The Science of Turning Back the Clock
For the first time in human history, we have the tools to target the fundamental mechanisms of ageing itself, potentially extending healthspan and improving quality of life in our later years.
Explore the ScienceFor thousands of years, ageing has been viewed as an inevitable, one-way journey of decline. But what if we could change that trajectory? What if the wrinkles, fading memory, and physical frailty we associate with getting older weren't mandatory, but manageable? This isn't science fiction—it's the promising frontier where bioengineering meets geroscience, a field dedicated to understanding and modifying the fundamental processes of ageing.
Today, for the first time in human history, the global population of older adults is growing rapidly. By 2050, there will be more than 2.1 billion people aged 60 and over, representing over 21% of humanity 7 . This demographic shift represents one of the most significant social transformations of our century, presenting both a remarkable achievement and an enormous challenge. While we've succeeded in extending lifespans, we now face the critical task of improving healthspan—the period of life spent in good health, free from chronic disease and disability 4 .
Enter bioengineering—the application of engineering principles to biological systems. Through innovative technologies, computational models, and cutting-edge molecular interventions, scientists are developing tools to not just treat age-related diseases, but to target the underlying mechanisms of ageing itself.
Suggest ageing follows a biological timetable, much like the genetic program that guides childhood development.
The truth likely involves elements from both perspectives. As one researcher notes, "These theories may interact with each other in a complex way" 1 . Modern bioengineers are learning to manipulate both programmed pathways and repair accumulated damage.
In 2013, scientists identified nine hallmarks of ageing, creating a framework that has guided research and intervention development. These hallmarks represent fundamental cellular and molecular processes whose dysfunction drives ageing 9 . A tenth hallmark—compromised autophagy—has since been added, recognizing the importance of the cellular recycling system in maintaining youthfulness 9 .
| Hallmark | Description | Potential Bioengineering Interventions |
|---|---|---|
| Genomic Instability | Accumulation of damage to nuclear and mitochondrial DNA | Gene editing technologies (CRISPR), DNA repair enzymes |
| Telomere Attrition | Shortening of protective chromosome ends | Telomerase activation, telomere extension therapies |
| Epigenetic Alterations | Changes in gene expression without DNA sequence changes | Epigenetic reprogramming, chromatin remodeling |
| Loss of Proteostasis | Decline in protein folding and degradation | Proteostasis regulators, enhanced autophagy inducers |
| Deregulated Nutrient Sensing | Dysfunction in metabolic signaling pathways (e.g., mTOR, insulin/IGF-1) | Rapamycin analogs, caloric restriction mimetics |
| Mitochondrial Dysfunction | Decline in energy production and increased oxidative stress | Mitochondrial antioxidants, mitophagy enhancers |
| Cellular Senescence | Accumulation of non-dividing, inflammatory cells | Senolytics (drugs that clear senescent cells) |
| Stem Cell Exhaustion | Decline in regenerative capacity | Stem cell therapies, regenerative medicine approaches |
| Altered Intercellular Communication | Changes in signaling between cells (e.g., chronic inflammation) | Anti-inflammatory therapies, cytokine modulation |
| Compromised Autophagy | Decline in cellular waste removal and recycling | Autophagy enhancers, mTOR inhibitors |
Bioengineers have developed sophisticated algorithms to quantify biological ageing using biomarkers from blood tests and other clinical data.
The BioAge R package implements three methods to calculate biological age: Klemera-Doubal biological age (KDM), PhenoAge, and homeostatic dysregulation 2 8 .
Cellular senescence refers to cells that have stopped dividing but refuse to die, accumulating in tissues and secreting inflammatory molecules.
Bioengineers are developing senolytics—therapies that specifically target and eliminate senescent cells 9 .
While many dramatic interventions are being tested in laboratories, one of the most influential human trials demonstrating that ageing can be modified involved a surprisingly simple (though challenging) intervention: caloric restriction. The CALERIE™ (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy) randomized controlled trial represents a landmark in ageing research—the first-ever human trial of long-term calorie restriction in healthy, non-obese adults 8 .
