Abstract
Anti-ageing research is moving at a fast pace and in multiple directions, but the single biggest change that has occurred in the last decade is a shift in its objective from lifespan to healthspan. Meaningless and painful extra few years are useless, but modest longevity with good health, free from disease and disability, is now the new goal. New research is bridging molecular biotechnology and aesthetic surgery platforms and the paradigm of anti-ageing medicine has pivoted from superficial aesthetics to targeted cellular rejuvenation, creating a crucial intersection with regenerative plastic surgery.
The breakthrough domains include epigenetic reprogramming, senolytics, metabolic modulation and artificial intelligence. The research on rapamycin, an immunosuppressant, metformin, an oral hypoglycaemic and Glucagon-like peptide-1 (GLP-1) drug for weight loss and nicotinamide adenine dinucleotide boosters to study their anti-ageing effect is progressing at different stages. Senolytics that kill the senescent cells or zombie cells of the ageing body are being studied in early human trials to ascertain their safety and efficacy. Cellular reprogramming by four Yamanaka factors is the newest avenue of research in geroscience, where ageing cells are reset partially just enough to wipe away the ‘epigenetic marks’ of ageing without erasing a cell’s identity.
Keywords
Introduction
There has never been a more exciting and a more confusing time to be reviewing anti-ageing research. Pharmacies are selling vitamins and antioxidants, wellness podcasts are promising everything except the moon, and glossy magazines are bombarding us with promises of pills, peptides and protocols that claim to roll back the clock. Billionaires are investing fortunes into longevity startups. Tech entrepreneurs such as Bryan Johnson are publicly tracking their ‘biological age’ down to the decimal point. In laboratories across the world, scientists are seriously talking about treating ageing itself as a disease that can be slowed or even partly reversed.
On the other hand, molecular anti-ageing interventions are morphing from hypothetical therapeutics into clinical reality, providing plastic surgeons with tools to enhance structural tissue longevity. Traditionally, facial ageing has been managed through macro-structural techniques, including autologous fat transfer, rhytidectomy and deep-plane lifting. While these interventions address volumetric deflations and structural ptosis, they fail to arrest the underlying microscopic and molecular processes of tissue degeneration. Over the past decade, anti-ageing research has fundamentally pivoted away from cosmetic modification and toward cellular rejuvenation.
A Shift in Thinking: From Lifespan to Healthspan
The first thing to understand is that the anti-ageing field has matured. A decade ago, the conversation was about ‘living to 150’. Today, serious researchers talk about something much more useful: Healthspan, the number of years you live in good health, free from disease and disability. It is not about adding days to your life anymore; it is about adding life to your days. The goal is not to add 10 miserable years to the end of life. It is to compress sickness into a much shorter window at the very end, so that you are vigorous and independent well into your eighties and nineties.
Scientists now believe ageing itself drives most of the chronic diseases we associate with getting older, such as heart disease, cancer, Alzheimer’s, diabetes and arthritis. If we can slow the underlying process even modestly, then we can delay all of those conditions at once. That insight is what is driving the modern field of ‘geroscience’, and it is why so many therapies, once dismissed as fringe, are now in serious clinical trials. The ageing of cutaneous layers, subcutaneous fat pads and musculoskeletal attachments is governed by conserved biological hallmarks: Genomic instability, telomere attrition, epigenetic alterations and chronic sterile inflammation (‘inflammaging’). Rather than operating purely as functional architects, future plastic surgeons will increasingly adopt the role of translational tissue engineers.
From the vast ocean of NES research in anti-ageing, we will discuss some repurposed metabolic therapeutics, nicotinamide adenine dinucleotide (NAD+) boosters, senolytice, epigenetic reprogramming, cellular reversal and artificial intelligence (AI) driven drug discovery and compound generation.
Repurposed Metabolic Therapeautics
Rapamycin
Rapamycin stands out as one of the most promising compounds in current anti-ageing research. Initially developed as an immunosuppressant for transplant patients, it has demonstrated impressive lifespan extension in mice, even when treatment begins later in life. It functions primarily by blocking the mTOR pathway, a key regulator of cell growth and nutrient sensing. 1 While the results in animal models are compelling, evidence in humans remains limited and inconclusive. A comprehensive 2025 review published in the journal Ageing noted that, despite widespread enthusiasm, there is still no robust clinical data confirming that low-dose rapamycin meaningfully slows human ageing or extends lifespan. 2 A few small-scale studies have reported potential benefits, such as reduced visceral fat and favourable changes in certain biological age indicators, 3 but these trials were generally brief, underpowered and not specifically designed to assess longevity outcomes. Possible side effects include increases in blood lipids, higher inflammation markers and reduced muscle gains from exercise. The largest human rapamycin trial to date is currently underway at the University of Arizona, with results anticipated in the next few years. 4 For now, it remains an exciting but unproven option, used off-label by some longevity specialists, yet not recommended for widespread use.
Metformin
Metformin, a widely used and well-tolerated diabetes medication for over six decades, has drawn interest from anti-aging researchers after observational data suggested that people taking it may experience lower rates of age-related diseases and have longer lifespans as compared to non-diabetics.5,6 The definitive test of its anti-ageing properties is the Targeting Ageing with Metformin trial, which aims to recruit over 3,000 older adults and monitor them over 6 years for delays in the onset or progression of chronic conditions such as cardiovascular disease, cancer and dementia. 7 Wake Forest University School of Medicine is coordinating this multicentric trial across 14 US cities. Although funding challenges have slowed progress, the trial could provide the high-quality evidence the field requires. Metformin is inexpensive, generic and generally safe, though it may cause gastrointestinal discomfort and could slightly reduce exercise-induced muscle gains. Some doctors already prescribe it off-label for delaying the development or progression of age-related chronic diseases, such as heart disease, cancer and dementia, but most experts recommend waiting for stronger trial results.
