The Science of longevity and healthy ageing

By Ananyaa Vishwanath 

Edited by Medha Vemuri

Introduction: 

The 21st century is witnessing one of the most profound demographic shifts in human history: a rapidly ageing population, fueled by longer life expectancy and declining fertility rates. This trend represents a major milestone for public health while simultaneously introducing substantial challenges for health systems around the world. Healthy aging, as defined by the World Health Organization, is the process of developing and maintaining the functional ability that enables wellbeing in older age [1] . The modern science of longevity aims not simply to extend lifespan (the number of years we live) but healthspan- the number of years lived in good health, free from chronic disease and functional decline. 

Today researchers are uncovering the biological mechanisms behind ageing, identifying interventions that slow these processes and exploring how lifestyle, environment and technology can reshape the ageing process. 

What is ageing and what are the biological hallmarks? 

Ageing is not a single process but an array of interconnected changes. The most widely accepted framework is the “hallmarks of ageing,” a set of nine foundational mechanisms identified in 2013 [2] and expanded in subsequent research. These include: 

 1) Genomic instability is the increased tendency of a cell’s DNA to accumulate mutations and structural damage. It results from accumulated DNA damage due to the environment - known as exogenous damage (e.g. radiation and toxins) and metabolic stress- known as endogenous processes (e.g. replication errors) leading to mutations that impair cell function or trigger cell death. 

 2) Telomere attrition is when the cells limits cellular replication as chromosome ends shorten, promoting reducing tissue renewal and causes cells to undergo apoptosis (the process of programmed cell death, where a cell triggers its own destruction)

 3) Epigenetic alterations disrupt normal gene expression patterns, causing cells to lose their identity and function. They do not modify the genetic sequence itself but instead influence how the code is interpreted. Over time, this regulatory drift gradually compromises cellular and tissue function. 

4) Loss of proteostasis leads to the accumulation of misfolded or damaged proteins, impairing cellular machinery and promoting toxicity and causes Alzheimer’s and Parkinson’s disease due to its inability to make and remove proteins efficiently. 

5) Deregulated nutrient sensing, particularly involving insulin, mTOR, and AMPK pathways, disrupts metabolic balance and accelerates ageing-related damage since it means that cells can no longer detect or respond to nutrient levels in the body. 

6) Mitochondrial dysfunction reduces energy production and increases reactive oxygen species, harming cells and tissues due to the mitochondria in the cells stop respiring effectively. 

7) Cellular senescence means that a cell is alive but stops dividing which causes damaged cells to stop dividing while secreting inflammatory factors that degrade tissue structure and function. 

8) Stem cell exhaustion is when stem cells lose their ability to divide, diminish and repair tissues meaning damaged or lost cells are not efficiently replaced, leading to tissue thinning, delayed healing, weakened immune responses and reduced organ function. 

9) Altered intercellular communication means that the cells no longer respond to signals properly hence promoting chronic inflammation and impaired signaling between cells, further driving tissue dysfunction and systemic ageing. 

Why is ageing a prevalent problem in the UK and the rest of the world? 

In the UK and worldwide, population ageing [3] intensifies existing social, economic and healthcare challenges as rising life expectancy and declining birth rates increase the proportion of older adults. Older populations have higher rates of chronic diseases such as cardiovascular disease, dementia and osteoporosis. This increases demand for long-term medical care and support while shrinking the working-age population that funds these services through taxation. This demographic imbalance strains public finances, reduces economic productivity and places growing pressure on families and communities to provide care, making population ageing a critical public health and societal issue. 

