Top 10 Longevity & Anti-Aging Breakthroughs of 2025: What the Year Taught Us About Extending Human Healthspan

Introduction

We’re now halfway through the “Decade of Healthy Aging” (2021–2030). In the year 2025, what specifically stands out as the most impactful research findings and headlines from this calendar year? This review provides a breakdown of the top 10 longevity insights gained in 2025.

1. Two Decades of the NIA Interventions Testing Program: What Really Extends Lifespan? 

Key Findings

• Rapamycin remains the single most reliable lifespan extender across sexes.
• Lifespan-extending compounds consistently target metabolic resilience, stress response, and immune, or inflammation, regulation.
• Combination therapies may outperform single interventions.

Expanded Insight

The Interventions Testing Program (ITP), launched in 2004, is widely looked to as the gold standard in aging research because each intervention is tested across three independent sites with diverse mouse models. Over the past two decades, the ITP has tested 54 molecules for their lifespan extension benefits [1]. A review published in the Journal of Gerontology, synthesized two decades of work, revealing patterns that are now shaping the design and advancement of this important work into human trials [1]. According to ITP data, rapamycin’s reliability across sex, age of initiation, and dosage strategies reaffirmed its position as the most validated lifespan-extending compound in mammals. Rapamycin was associated with a roughly 15-20% increase in longevity in mice [1]. Other promising interventions include SGLT2i, which improved longevity by 13.6% in male mice [1].

One of the most impactful insights over the last two decades is that combination interventions may amplify benefits. Specifically, rapamycin plus acarbose produced better benefits than either in isolation, up to a 36.6% increase in median lifespan [1]. This finding strengthens the emerging view that aging is best targeted using multi-pathway intervention(s). The ITP review will likely guide longevity drug development for the next decade, as continued research will test specific interventions and combinations in females and males to uncover sex-specific benefits.

2. The PEARL Trial: Low Dose Weekly Rapamycin, Safe + Lean Mass Benefits in Women

Key Findings

• Lean tissue mass and self-reported pain improved significantly for women using 10 mg rapamycin.
• Self-reported emotional well-being and general health also improved for those using 5 mg rapamycin.
• Low-dose, intermittent rapamycin administration over 48 weeks is relatively safe in healthy, normative-aging adults, and was associated with significant improvements in lean tissue mass and pain in women.

Expanded Insight

The PEARL trial was a 48-week, double-blind, randomized, placebo-controlled clinical study examining the safety and healthspan effects of intermittent low-dose, once weekly, rapamycin in healthy, normative-aging adults aged approximately 50–85 years [2]. Over the course of one year, participants received weekly doses of either placebo, 5 mg, or 10 mg of compounded rapamycin. The primary outcome, visceral adiposity, did not differ significantly between groups. In women taking the higher 10 mg dose, there was an increase in lean mass, a 6% change  (p = 0.018) from baseline at 48 weeks [2]. There were also self-reported improvements in pain, emotional well-being, and general health [2].

Importantly, safety data showed no increase in serious adverse events compared with placebo, supporting a favorable safety profile for intermittent low-dose rapamycin [2]. These outcomes suggest that rapamycin may support aspects of functional aging and subjective health, pointing to rapamycin’s promise as a geroprotective intervention that could preserve muscle mass and improve quality of life in aging adults. The PEARL trial has become a landmark for translating rapamycin, one of the strongest geroprotective compounds in animals, into human aging outcomes. Continued work in this area, focusing on additional lab biomarkers and generic rapamycin, which has higher bioavailability, will further inform healthspan extension protocols. 

3. Daily Low-Dose Daily Rapamycin Shows Promising Cardiovascular Benefits 

Key Findings

• Low Dose 1mg/day rapamycin is safe and produces cardiovascular benefits in 8 weeks.
• Endothelial function and reduced arterial stiffness were improved.
• Lower systemic inflammatory biomarkers after sustained low-dose use.

Expanded Insight

For years, rapamycin was associated primarily with immunosuppression in transplant recipients, making many clinicians cautious about preventative or longevity applications. A 2025 pilot clinical study published in GeroScience investigated whether short-term inhibition of the mechanistic target of rapamycin (mTOR) with low-dose rapamycin could improve, a key marker of healthy aging, cardiovascular, and endothelial function in older men [3].

This was a very small, proof-of-concept trial, in which six healthy male participants aged 70–76 took 1 mg of rapamycin daily for 8 weeks. Detailed cardiac MRI assessments revealed statistically significant improvements in diastolic heart function, including enhanced transmitral blood flow (p = 0.033), peak filling rates (p = 0.014), and blood acceleration (p = 0.004) [3]. Additionally, rapamycin treatment significantly increased microvascular endothelial function, measured by improved nitric oxide–mediated vasodilation responses, suggesting better vascular health. Low-dose daily rapamycin was well-tolerated with no adverse events directly related to the drug, underscoring and supporting existing safety data. 

