What are the key interventions in longevity medicine?

Key Interventions in Longevity Medicine

The most effective interventions in longevity medicine include calorie restriction, exercise, mTOR inhibitors (like rapamycin), and dietary modifications that reduce activation of nutrient-sensing pathways, as these directly target fundamental aging mechanisms and improve morbidity, mortality, and quality of life outcomes. 1

Dietary Interventions

• Calorie restriction is one of the most well-established longevity interventions, reducing frailty in naturally aging mice, genetically manipulated mice, and nonhuman primates 1
• Protein restriction (particularly limiting specific amino acids like methionine) reduces mTOR activation and extends lifespan in rodent models 1
• Mediterranean-style diets high in fruits, vegetables, fish, whole grains, legumes/pulses, and low in red meat and sugar-rich foods are consistently associated with longevity and better cardiometabolic outcomes 2
• Intermittent fasting reduces frailty markers, though effects appear to be more pronounced in males than females 1
• Ketogenic diets that mimic aspects of calorie restriction have shown modest effects on frailty indices in aging mice 1

Pharmaceutical Interventions

• mTOR inhibitors (e.g., rapamycin) extend healthspan and reduce frailty indices in multiple animal models, targeting a key nutrient-sensing pathway involved in aging 1
• Metformin, an antidiabetic drug, is currently undergoing clinical trials for its potential longevity effects by improving metabolic parameters and reducing inflammation 3
• Acarbose, another antidiabetic medication, is being investigated for longevity effects in clinical trials 3
• Senolytics (drugs that target senescent cells) are emerging as promising interventions, with human clinical trials underway 1

Lifestyle Interventions

• Regular exercise, particularly aerobic exercise and high-intensity interval training, consistently reduces frailty in animal models 1
• Voluntary wheel running improves physical performance and reverses frailty phenotypes in aging mice 1
• Sleep regulation and stress reduction techniques contribute to improved psycho-biological resilience and may slow aging processes 4
• Meditation and specific breathing techniques can help regulate stress responses that contribute to accelerated aging 4

Supplements and Nutraceuticals

• Antioxidants like resveratrol reduce frailty in naturally aging mice 1
• Alpha-ketoglutarate supplements attenuate frailty in aging mice, suggesting potential for repurposing as anti-aging interventions 1
• Allicin (derived from garlic) inhibits inflammation and reduces frailty markers in aging mice 1
• Vitamin D supplementation is being investigated in large clinical trials for its efficacy in reducing all-cause mortality 3

Combination Approaches

• Drug treatment plus exercise regimens may better attenuate or even reverse frailty accumulation in aging than single interventions 1
• De-prescribing unnecessary medications can be a viable strategy to combat frailty in older adults, as polypharmacy increases frailty scores in animal models 1

Monitoring and Assessment

• Frailty indices provide a translational measure of health in aging and can be used to monitor intervention effectiveness 1
• Biological age markers (DNA methylation clocks, telomere length) can help assess the impact of interventions on aging processes 1

Pitfalls and Caveats

• Many longevity interventions show sex-specific effects, with some treatments being more effective in males than females or vice versa 1
• Extrapolating from animal models to humans must be done cautiously, as humans have different lifespans and physiological responses 1
• Combination of multiple interventions is likely necessary for meaningful impacts on human longevity, as addressing only one disease of aging (e.g., cardiovascular disease) would only add approximately 2.87 years to average lifespan 1
• Timing of interventions is critical, with some showing greater benefits when started earlier in life while others can be effective even when initiated in later life 1

Longevity medicine represents a shift from treating individual diseases to addressing the fundamental processes of aging, with the goal of extending healthy lifespan rather than merely extending life with disease and disability 1.