Breakthroughs in longevity research: 

LinkGevity [4]:

This company (established by 2 sisters- Dr Carina Kern and  Serena Kern-Libera)  has focused its research on a new AI-enabled drug discovery which hopes to target the root causes of aging (necrosis- death of most cells in a tissue) rather than just its symptoms, LinkGevity is creating a pioneering Anti-Necrotic therapeutic designed to transform the treatment of chronic and age-related diseases. Necrosis occurs when cells die in an uncontrolled manner which triggers inflammation and tissue damage, which can lead to chronic diseases such as Alzheimer's, cardiovascular disease and cancer. By focusing on targeting necrosis, the company aims to develop therapies that prevent or reverse the harmful effects of this form of cell death hence promoting healthier aging. The hope to begin the late stage clinical efficacy trials early next year particularly focused on the kidney, due to its easy identifiable decline in function as ageing occurs. 

It is being designed as a first-in-class treatment, meaning it’s one of the first to directly target necrosis as a mechanism of disease which could offer a transformative approach to treating chronic and age-related conditions.

Gene Editing (CRISPR) [5]: 

Gene editing, particularly using CRISPR-Cas9 technology, offers potential for slowing the aging process and increasing healthspan by directly modifying the genetic factors that drive age-related decline. Aging is influenced by the accumulation of genetic mutations and the gradual degradation of cellular functions over time. CRISPR allows scientists to edit or repair genes at precise locations in the DNA potentially reversing some of the damage caused by aging. By editing genes to maintain or restore telomere length, CRISPR could extend the lifespan of cells which delays aging as it improves tissue regeneration. Additionally, CRISPR can be used to repair genetic mutations that contribute to age-related diseases, such as Alzheimer's or muscular dystrophy (genetic disorders that cause progressive weakness and loss of muscle mass), by correcting the faulty genes responsible. 

In essence, gene editing with CRISPR has the potential to restore cellular health and repair age-related damage at the DNA level, which could ultimately slow aging and extend the period of life spent in good health thus increasing healthspan.

Ethical and social considerations of slowing the ageing process and longevity research: 

Longevity research aimed at slowing ageing raises clear ethical and social concerns, particularly regarding equity of access and long-term consequences for society. 

Ethically, if effective anti-ageing treatments are costly or limited they could deepen health inequalities by allowing wealthier individuals to live longer and healthier lives while others do not. There are also concerns about safety and informed consent, as intervening in fundamental biological processes may carry unknown long-term risks for the individual. 

Socially, widespread life extension could strain pension systems and healthcare services while also disrupting employment patterns by extending working lives and intensifying competition between generations. 

Together these issues highlight the need to balance scientific progress with fairness, sustainability and social responsibility.

What can you do right now to slow the ageing process? 

Calorie restriction (CR) [6]: 

Research was carried out by NIH (National Institute of Health) to assess whether CR was beneficial to human health. More than 200 healthy, middle aged volunteers were randomly allocated into two groups as part of the Comprehensive Assessment of Long-term Effect of Reducing Intake of Energy (CALERIE) scheme funded by the NIH . One was challenged to reduce their calorie intake by 25% for two years (average calorie intake is 2,000 kJ, so a 25% reduction is 500 kJ fewer, which is equivalent to that of 2 bagels). The results showed that on average the participants were able to reduce their calorie intake by 12.5% and lost approximately 10% of their body weight, mostly from fat. Studies of CALERIE participants showed that calorie restriction (CR) slowed biological ageing, with those in the CR group showing a reduced pace of ageing based on blood biomarkers. Although CR led to a slight reduction in muscle mass, muscle strength was maintained suggesting improved muscle quality. Further analysis of muscle biopsies revealed changes in the expression and splicing of over 1,000 genes, with increased activity in pathways linked to muscle repair, ageing and decreased inflammation. These findings suggest that CR may help preserve muscle function and overall health during ageing, though more research is needed.

Regular exercise: 

Research states that higher levels of physical activity increases the probability of healthy ageing by 39% [7]. This reference to a combination of moderate to vigorous exercise, including aerobic activity (e.g. brisk walking, jogging which improves cardiovascular health), muscle- stretching activities (e.g. lifting weights- helps maintain muscle mass and bone strength) and flexibility & balance exercises (e.g. yoga- reduce fall risk). Together these activities contribute to improved physical function.