GLP-1 Drugs
Popular Glucagon-like peptide-1 (GLP-1) medications such as Ozempic, Wegovy and Mounjaro, primarily known for significant weight loss, are now being investigated for broader anti-ageing effects. By promoting weight reduction, lowering inflammation and easing metabolic strain, these drugs have been linked to decreased risks of heart disease, kidney problems and possibly cognitive decline. 8 The key debate is whether they directly influence the ageing process itself or simply mitigate the damaging effects of obesity. Regardless, they are expected to play an increasingly important role in future longevity strategies.
NAD+ Boosters
NAD+ boosters are supplements intended to elevate levels of NAD+, a vital coenzyme involved in cellular energy production, DNA repair and metabolic health. NAD+ concentrations naturally decline with age, so compounds such as nicotinamide mononucleotide and nicotinamide riboside (NR) aim to restore youthful levels and potentially rejuvenate cellular functions and vitality. 9 Research confirms that these NAD+ boosters effectively raise NAD+ in the bloodstream. 10 Some small clinical trials have observed modest benefits, including improvements in blood pressure, cholesterol profiles, arterial stiffness and sleep. However, other studies, particularly in healthy individuals, have shown minimal or no clear advantages. For example, a trial testing NR in long COVID patients found little impact on fatigue or cognitive symptoms. 11 At standard doses, NAD+ boosters appear safe, but their ability to meaningfully extend healthspan in non-deficient adults remains unproven. They are also relatively costly when taken at effective levels.
Senolytics
With ageing, certain cells cease dividing but evade normal cell death, becoming senescent. These ‘zombie cells’ 12 accumulate in tissues and secrete inflammatory factors that harm surrounding healthy cells, contributing significantly to chronic inflammation, frailty and age-related diseases. 13 Senolytics are a class of drugs developed to selectively eliminate these problematic cells. The best-known senolytic combination is dasatinib (a chemotherapy agent) paired with quercetin, a plant-derived flavonoid commonly referred to as D + Q. 14 Fisetin, another flavonoid abundant in strawberries, has also garnered attention. 15 Early human studies, though limited in size, have shown encouraging signs, such as better cognitive function and physical mobility in older individuals at risk for Alzheimer’s, 16 and accelerated wound healing in aged skin using a topical senolytic formulation. 17 That said, the field has encountered challenges, including the high-profile failure of UBX0101 in a Phase II osteoarthritis trial. 18 Optimal dosing, treatment frequency and patient selection are still being refined. Senolytics represent one of the most dynamic areas in geroscience, but more rigorous evidence is needed before their benefits can be considered established.
Epigenetic Reprogramming and Cellular Reversal
Cellular reprogramming is among the most ambitious and potentially transformative approaches in anti-ageing science. It builds on the Nobel Prize-winning work of Shinya Yamanaka, who discovered that adult cells can be reprogrammed into a stem-cell-like state using four specific genes, now known as Yamanaka factors (Oct4, Sox2, Klf4 and c-Myc). 19 The current goal is partial reprogramming, activating these factors just enough to reverse epigenetic signs of ageing while preserving the cell’s specialised identity. In mouse studies, this technique has yielded striking outcomes, including longer lifespans, restored vision, enhanced organ performance and partial reversal of ageing biomarkers. 20 Major companies such as Altos Labs (backed by Jeff Bezos) and Retro Biosciences (supported by Sam Altman) have raised substantial funding to pursue this technology. In January 2026, the FDA approved the first human trial of partial reprogramming by Life Biosciences. Their experimental therapy, ER-100, uses gene therapy delivered to the eye to address optic nerve damage in glaucoma and non-arteritic anterior ischaemic optic neuropathy patients. 21 This initial trial is deliberately narrow in scope, but success could pave the way for broader applications against multiple age-related conditions. While still in very early stages, this line of research is widely regarded as genuinely groundbreaking.
AI-driven Drug Discovery and Compound Generation
The traditional drug discovery pipeline has historically been slow, inefficient and cost-prohibitive. The integration of advanced deep learning architectures and neural networks has completely restructured this landscape. AI is now utilised to screen millions of molecular structures simultaneously, predicting binding affinities, pharmacokinetic profiles and cellular toxicities with high accuracy. 22 Machine learning algorithms achieved a 70% success rate in discovering and synthesising entirely novel life-extending compounds. AI models can bypass years of blind in vitro screening by simulating exactly how molecules interact with mammalian ageing pathways.
For clinical practitioners, this rapid acceleration shortens the timeframe required for novel topical formulations, post-laser recovery serums and scar-mitigating compounds to transition from laboratory benches to clinical practice.
What’s Mostly Hype?
Many expensive anti-ageing therapies have far less evidence than their marketing suggests. Stem cell injections at offshore clinics, ‘young blood’ plasma transfusions, full-body cryotherapy, IV vitamin drips, and most ‘anti-ageing peptides’ promoted online fall into this category. They range from probably useless to potentially risky to outright dangerous. The only thing common in them is that they are all expensive, lack peer-reviewed clinical trials and are not FDA approved. However, there is a marketing cacophony surrounding them.
Footnotes
Author’s Contribution
S. Bhattacharya: Concept, design, literature search, drafting and revision.
Declaration of Conflicting Interests
The author declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
Ethical Approval
Not applicable.
Funding
The author received no financial support for the research, authorship and/or publication of this article.
Patient Consent
Not applicable.