote the ageing process. During a lifetime DNA will gradually develop damage through a wide variety of mechanisms and this damage will eventually lead to the dysfunction of genes, proteins and cells.
What about genetics?
Observational studies in humans have highlighted particular genes that are associated with exceptional longevity. In the natural world longevity genes have not been subjected to strong selective pressures, because, even if an animal possessed a longevity gene, the benefit would only be realised if the animal successfully escaped all causes of death (predators, disease etc.) or was reared in a protected environment. There has been little evolutionary pressure to select organisms possessing longevity genes and animals have typically allocated genetic resources to ensure reproductive efficiency instead.
It has, however, become apparent that there is a clear relationship between genetic make-up and the ageing process in humans. Longevity genes may act to increase the resistance of the cell to stress or improve its capacity to undertake genetic repair. Longevity genes can also affect various biochemical pathways and reduce the risk of age-related disease development. The children of centenarians have a significantly reduced incidence of diabetes and heart disease compared to age-matched controls, suggesting inherited genetic protection.
Human studies suggest that around 25% of the variation in lifespan is dependent upon genetic profile with the remaining 75% being related to external environmental influences. However, it has been found that more than 50% of decline in cognitive function in older age is determined by genetic factors.
Telomere length is also heritable. People with shortened telomeres are more likely to develop conditions such as atherosclerosis, vascular dementia and infections. If the genetic basis for telomere length can be accurately determined then it may become possible to manipulate telomere length to reduce the risk of developing age-related diseases.
As we grow older, the influence of environmental factors on our health becomes more important, and the influence of genetic factors less important. The environmental factors that accelerate ageing are those that influence cellular damage and repair. Prominent among these are environmental chemical toxins, such as asbestos, lead, mercury and smog particulates.
Only a small proportion of cancer arises from family history or genetics. Much more is related to environmental factors – smoking, poor nutrition, lifestyle choices – lack of exercise, diet, exposure to sunlight and toxins.
Studies of the ageing of identical twins, with identical genetic make-up, show that differences in visible ageing signs relate to personal lifestyle choices and habits. The most notable factors influencing degree of ageing are sun exposure and smoking. Other possibly contributory lifestyle factors are alcohol consumption, stress, diet, exercise, and medication. It seems that genetic influences on ageing may be overrated, with lifestyle choices exerting far more important effects on physical aging.
How to live longer – all to do with lifestyle
Overall, it seems that physical fitness is the single most important thing an older person can focus on to remain healthy and live longer. This should be accompanied by what we have all heard many times before – better nutrition and hygiene, improvements in health care, better accessibility to education and improved working life, and maintenance of function (social, physical, and psychological).
What else could help?
Caloric restriction (CR) involves a reduction in calorie intake whilst maintaining all the required nutritional substances. CR extends life span and retards age-related chronic diseases in a variety of species including rats, mice, fish and worms. Preliminary experimental results have also yielded promising initial results in primates.
Although there has been comprehensive development of medication and therapies that can reduce the incidence and development of age-related disease, there are no agents that comprehensively reduce cellular damage.
Research therefore suggest that the risk of developing age-related disease processes can be influenced by genetics and lifestyle change. It is the latter which is more likely to be achievable if we want to prolong life and improve its quality.
 Dr Lloyd Hughes, What influences how we age? https://www.gmjournal.co.uk/what-influences-how-we-age