The cardiovascular improvements from this small trial appeared within months, much sooner than would be expected if the effects were driven primarily by metabolic health improvements alone. These findings provide preliminary human evidence that short-term mTOR inhibition by rapamycin can bolster aspects of cardiovascular performance and vascular function in older adults, aligning with animal data on rapamycin’s geroprotective effects and highlighting potential for larger, controlled trials to test its role in delaying cardiovascular aging and improving healthspan once long-term safety is established. 

4. Are GLP-1 Drugs the First True Longevity Medications?

Key Findings

• GLP-1s reduce all-cause mortality in multiple analyses.
• Strong effects on inflammation, metabolic flexibility, and cardiovascular outcomes.
• Researchers now propose GLP-1s as first-in-class longevity therapeutics.

Expanded Insight

GLP-1 drugs have been around for decades, and they have already transformed obesity and diabetes care. However, this year, 2025, evidence appears to have reached a critical mass in favor of longevity benefits far beyond weight loss. Reduced inflammation, improved endothelial function, and normalized metabolic signaling position GLP-1s as multi-system rejuvenators [4].

A publication in Nature Biotechnology from November of 2025 argues that the broad benefits of GLP-1s are the closest thing to what the longevity-focused field has long sought in a gerotherapeutic: one intervention, multiple organs improved, healthspan improved, and mortality risk reduced [4]. 

No gerotherapeutics have yet been approved by the FDA. Compared with previous anti-aging candidates, GLP-1s are much more effective as metabolic drugs, and there are vastly more human data for them. They clearly target many of the hallmarks of aging, including damage at the genetic, epigenetic, protein, mitochondrial, cellular, extracellular, and systemic levels [4]. Paired with complementary lifestyle habits and personalized nutrition, GLP-1s are positioned as an excellent first-line longevity drug, and they may be the first true longevity drug approved if this momentum continues.

5. GLP-1 and Cancer Risk: Major Clinical Update

Key Findings

• No increased total cancer risk across large patient datasets and meta-analyses.
• Early evidence suggests a reduced risk of obesity-related cancers.
• GLP-1s may lower cancer-promoting inflammation and growth signaling.

Expanded Insight

For years, safety critics questioned whether GLP-1 agonists might increase cancer risk, especially pancreatic or thyroid cancers. In 2025, a large review published in the Journal of Clinical Investigation brought more data to provide clarity around the topic of cancer. The investigation focused specifically on evaluating GLP-1s and cancer risk, including thyroid, pancreatic, gastrointestinal, and hormone-dependent malignancies [5]. The findings were that there is no meaningful increase in overall cancer incidence, and potential protective effects for certain cancers associated with GLP-1s [5]. Interestingly, the distribution of incretin receptors on specific tumor types, there are likely more advantages associated with dual agonist GLP-1 medications, which will have a direct impact on a wider range of tumor cells than single agonist GLP-1s [5].

Because chronic inflammation and insulin resistance fuel tumor growth, GLP-1 drugs may exert anti-cancer effects through metabolic normalization. This reinforces their emerging role as agents that provide broad-spectrum metabolic health protection. Looking to the future, there are several ongoing clinical trials for GLP-1 receptor therapies in cancer patients, as well as some preclinical studies, that will help shape clinical perspectives on the timing, duration of GLP-1 receptor agonist treatment, and concurrent use with established anticancer therapies [5]. The year 2025 was a turning point in cancer-related research for GLP-1s as data continues to support gerotherapeutic benefits that extend to cancer protection.

6. SGLT2 Inhibitors May Lengthen Telomeres

Key Findings

• A human study showed telomere length increased in patients taking SGLT2 inhibitors.
• Reduced oxidative stress and improved mitochondrial biomarkers.
• Potential first FDA-approved drug class with telomere-preserving effects.

Expanded Insight

Telomere shortening is one of the most widely recognized indicators of biological aging. While exercise, diet, and stress reduction can modestly affect telomere length, no FDA-approved medication had convincingly lengthened telomeres until this 2025 report. This year, a research publication from Cell Reports Medicine included data in which a 6-month sodium-glucose co-transporter 2 (SGLT2) inhibitor intervention produced robust telomere length increases rather than merely slowing its age-associated shortening [6]. This is a highly unusual (and exciting) finding in human aging research. 

Telomeres, the protective DNA caps at chromosome ends, typically shorten with each cell division and are widely considered a hallmark of aging; shorter telomeres are linked to age-related diseases and mortality across large cohorts [6]. This research, in which a SGLT2i inhibitor intervention, henagliflozin (10 mg/day) for 26 weeks, led to measurable telomere elongation [6]. The findings of this research challenge the prevailing notion that telomere dynamics in adults are unidirectional, only shortening over time, and suggest that under certain conditions, cellular aging markers can be reversed or improved.