The CALERIE trial, conducted across three research centers in the United States, was meticulously designed to assess the effects of sustained caloric restriction on human biology:
218 healthy, non-obese men and women aged 21-50 years with BMIs between 22.0 and 27.9 kg/m².
Participants randomly assigned to either a calorie restriction group (25% reduction) or control group (regular diet).
Two-year intervention with extensive monitoring to ensure adherence.
Blood chemistry, metabolic rate, body composition, insulin sensitivity, and biological age assessments using multiple algorithms 8 .
The findings from the CALERIE trial provided compelling evidence that ageing is indeed modifiable in humans:
| Parameter | Change in Calorie Restriction Group | Significance |
|---|---|---|
| Pace of Ageing (KDM Biological Age) | Slowed compared to control group | Participants' biology was "younger" than expected |
| Metabolic Health | Improved insulin sensitivity, reduced cholesterol | Reduced risk factors for age-related diseases |
| Oxidative Stress | Reduced markers of oxidative damage | Less cumulative molecular damage |
| Inflammation | Decreased inflammatory markers | Reduced chronic inflammation |
Perhaps most remarkably, the analysis using biological age algorithms revealed that the caloric restriction intervention had actually slowed the participants' rate of biological ageing 8 . Their bodies were physiologically younger than would be expected for their chronological age, suggesting that the intervention was affecting fundamental ageing processes, not just disease risk factors.
The mTOR pathway is a key nutrient sensor that promotes growth when nutrients are abundant. Restricting calories tones down this pathway 4 .
Sirtuins are proteins that regulate cellular health and are dependent on NAD+, a molecule whose levels increase during fasting 4 .
Calorie restriction boosts cellular cleanup processes, removing damaged components and proteins 9 .
Bioengineers working on ageing have a sophisticated arsenal of tools at their disposal. Here are some of the key reagents and technologies driving the field:
| Tool/Reagent | Function | Application in Ageing Research |
|---|---|---|
| Senolytics (e.g., dasatinib, quercetin, fisetin) | Selectively induce death of senescent cells | Clearing "zombie cells" from tissues to reduce inflammation and improve function |
| NAD+ Boosters (e.g., NMN, NR) | Increase levels of nicotinamide adenine dinucleotide (NAD+) | Activating sirtuins to improve cellular repair and metabolic function |
| Rapamycin | Inhibitor of mTOR pathway | Mimicking aspects of caloric restriction to extend healthspan |
| CRISPR-Cas9 Gene Editing | Precisely modify DNA sequences | Correcting age-related mutations, studying gene function in ageing |
| Telomerase Activators (e.g., TAT2) | Maintain or extend telomere length | Preserving cell division capacity and reducing cellular senescence |
| Biological Age Algorithms (e.g., KDM BA, PhenoAge) | Quantify biological age from biomarker data | Assessing effectiveness of interventions without long-term mortality studies |
| Single-Cell RNA Sequencing | Profile gene expression in individual cells | Mapping age-related changes in rare cell populations like stem cells |
| Organ-on-a-Chip Systems | Microengineered models of human organs | Testing age-related tissue dysfunction and interventions in human models |
The field of bioengineering for healthy ageing is advancing at an astonishing pace, with several promising directions emerging:
AI is analyzing massive datasets to identify new drug candidates and personalize anti-ageing regimens. Companies like Insilico Medicine have used AI to identify novel senolytics in record time 6 .
The World Health Organization has declared 2021-2030 the "Decade of Healthy Ageing," focusing on maintaining functional ability in older age 7 .
The future of healthy ageing research lies in bridging traditionally separate fields—bringing together AI experts with biologists, clinicians with engineers, and policymakers with researchers 6 .
As the population ages, the goal is no longer simply extending lifespan, but rather expanding healthspan—ensuring that added years are characterized by vitality, purpose, and independence. Through the innovative application of bioengineering, we are steadily moving toward a future where growing older doesn't mean fading away, but rather continuing to thrive.