Longevity Science: Decoding the Biology of Ageing

19 Jul 2024

10 Min Read

Associate Professor Dr Yau Weng Keong (Academic Contributor), Dr Mugilarasi Arasarethinam (Academic Contributor), The Taylor's Team (Editor)

IN THIS ARTICLE

In recent years, the field of longevity science has garnered significant attention, capturing the imagination of scientists and the public alike. This burgeoning discipline seeks to unravel the molecular mechanisms that underpin ageing and age-related diseases, with the ambitious goal of extending not just lifespan but healthspan – the period of life spent in good health.

The quest to understand and influence the biological processes of ageing is not a new one; it has fascinated humanity for centuries. From ancient civilisations searching for the elixir of life to modern scientific advancements, the desire to prolong youth and vitality has been a constant. Today, we stand on the brink of a new era, where tangible anti-ageing interventions are within reach.

The History of Longevity Science

The pursuit of longevity is as old as civilisation itself. Ancient cultures were replete with myths and legends about the elixir of life, a magical potion that could grant eternal youth. The quest for immortality is prominently featured in the epic tales of Gilgamesh and the alchemical traditions of ancient China and Egypt.

For instance, the first Emperor of China, Qin Shi Huang, famously sought out an elixir of immortality, consulting alchemists and ingesting various concoctions in his quest for eternal life. These early efforts, although based on myth and mysticism, underscore humanity’s enduring desire to transcend the limits of natural lifespan.

In ancient Greece, the physician Hippocrates emphasised the importance of a balanced lifestyle in maintaining health and longevity. Similarly, Ayurvedic practitioners in India advocated for a holistic approach to health, integrating diet, exercise, and meditation to prolong life.

Scientific Milestones

The transition from myth to science began in earnest in the 19th and 20th centuries. One of the pioneers in the study of ageing was Elie Metchnikoff, a Russian zoologist who coined the term ‘gerontology’ in the early 1900s. Metchnikoff’s research on phagocytosis and his belief in the beneficial effects of certain bacteria on gut health were groundbreaking. He proposed that ageing was due to the accumulation of harmful bacteria in the gut and advocated for the consumption of probiotics to promote longevity.

Gerontology (noun)

Gerontology is the study of ageing and the challenges that come with it. This field looks at the biological, psychological, and social aspects of growing older. Gerontologists work to understand how ageing affects individuals and society, aiming to improve the quality of life for older adults. They explore ways to help people age healthily, maintain their independence, and stay active in their communities.

The 20th century saw significant advancements with the discovery of the double helix structure of deoxyribonucleic acid (DNA) by Watson and Crick in 1953, which revolutionised our understanding of genetics and ageing. Leonard Hayflick’s work in the 1960s revealed that human cells have a limited capacity to divide, known as the Hayflick limit, challenging previous assumptions about cellular immortality and highlighting the intrinsic limits to cell lifespan.

The latter part of the 20th century and the early 21st century have been marked by an explosion of research into the molecular mechanisms of ageing. The discovery of telomeres and the enzyme telomerase by Elizabeth Blackburn and her colleagues in the 1980s provided critical insights into the ageing process at the cellular level.

Associate Professor Dr Yau Weng Keong

Longevity science, like senolytics and caloric restriction, is mainly in early animal studies and may not translate to humans. Some stem cell studies are in phase III trials. High costs may limit access, but we must continue pursuing these advancements for future health benefits.

Associate Professor Dr Yau Weng Keong

School of Medicine

Understanding the Biology of Ageing

At the core of ageing lies a complex interplay of molecular and cellular processes. One of the key mechanisms is cellular senescence, where cells lose their ability to divide and function effectively. Senescent cells accumulate over time, contributing to tissue dysfunction and age-related diseases. This process is often triggered by DNA damage, which increases with age due to factors like oxidative stress, environmental toxins, and natural cellular processes.

Telomeres, the protective caps at the ends of chromosomes, play a crucial role in cellular ageing. Each time a cell divides, its telomeres shorten slightly. Eventually, they become too short to protect the chromosomes, leading to cell death or senescence. The enzyme telomerase can extend the length of telomeres, but its activity diminishes with age in most human cells, except in certain cell types like stem cells and cancer cells.

Cancer cells vis - 3d rendered image, enhanced scanning electron micrograph (SEM) of cancer cell.

Oxidative stress, caused by the accumulation of reactive oxygen species (ROS), is another significant factor in ageing. ROS are by-products of normal cellular metabolism, but in excess, they can damage cellular components such as DNA, proteins, and lipids. The body’s antioxidant systems usually neutralise ROS, but their efficiency declines with age, leading to increased cellular damage.

Genetic and Epigenetic Factors

Longevity is also influenced by genetic factors. Research has identified several genes associated with increased lifespan. For instance, the SIRT1 gene, part of the sirtuin family, is involved in cellular stress responses and has been linked to longevity in various organisms. Sirtuins play a role in DNA repair, metabolic regulation, and reducing oxidative stress.

FOXO3 is another gene that has been linked to longevity. It is involved in regulating the expression of genes that combat oxidative stress and inflammation, promoting cell survival and repair mechanisms. Variants of the FOXO3 gene are associated with increased lifespan in humans and other species.

Asian Senior Adult couple holding glasses of milk together at home

Epigenetics, the study of changes in gene expression without altering the underlying DNA sequence, is also crucial in understanding ageing. Epigenetic modifications, such as DNA methylation and histone modification, can regulate gene activity in response to environmental and lifestyle factors. These modifications accumulate over a lifetime and can influence the ageing process by altering the expression of longevity-associated genes.

