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Throughout history, humanity has been captivated by extending the human lifespan. The search for a long and purposeful life continues to be an aspiration worldwide, and advances in science are increasingly supporting this aspiration.

The revelation of the Hayflick limit, which unveiled the finite lifespan of cells, shattered the belief in cell immortality, but also marked a turning point in our understanding of aging. The discovery opened new opportunities for investigating the biological mechanisms of growing old and exploring interventions that could achieve longevity in a healthy way.

At the heart of a long and healthy life is the idea of maintaining homeostasis, which is the body's ability to preserve a stable internal environment free from disease. Aging involves a complex interplay of biochemical and molecular pathways that can result in genetic instability and cellular senescence (cell death). As a result, there is a gradual decline in physiological function, contributing to age-related disorders such as cardiovascular diseases, cancer, neurodegenerative disorders, diabetes, osteoporosis, and vision loss. Revolutionary developments in the life science industry are making achieving a prolonged functional life possible.

DNA damage is a well-studied factor in aging. Within the nucleus of a cell, our genetic information is organised on coiled, double-stranded structures known as chromosomes. At the ends of these chromosomes, there are protective caps called telomeres which naturally shorten with age, leading to cellular and DNA damage. Telomere shortening is now being increasingly studied in relation to age-related conditions (1–5). Several factors, including environmental pollutants, toxins, radiation, and unhealthy lifestyle habits contribute to telomere shortening through oxidative stress. Conversely, some cancer cells have genetic abnormalities that allow them to restore and lengthen their telomeres. This enables them to continue to grow indefinitely, posing a threat to health.

Biotechnology offers the promise of targeting these complex genetic mechanisms without causing unintended consequence and addressing age-related cellular dysregulation. Gene editing using the Nobel prize-winning CRISPR-Cas9 technique, has the potential to precisely correct faulty genes. Scientists are also investigating molecular pathways like mTOR and AMPK signalling that regulate cellular functions such as protein synthesis, cell growth, and autophagy (cellular recycling and repair). Rapamycin – originally an anti-fungal agent - and metformin – used for type 2 Diabetes, have shown potential in addressing age-related cellular damage caused by dysregulation of these pathways.i

CRISPR-Cas9 system

CRISPR-Cas9 system diagram

Source: ‘Random mutagenesis in vegetatively propagated crops: opportunities, challenges and genome editing prospects’, Researchgate, June 2022

Recently there has been a rise in biotechnology startups focusing on longevity. A notable example is Altos Labs, which launched in 2022, founded on the groundbreaking discovery made by Shinya Yamanaka. His research revealed that specific factors can reprogramme adult cells into a flexible state called pluripotency, rejuvenating cells. Technological advancements such as artificial intelligence (AI) and personalised medicine also offer exciting possibilities. AI and machine learning can be used to analyse vast datasets to identify specific biomarkers of aging and predict potential health risks. Personalised medicine could customise interventions based on individual genetic predispositions.

Pluripotent shares – the process

Pluripotent shares – the process diagram

Source: Axial Discovery - Cell reprogramming, Joshua Elkington, 12 December 2022

A longer functional life is not all about new and exciting technologies. According to the World Health Organisation, 74% of deaths globally were from non-communicable diseases. These include heart attacks, stroke, chronic obstructive pulmonary disease, diabetes, and Alzheimer’s disease and other dementias. Preventing, diagnosing early, and effective treatment of these conditions will go a long way in extending functional lives. And so, in addition to new techniques, screening, diligence about one’s health, exercising, sleeping enough, and eating well still count for a lot when it comes to longevity. And one does not have to worry about the societal and ethical implications of tinkering with Mother Nature.

Whenever we think about altering the natural order of things, we must consider unintended consequences. Longevity has societal and ethical costs. Suppose we all live longer healthier lives, what impact does that have on finite natural resources that are already under pressure such as fresh water, arable land and clean air? What will be the impact on biodiversity? How much more can modern economies accommodate an expansion in populations (notwithstanding the impact of falling fertility rates) when it comes to the provision of amenities, local services such as refuse collection, or even building more homes? Will there be enough jobs for everyone? Will the retirement age have to drift higher?

Scientific advancements need to be made in log-step with a cultivation of universal ecological literacy and consider the ethical perspectiveii. Personalised medicine can be precise and very useful, but it is costly and so may be available for the rich only – would it be right that the haves can have longer healthier lives, while the have-nots die young?

Living longer and more productive lives is already within reach. Being diligent about one’s health to prevent, diagnose and treat disease early remains the single biggest intervention one can make to live longer. There are many scientific advancements that can then be used to be more precise and more effective in those endeavours.

Recently, a class of medicines called glucagon-like proteins (GLP-1s) used to treat diabetes and obesity, were shown to reduce the risk of death from heart attacks and stroke, while also protecting the kidneys and the liver and reducing cholesterol – this potentially addresses many of the top killers of todayiii. We expect science to keep advancing and the promise of longevity to come ever closer.


* The author would like to acknowledge the valuable assistance of colleague Yvie Lock, in compiling this article

 

References

1 López-Otín C, Kroemer G. Hallmarks of Health. Vol. 184, Cell. Cell Press; 2021. p. 33–63.

2 Suarez LM, Diaz-Del Cerro E, Felix J, Gonzalez-Sanchez M, Ceprian N, Guerra-Perez N, et al. Sex differences in neuroimmunoendocrine communication. Involvement on longevity. Mech Ageing Dev. 2023 Apr 1;211.

3 Izadi M, Sadri N, Abdi A, Zadeh MMR, jalaei D, Ghazimoradi MM, et al. Longevity and anti-aging effects of curcumin supplementation. GeroScience. Springer Science and Business Media Deutschland GmbH; 2024.

4 Thai NQN, LaCroix AZ, Haring B, Wactawski-Wende J, Manson JAE, Posis AIB, et al. The association of leukocyte telomere length with exceptional longevity among older women. Geroscience. 2024 Apr 1;46(2):2083–92.

5 Li Z, Zhang Z, Ren Y, Wang Y, Fang J, Yue H, et al. Aging and age‐related diseases: from mechanisms to therapeutic strategies. Vol. 22, Biogerontology. Springer Science and Business Media B.V.; 2021. p. 165–87.

i Rapamycin: one drug, many effects - PMC (nih.gov)
ii Ecology: An Ethical Perspective | Learn Science at Scitable (nature.com)
iii News Details (novonordisk.com)