The demonstration of increased telomere length in this clinical or translational study introduces a compelling proof-of-concept that human cellular aging may be more malleable than previously thought, opening the door for future therapies aimed at enhancing cellular repair and reducing age-related disease risk. If validated in additional cohorts, SGLT2 inhibitors may become one of the most important metabolic longevity tools available today, bridging cardiometabolic improvements, cognitive function, and direct anti-aging effects on telomeres. In conclusion, the authors of this research call for future research to consider head-to-head trials of SGLT2i or GLP-1s to determine which one has better anti-aging effects and even explore the potential synergistic effects of their combined use in anti-aging treatment [6].

7. SGLT2 Inhibitors Inhibit Cellular Senescence

Key Findings

• Reduced senescent cell burden in multiple tissues.
• Decreased SASP inflammatory cytokines.
• Improved regenerative and metabolic capacity.

Expanded Insight

A 2025 review highlights an unexpected and promising new direction in aging research: repurposing sodium-glucose co-transporter 2 (SGLT2) inhibitors as senotherapeutics that target the biology of cellular aging [7]. Cellular senescence, the irreversible arrest of cell division accompanied by a pro-inflammatory senescence-associated secretory phenotype (SASP), accumulates with age and drives many chronic diseases. 

Beyond their glucose-lowering effects, SGLT2 inhibitors have been linked in experimental models to reduced markers of senescence, improved endothelial and cardiovascular function, enhanced mitochondrial health, and activation of longevity-linked pathways like AMPK and SIRT1, suggesting they could attenuate or even reverse aspects of tissue aging [7]. Unlike most interventions that merely slow age-related decline, mounting evidence suggests SGLT2 inhibitors can modulate hallmarks of aging such as inflammation, oxidative stress, telomere length, and cellular senescence itself [7].

This year, 2025, saw enhanced research and clinical focus on repositioning common metabolic drugs for anti-aging benefits. By linking established cardiovascular and renal protective effects to mechanisms of aging biology, this work provides a compelling framework for future clinical trials aimed at extending healthy lifespan and preventing age-associated pathologies beyond diabetes. Most senolytics remain experimental, but the finding that SGLT2 inhibitors reduce senescence markers in humans represents a monumental development, suggesting the benefits of SGLT2 inhibitors extend far beyond disease etiologies linked with glucose control to mechanistic targets of aging.

8. FDA Removes the Black Box Warning From Hormone Replacement Therapy for Women

Key Findings

• Removal of the FDA black box warning for HRT
• HRT benefits include a higher quality of life, symptom relief, improved bone density, cardiometabolic improvements, and reduced all-cause mortality.

Expanded Insight

In November 2025, the U.S. Food & Drug Administration (FDA), in coordination with the Department of Health and Human Services, announced it is initiating the removal of longstanding “black box” warnings from menopausal hormone replacement therapy (HRT). This decision follows a comprehensive review of current scientific evidence, including reanalyses showing that for women who begin HRT within about 10 years of menopause onset, the benefits such as relief from debilitating hot flashes, night sweats, and genitourinary symptoms outweigh potential risks, and may be associated with reduced all-cause mortality, lower fracture risk, and improvements in cardiovascular and cognitive outcomes [8]. 

The removal of these warnings represents a major course correction of decades-old messaging that contributed to widespread HRT hesitancy. After the 2002 Women’s Health Initiative study led to alarm and sharp declines in HRT use, many millions of women avoided, or were denied therapies that could have markedly improved quality of life and long-term health, often due to fear rooted in misinterpreted or outdated data. By aligning regulatory language with current evidence and encouraging open, evidence-based patient-provider discussions, this policy shift is poised to restore confidence in HRT, expand access for appropriate candidates, and acknowledge the real lived experiences of women whose health and well-being were impacted by the fear inspired by those earlier warnings. 

The updated stance validates what many menopause researchers have long argued: personalized, modern HRT is safe for most women and may offer long-term protective health benefits. This regulatory shift may become one of the most impactful women’s health milestones of the decade.

9. Testosterone Replacement Therapy

Key Findings

• Physiological testosterone replacement supports healthspan by preserving muscle mass, bone density, and metabolic health, and physical resilience
• Testosterone plays an important, often under-recognized, role in women’s health as well, with evidence suggesting benefits for libido, mood, bone health, and cognitive function 

Emerging 2025 research on testosterone replacement therapy (TRT) underscores its potential to improve key aspects of healthspan, the period of life spent in good health, particularly in people with clinically confirmed low testosterone. In aging men and women, physiological declines in testosterone are closely tied to reductions in muscle mass, bone density, metabolic health, and libido, all of which contribute to frailty and reduced quality of life with age [9]. Randomized controlled trials and systematic reviews show that TRT can boost lean muscle mass, improve bone mineral density, enhance sexual function, and ameliorate anemia and insulin sensitivity when testosterone is restored to optimal physiological levels [9]. 

