Can we age without becoming ill?
Scott Broadbent is a 70-year-old retired pharmaceutical chemist who is participating in a clinical trial at the Buck Institute for Research on Aging, in California. The trial's purpose is to assess the safety of a ketone ester supplement in a drink Broadbent consumes every morning to see if it could slow the ageing process.
Geroscience and Aging Research:
Geroscience is the research behind ageing and chronic age-related illnesses.
Geroscientists are currently researching potential medicines to prolong the ageing process and avert diseases that reduce the quality of life at an older age.
“Let’s build a medicine that would be safe enough for someone in midlife to take almost like a supplement, like a daily vitamin, but with much more profound biological effects,” says James Peyer, CEO of Cambrian Bio in New York City.
The Challenges with an Aging Population:
Experts predict that by 2030 there will be around 1 billion people aged 65 or older.
Source: World Population Prospects 2022, United Nations
The current issues within the healthcare system are the lack of nursing homes and personal care staff - “We don’t have the nursing homes. We don’t have the personal care staff to deal with this at all.” says Laura Niedernhofer, a geneticist and researcher at the University of Minnesota, Minneapolis. Therefore, having access to drugs that could help older generations stay healthy would be highly beneficial to society. However, the development of such drugs is an expensive and laborious process.
Geroscience Experiments:
A molecular biologist at University of California, Cynthia Kenyon, carried out a significant experiment in which she discovered that a mutation in the roundworm C. elegans could double its lifespan.
This posed the question to many scientists: if the process of ageing is adaptable and if it is possible to develop solutions to the root of ageing rather than the accumulation of diseases.
Potential Drug Therapies:
Currently, there are no therapies for humans, however some compounds that can delay the ageing process have been discovered in mice, fruit flies and worms.
Rapamycin is a compound found in a soil sample in 1964 from Easter Island. This drug is often given to patients who have undergone organ transplants to prevent the immune system from rejecting the organs. Additionally, Rapamycin extends the duration of the lives of yeast, flies and mice. It works by inhibiting a protein complex called mTOR (mechanistic target of rapamycin) which has a role in protein synthesis and cell growth.
Another group of potential drug therapies are senolytics. They target senescent cells that are no longer dividing but are not dead. The cells release chemical signals that can cause inflammation, interrupt tissue repair and even cause neighbouring cells to become senescent. Senolytics have shown promise with mice and are currently being tested within humans.
Scientists have recognised 12 hallmarks of ageing that have the potential to expand the average lifespan. These hallmarks are interconnected by the products produced from interactions between genes. It is these products that drugs such as rapamycin and senolytics target.
Genomic instability includes changes to DNA, chromosomal rearrangements and defects in nuclear architecture.
Telomere attrition is the cumulative damage or loss of DNA at the ends of chromosomes, called telomeres.
Epigenetic alterations can change how a gene is expressed without changing the DNA itself, such as methylation.
Loss of proteostasis refers to imbalances in proteins in the body, which can lead to the formation of protein aggregates, as in Alzheimer’s.
Disabled macroautophagy leaves cells unable to sequester and digest material in the cytoplasm, thus affecting the replacement of organelles.
Dysbiosis is the disruption of the body’s microbial communities, which play a role in nutrient digestion, disease protection and more.
Chronic inflammation increases with ageing, both across the body and locally, and typically comes with a decline in immune function.
Altered intercellular communication brings more noise into the system, disrupting neural, neuroendocrine and hormonal signalling.
Stem cell exhaustion leads to a reduction in tissue renewal rates across the body and can limit tissue repair after injury.
Cellular senescence, when cells stop dividing but don’t die, has been linked to kidney disease, diabetes, Alzheimer’s, Parkinson’s and more.
Mitochondrial dysfunction can prevent a cell from producing the energy it needs, as well as contribute to inflammation and cell death.
Deregulated nutrient-sensing affects a whole series of pathways that shape cell activity, which makes diet a practical ageing intervention.
ICONS & SOURCE: C. LÓPEZ-OTÍN ET AL/CELL 2023
Preventions for advancements:
A major challenge in geroscience is trying to prove that there is a compound that could help the ageing process in humans. It is also an expensive and lengthy process. Geroscientists also must battle against societal views of ageing such as, “There’s nothing you can do to stop ageing” Another argument is that if the average life span can increase, the population will also increase, but we are already facing overpopulation.
Another large obstacle is hype. In the present day, people are interested in running away from ageing and so some companies place extortionate prices on their products such as vitamins or moisturisers which claim to make one appear more youthful. However, most of these products do not have proven benefits.
In conclusion, there is a potential future for geroscience as there are therapies that have worked on other organisms and clinical trials are constantly ongoing to adapt and implement these therapies for humans. However, the organisms that these therapies are effective for, do not share similarities with humans so there is a lot of uncertainty surrounding if these drugs would help improve the lives of elder humans.
Maebella Patel
References:
https://www.sciencenews.org/article/aging-geroscience-health-span-drugs [accessed 30/01/2024]
https://population.un.org/wpp/ [accessed 30/01/24]
https://pubmed.ncbi.nlm.nih.gov/8247153/ [accessed 30/01/24]
https://www.sciencenews.org/archive/long-lived-worm-hints-genetics-aging [accessed 31/01/24]
https://www.sciencenews.org/article/healthy-old-age-may-trump-immortality [accessed 31/01/24]