Q4 2025 State of the Science: Longevity Medicine
The longevity field continues rapid evolution with expanding research, increasing clinical applications, and growing commercialization. This quarterly update synthesizes the most meaningful developments with an evidence-based clinical perspective.
Major Developments This Quarter
1. GLP-1 Receptor Agonists Beyond Diabetes
Evidence continues to mount that GLP-1 receptor agonists exert effects beyond glucose control, including cardiovascular protection independent of weight loss, early signals of neuroprotection, possible reductions in addictive behaviors, and systemic anti-inflammatory effects.
Current Assessment: These drugs are likely to become important longevity tools. However, questions remain regarding long-term use, optimal dosing strategies, muscle mass preservation during rapid weight loss, and cardiovascular safety in specific populations. Enthusiasm is justified but must be tempered by incomplete long-term data.
2. Epigenetic Age Clocks Advancing
Second- and third-generation epigenetic clocks are showing improved prediction of healthspan, better correlation with functional outcomes, and the ability to identify specific biological systems aging more rapidly.
Clinical Application: These tools are beginning to move from research into clinical practice. They are useful for identifying accelerated biological aging, tracking response to interventions, and motivating behavior change — but should complement, not replace, functional assessments.
3. Senolytic Therapy Progress
Multiple senolytic compounds are now in human trials. Preliminary data suggests potential benefits in specific conditions such as osteoarthritis, pulmonary fibrosis, and frailty. Broad anti-aging applications remain unproven, and safety concerns persist with some agents.
My Position: Still too early for use in healthy individuals. Possible role in specific age-related diseases under supervision. Natural compounds such as fisetin or quercetin alone have weaker evidence but better safety profiles.
4. Exercise as Medicine: Evidence Strengthens
Exercise — particularly resistance training — continues to demonstrate unmatched longevity benefits. New data shows even small amounts of high-intensity exercise produce disproportionate mortality reduction.
- Resistance training reduces all-cause mortality by 20–30%
- Exercise may reduce dementia risk more than any pharmaceutical
- Midlife muscle mass strongly predicts late-life function
Key Message: Exercise should no longer be treated as optional in longevity protocols. It is the foundation on which all other interventions should be built.
5. Metformin Data Maturing
While the TAME trial continues enrollment, observational data keeps accumulating. Recent meta-analyses suggest modest benefits in non-diabetics, though effect sizes are smaller than initially hoped. Some evidence suggests interference with exercise adaptations.
Current Recommendation: Reasonable for those with insulin resistance or prediabetes. Benefits less clear for metabolically healthy individuals. Not a replacement for lifestyle intervention.
What’s Overhyped
- NAD+ Precursors: Blood level increases without consistent functional benefit
- Young Blood / Plasma: Minimal human evidence, heavy marketing
- Peptides: Limited efficacy data, unknown long-term safety
- Hyperbaric Oxygen: Narrow indications, broad anti-aging claims premature
What’s Underappreciated
- Sleep Quality: Fragmentation predicts cognitive decline and metabolic dysfunction
- Protein Intake: Most older adults consume far below optimal levels
- Social Connection: Loneliness predicts mortality comparable to smoking
- Dental Health: Periodontal disease linked to inflammation and cardiovascular risk
Looking Ahead to 2026
- Expanded GLP-1 data beyond obesity and diabetes
- First major results from longevity trials including TAME
- Greater use of multi-omic and wearable data
- Broader clinical adoption of epigenetic age tracking
My Priorities for Patients
- Resistance training 2–3× weekly minimum
- Protein intake 1.2–1.6 g/kg/day
- Sleep optimization as top priority
- Metabolic health and inflammation reduction
- Stress management and social connection
- Selective use of proven interventions
BOTTOM LINE
Longevity science is advancing rapidly, but the foundations remain unchanged. Exercise, nutrition, sleep, and stress management deliver the highest return on investment. Advanced interventions should augment — not replace — these fundamentals.