These effects address multiple hallmarks of aging, such as sarcopenia, metabolic dysfunction, and physical decline, suggesting that, for appropriately selected individuals, TRT may extend functional health and vitality. Recent safety data, including from cardiovascular outcome studies, particularly the 2023 TRAVERSE trial, provide reassurance that TRT can be administered without a significant increase in cardiovascular events when appropriately monitored [9]. 

While most clinical evidence to date focuses on biologically confirmed hypogonadism in men, there is growing interest in sex hormone optimization in women as well. Testosterone plays important roles in female libido, mood, bone health, and cognitive function, and studies have shown that testosterone administration can improve aspects of verbal memory and well-being in postmenopausal women. As of 2025, research suggests that maintaining hormone balance through TRT may contribute not just to symptom relief but to broad healthspan and longevity improvements, particularly when combined with lifestyle interventions such as resistance training and metabolic health optimization.

10. Urolithin A Cardioprotection & Mitochondrial Quality
 

Key Findings

• UA supplementation reduced plasma ceramides, predictors of cardiovascular disease
• UA’s ability to improve mitochondrial quality underscores its promise as a longevity-focused intervention beyond heart health alone because mitochondrial function is a requisite for healthy cells throughout the body.

Expanded Insight

A 2025 study published in iScience revealed that urolithin A (UA), a gut microbiome-derived postbiotic, supports cardiovascular health by enhancing mitochondrial quality and function. The heart is arguably the highest energy-demand organ in the body; therefore, enhancing mitochondrial function has pronounced benefits in the heart. In preclinical models of natural aging and heart failure, UA supplementation activated mitophagy, the selective removal of damaged mitochondria, which in turn improved both systolic and diastolic cardiac function and restored ultrastructural integrity in ageing heart muscle cells [10]. 

In healthy older adults, 1000mg/day UA supplementation for 4 months significantly lowered plasma ceramides, lipid biomarkers strongly associated with cardiovascular risk. These data suggest UA supplementation may reduce age-related heart disease risk through improved mitochondrial quality control. The findings of this 2025 research position UA as a promising nutritional approach to preserve cardiac function and support healthy aging by targeting mitochondrial function, a core hallmark of aging.

Looking Ahead to 2026 and Beyond

According to the United Nations (UN) World Population Prospects 2024, the number of individuals aged ≥65 years is anticipated to double from 761 million in 2021 to 1.6 billion in the next 2-3 decades [11]. As governments, biotech companies, and academic centers ramp up investment in geroscience, the field risks splintering into parallel but non-complementary research. 

As 2026 approaches, the longevity field is shifting toward fewer, preclinical, proof-of-concept experiments to focused clinical evaluations where there is a need for clinical standardization worthy of a new biomedical science discipline. 

There are several exciting ongoing human trials that illustrate a shift toward a human longevity focus. In particular, listed at clinicaltrials.gov, there are fascinating human longevity trials that will further inform this field in the coming years: 

• Everolimus Aging Study (EVERLAST) (NCT05835999)
• The Role of Sirolimus in Preventing Functional Decline in Older Adults (NCT05237687)
• Effect of Rapamycin in Ovarian Aging (NCT05836025)
• Tirzepatide to Slow Biological Aging (NCT07220473)
• Aging Well: Targeting Obesity With GLP-1 Agonists to Enhance Physical and Vascular Health in Postmenopausal Women (NCT07057310)
• Evaluation of Urolithin A and Fisetin on Sleep and Aging Biomarkers (NCT06990256)

Conclusion

One of the biggest takeaways from 2025 is that aging is not driven by a single biological mechanism. The year’s research underscores that targeting multiple hallmarks of inflammation, metabolism, senescence, mitochondrial function, and nutrient signaling leads to better outcomes than focusing narrowly on one pathway or mechanistic target.

This shifts longevity science closer to a familiar model seen in oncology, infectious disease, and cardiology, where combination therapy and adjuvants are embraced for better outcomes. More clinical trials leveraging both lifestyle and appropriate polypharmacy combinations (e.g., GLP-1s + SGLT2 inhibitors, HRT + rapalogs) are expected. As we head into 2026, longevity science has clearly emphasized clinical trial designs, which makes translational leaps from animal models less significant and accelerates longevity progress. The field of anti-aging biology and geroscience is full of promise as we look ahead at human aging as a malleable biological process.