Current Anti-Ageing Interventions

Senolytics

One of the most promising areas of anti-ageing research involves senolytics, a class of drugs designed to target and eliminate senescent cells. These cells, which have stopped dividing but do not die off, accumulate with age and contribute to chronic inflammation and tissue dysfunction. By selectively removing senescent cells, senolytics can alleviate the detrimental effects they cause, potentially reversing or slowing the ageing process. Studies in animal models have shown that senolytics can improve physical function, enhance cardiovascular health, and extend lifespan. Early human trials are showing encouraging results, suggesting that these drugs could become a cornerstone of future anti-ageing therapies.

Closeup of a tablet on the hands of an old woman

Caloric Restriction and Mimetics

Caloric restriction (CR), the practice of reducing calorie intake without malnutrition, has been consistently shown to extend lifespan and improve healthspan in various species, from yeast to primates. CR works by triggering a metabolic shift that enhances stress resistance, reduces oxidative damage, and improves cellular maintenance processes. However, long-term caloric restriction can be challenging to maintain for humans.

To address this, researchers are developing caloric restriction mimetics – compounds that mimic the beneficial effects of CR without requiring a significant reduction in food intake. One well-known CR mimetic is resveratrol, a compound found in red wine, which activates similar cellular pathways as caloric restriction. Another promising compound is rapamycin, an immunosuppressant that has been shown to extend lifespan in mice by inhibiting the mTOR pathway, a key regulator of cell growth and metabolism.

Regenerative Therapies

Regenerative therapies aim to restore function to damaged tissues and organs, thereby promoting healthy ageing. Stem cell therapy is at the forefront of this field, leveraging the unique ability of stem cells to differentiate into various cell types and repair or replace damaged cells. For instance, mesenchymal stem cells (MSCs) have shown potential in regenerating bone, cartilage, and muscle tissue. Clinical trials are exploring the use of MSCs for treating age-related conditions such as osteoarthritis and cardiovascular diseases.

Tissue engineering and organ regeneration are also making significant strides. Advances in 3D printing technology have enabled the creation of bioengineered tissues and organs that can potentially be used for transplantation. Researchers are working on developing functional organs, such as hearts, kidneys, and livers, which could one day replace failing organs in elderly patients, significantly extending their healthspan and improving their quality of life.

Inside view of human internal vein or artery

The Quest to Reverse Ageing

Bryan Johnson, a tech entrepreneur and founder of Kernel, is renowned for his ambitious quest for longevity. He has invested millions into anti-ageing research and developed a comprehensive health regimen called ‘Blueprint’.

This meticulous protocol aims to reverse ageing and achieve biological youth, striving to maintain the physical condition of an 18-year-old. Johnson's routine includes consuming over 100 supplements daily, adhering to a strict diet, undergoing various medical treatments, and constant health monitoring by more than 30 doctors. His ultimate goal is to make death optional, challenging the limits of the human lifespan.

His motivation extends beyond personal health; it also involves his family. Notably, he has used his 17-year-old son's blood plasma in his pursuit of youth. This controversial practice, known as parabiosis, involves the transfusion of young blood to potentially rejuvenate the body and reverse ageing processes.

Johnson's pursuit raises ethical concerns, particularly regarding accessibility and equity. The treatments and regimen he follows are extraordinarily expensive, making them accessible only to the wealthy. This disparity underscores the need for equitable access to ensure the benefits of longevity science are available to all, irrespective of socioeconomic status.

Furthermore, the potential for significantly extended lifespans presents challenges related to resource allocation and sustainability. Longer, healthier lives could strain resources such as healthcare, housing, and food supplies. Therefore, policymakers and scientists must collaborate to develop sustainable solutions that balance population growth with resource availability, ensuring that extended lifespans do not exacerbate resource scarcity.

Emerging Areas of Research in Longevity Science

Several emerging areas of research hold great potential for extending healthspan and lifespan. One such area is the study of the microbiome – the community of microorganisms living in our bodies. Recent research suggests that the microbiome plays a significant role in ageing and age-related diseases. By understanding how the microbiome influences health and ageing, scientists can develop probiotics and other interventions to promote a healthy microbiome and improve overall healthspan.

Another promising area is the study of proteostasis, the balance of protein production, folding, and degradation within cells. Disruptions in proteostasis are linked to ageing and various age-related diseases. Researchers are exploring ways to enhance proteostasis through small molecules and other interventions, potentially mitigating the effects of ageing at the cellular level.

The Asian adult daughter is helping her mother repot a house plant at home.

Dr. Mugilarasi Arasarethinam

Advancements in longevity science, particularly gerontological interventions, can reduce healthcare strain by delaying late-life morbidity. However, we must be wary of the cost and accessibility challenges of advanced treatments. Additionally, slowing biological aging alone is insufficient. We must also address social determinants of health such as education, employment, and housing.

Dr. Mugilarasi Arasarethinam

School of Medicine

Conclusion

As we move forward, the future of longevity science looks bright, with emerging research areas and personalised medicine poised to transform our understanding and management of ageing. By integrating scientific advancements with public health initiatives and ethical frameworks, we can work towards a future where extended lifespans enhance the quality of life for all individuals. In the words of Dr Elizabeth Blackburn, Nobel Laureate, ‘The key to a long life is not just the years in our life, but the life in our years,’ capturing the essence of our quest to add life to years, ensuring a vibrant, fulfilling existence for people worldwide.

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