The question of ageing, and if we can slow down the process down, is an age old one. The past decade has witnessed a remarkable surge in scientific advancements across various disciplines. The cost of human genome sequencing has plummeted from a staggering $1 billion in 2003 to well under $1,000 by 2022. This accessibility is evident in companies like 23andMe offering personalised DNA profiling for just a few hundred dollars. CRISPR, or clustered regularly interspaced short palindromic repeats, has emerged as a revolutionary tool for directly manipulating genes. It allows for precise editing, akin to modifying text, with the potential for inheritance if applied to egg and sperm cells. This groundbreaking technology has already yielded success stories in treating sickle cell disease and beta-thalassemia, and holds immense promise for tackling cystic fibrosis and cancer. Further fueling optimism, researchers at the University of Amsterdam recently achieved a significant milestone: eliminating HIV from infected cells in a lab setting using CRISPR, paving the way for a potential cure.
In addition to transforming agriculture, improving the environment and preventing disease, CRISPR also has the potential to rejuvenate cells. As we age compounds, such as proteins, can stick to DNA, turn genes on and off and modify their functions. These marks are known as the epigenome. Scientists are finding ways to remove these, restoring the DNA to its original state. Epigenetic marks are just one of the many biological mechanisms by which we age. The progressive loss of the body’s ability to repair itself, leads to widespread cellular damage. Proteins and cellular detritus start to clog up organs and tissues. Chromosomes start to unravel and genetic mutations accumulate. Some cells become cancerous and immune defences weaken. Mitochondria, the powerhouses of our cells, fall into disrepair and the ends of our chromosomes, known as telomeres, start to wear down.
Another hallmark of ageing is cellular senescence. This is when cells have suffered some sort of irreversible damage and entered a state called senescence where they are beyond repair and stop dividing. They are the undead of cells, known as zombies. They pump out inflammatory chemicals that signal other cells to eat them up, removing them and their inflammation from the body. This process is called autophagy. As we age our bodies’ abilities to clear away zombie cells decreases meaning they hang around creating chronic low-level inflammation, so analogous with ageing, scientists have named it “inflammaging”. Senolytic compounds are chemicals that will remove these zombie cells, lowering inflammaging and therefore reducing chronic illnesses associated with old age, such as cancer, atherosclerosis, type 2 diabetes, osteoarthritis, Parkinson’s, Alzheimer’s and cataracts.
Many studies have shown that taking senescent cells from an old mouse and transplanting them into a young one, ages it prematurely and it acquires the diseases of old age. The opposite is also true. If you remove senescent cells from old mice, their condition improves!
Scientists are working on drugs that can clear out zombie cells. These senolytic drugs have already entered human trials! Dasatinib, a leukemia treatment, and a plant pigment, quercetin, used in combination, have shown very promising results.
Another approach is senomodifiers, which don’t kill senescent cells, but encourage them to start dividing again. The most promising of these are based on resveratrol, a natural compound found in grape skin.
Metformin is an FDA-approved drug used successfully to treat diabetes for more than 60 years. Studies have already shown that metformin can delay ageing in animals. It may also influence fundamental ageing factors that underlie multiple age-related conditions in humans. The Targeting Aging with Metformin (TAME) Trial will test whether those taking metformin experience delayed development or progression of age-related chronic diseases—such as heart disease, cancer, and dementia.
Currently several supplements are available that purport to slow the ageing process. There are some promising results and a lot of potential, however it is early days and more human research is needed. There is always a risk when buying such supplements as they are not regulated and there is no way of knowing if you can get exactly what is advertised on the label.
In 2019, Google claimed a landmark achievement in computing: “quantum supremacy.” Their machine, harnessing the bizarre laws of the quantum world, could solve calculations in seconds that would take traditional computers millennia. Since then advances in computing, artificial intelligence (AI) have skyrocketed. In 2023, the University of Edinburgh developed an innovative method that employs artificial intelligence (AI) to identify senolytic drugs. By leveraging data from over 2,500 chemical structures extracted from past studies, the team successfully trained a machine-learning model to recognise the essential characteristics associated with chemicals possessing senolytic activity.
Experiments conducted in human cells within the laboratory setting, unveiled the remarkable capability of three chemicals, namely ginkgetin, periplocin, and oleandrin, to eliminate senescent cells while preserving the integrity of healthy cells.
There are currently nine hallmarks of ageing, knowledge of which is advancing at a rapid pace. AI will no doubt speed this up further, meaning that various ‘cures’ to ageing could become a reality in the not too distant future. Unfortunately, this isn’t likely to take the form of a single pill that will restore the youth and vigour of your 20s. It is more likely we’ll see medications that work on specific aspects of ageing, reducing the risk of age-related diseases and offering several extra years of good health, with the added bonus of a longer lifespan. Life expectancy in the UK is going up. Unfortunately, the number of years of good health is not increasing at the same rate. In the UK people are currently spending an average of 12 years in ill-health. This is 14% longer than 30 years ago.
This opens up many ethical and practical questions. Governments around the world are already consulting with scientists on what this means for society. Some might say an ageing population is a burden. However, on the flip side, more people actively contributing to the economy is a positive. Another common argument is that the population is already too large. Population models from the Institute for Health Metrics and Evaluation suggest a global peak around mid-century, followed by a decline to roughly current levels by 2100. Indeed, many serious demographers are worrying about underpopulation. The debates surrounding population ethics are numerous. Andrew Steel, author of Ageless: The New Science of Getting Older Without Getting Old, articulates this perfectly. On his website he offers a free chapter on the ethics of a world without ageing. We live in exciting times and science is advancing faster than ever. Let’s hope it is used wisely and kindly for the benefit of all mankind.