Avoid smoking and consuming alcohol:

Smoking and alcohol consumption accelerate ageing by directly increasing biological ageing (captures how a person is aging, according to many different factors and biomarkers [8] ) at the cellular, tissue, and systemic levels. 

Smoking exposes the body to toxic chemicals that cause genomic instability and oxidative stress (condition that occurs when there is an imbalance between the production of reactive oxygen species and the body’s ability to neutralise them with antioxidants), leading to faster telomere shortening and increased cellular senescence. This results in chronic inflammation, impaired blood vessel function and reduced oxygen delivery to tissues, which accelerates the development of cardiovascular disease, respiratory decline, cancers and neurodegeneration. Smoking also disrupts normal repair mechanisms meaning damaged cells accumulate more rapidly, a key feature of accelerated biological ageing.

Harmful alcohol consumption further speeds up ageing by damaging organs such as the liver and brain, while increasing oxidative stress and inflammation throughout the body. Alcohol interferes with mitochondrial function and nutrient metabolism, reducing cellular energy production and impairing tissue maintenance. As people age reduced alcohol tolerance makes these effects more pronounced, even at lower levels of intake. 

Conclusion: 

Ageing is a complex biological process shaped by molecular damage, lifestyle choices and wider social factors but it is increasingly clear that the rate at which we age is not fixed. Advances in longevity research, from targeting fundamental mechanisms such as necrosis to gene editing technologies like CRISPR, offer promising opportunities to extend healthspan and reduce the burden of age-related disease. However, these innovations must be approached responsibly, with careful consideration of ethical, social and economic impacts. Importantly evidence shows that individuals can already influence their biological ageing through achievable lifestyle changes, including regular physical activity, calorie moderation and avoiding smoking & excessive alcohol consumption. Together, scientific progress and informed personal choices have the potential to support healthier ageing populations and improve quality of life in later years.

References :

1. “Healthy Ageing and Functional Ability,” October 1, 2025, https://www.who.int/news-room/questions-and-answers/item/healthy-ageing-and-functional-ability.

2. Carlos López-Otín et al., “The Hallmarks of Aging,” Cell 153, no. 6 (June 1, 2013): 1194–1217, https://doi.org/10.1016/j.cell.2013.05.039.

3. Age Uk, “State of Health and Care of Older People in England 2024,” Age UK, n.d., https://www.ageuk.org.uk/discover/2024/september/state-of-health-and-care-of-older-people-in-england-2024/.

4. Isabel Ely PhD, “Could the Future of Longevity Lie in Tackling Necrosis?,” Drug Discovery from Technology Networks (blog),May 12, 2025, https://www.technologynetworks.com/drug-discovery/blog/could-the-future-of-longevity-lie-in-tackling-necrosis-399511.

5. Prillaman, McKenzie. 2024. “Stanford Explainer: CRISPR, Gene Editing, and Beyond.” News.stanford.edu. Stanford Report. June 10, 2024. https://news.stanford.edu/stories/2024/06/stanford-explainer-crispr-gene-editing-and-beyond.

6. “Can We Slow Aging?,” National Institutes of Health (NIH), September 18, 2025, https://www.nih.gov/news-events/nih-research-matters/can-we-slow-aging.

7. Daskalopoulou, Christina, Brendon Stubbs, Christina Kralj, Artemis Koukounari, Martin Prince, and Matthew Prina. “Physical Activity and Healthy Ageing: A Systematic Review and Meta‑Analysis of Longitudinal Cohort Studies.” Ageing Research Reviews 38 (2017) 

8. “Understanding the Difference between Biological Age and Chronological Age - Mayo Clinic Press.” 2024. Mayo Clinic Press. July 25, 2024. https://mcpress.mayoclinic.org/healthy-aging/understanding-the-difference-between-biological-age-and-chronological-age/.

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