We are born, we live, we age, we die. For millennia, this has been the natural order of human life. However, in the last 25 years, humanity has made massive strides in understanding, and importantly manipulating, the ageing process. The idea of ageing is now being challenged. Rather than viewing ageing as an inevitability, scientists are beginning to perceive it as a disease, one that could be treated, halted, or even reversed.
Most noticeably presenting as wrinkles and grey hair, ageing extends far beyond simply the aesthetic. In biological terms, ageing is characterised by the gradual decline in the functional capacity of cells and their associated tissues and organs. In practical terms, this is seen as a slowdown in physical and cognitive abilities.
The biology of ageing
Ageing is an intensely complex syndrome influenced by environmental, genetic, and epigenetic factors. As such, a myriad of possible influences has been described as part of the ageing process. These primarily include oxidative stress caused by the accumulation of reactive oxygen species, telomere shortening, and deoxyribonucleic acid (DNA)/histone methylation patterns. Let’s look at each in turn:
- Oxidative stress is caused by the cellular accumulation of free radicals and is contributed to by environmental factors such as diet, smoking, and air toxicity.
- Telomeres are the buffer regions of DNA that cap the ends of chromosomes and prevent chromosomal attrition during DNA replication.
- DNA/histone methylation governs what genes are repressed or expressed.
Age-related diseases, as the name suggests, are closely associated with ageing. These include type 2 diabetes, neurodegeneration and cancer, among many others. Despite such a broad range of pathologies, the commonality between them is the insulin response. Previous research by Cynthia Kenyon et al revealed that ageing and its related diseases can be influenced through genetic mutation or direct intervention (eg. dietary restriction) of the evolutionarily conserved insulin signalling pathway.
Can we extend human life?
Kenyon’s seminal 1993 paper demonstrated that specific mutation of the insulin signaling pathway in the Caenorhabditis elegans nematode worm yielded a mutant that lived twice as long as its wild-type counterparts. Similar results were later reproduced in Drosophila melanogaster fruit fly and Mus musculus mouse model organisms. These experiments demonstrated that the linkage between ageing and insulin was conserved up the evolutionary tree. The next logical hypothesis was whether the same could be done in humans.
Studies such as The Dutch Famine Cohort have shown increased resistance to age-related diseases in descendants of those who survived famines. This study suggested not only that there exists a similar insulin-age response in humans, but that it can be passed down from generation to generation through (epi)genetic memory.
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The effect of life extension on society
Cynthia Kenyon is currently the Vice President of Aging Research at Calico Life Sciences, a Google-subsidiary, focused on ageing. Calico demonstrates the interest of tech giants in addressing an area of healthcare with high unmet needs. But how would such life-extending treatments alter the fabric of modern society?
Already we are seeing demographic shifts in various countries in response to improved healthcare and higher standards of living. Major economies such as China, Japan, and the UK are all experiencing ageing and/or shrinking populations.
When developed, such life-extending treatments would only be accessible to wealthy people in wealthy countries, thereby exacerbating the trend of ageing populations that already afflicts many developed nations. This would lead to further concentration of wealth among older generations, placing even greater economic strain on the dwindling population of young people expected to provide for a growing number of dependent retirees.
The 2022 UN World Population Prospect report predicted that Sub-Saharan Africa would become the most populous region in the world by the late 2060s. As young generations reach working age, these countries will experience a significant economic boost. Governments of Western Europe and East Asia must plan how to address ageing populations to buttress their economies against developing demographic trends and ensure they remain competitive in the future.