Longevity Knowledge BETA

Lifespan Extension Interventions

Table of Contents

What are lifespan extension interventions?

Lifespan extension interventions are evidence-based approaches targeting the biological mechanisms of aging to extend both lifespan (total years lived) and healthspan (years in good health). Rather than treating individual diseases, these strategies address the root causes of aging itself. Research has identified conserved aging mechanisms across species including cellular senescence, genomic instability, epigenetic changes, and mitochondrial dysfunction [1]. While complete aging reversal remains theoretical, several interventions show measurable effects on aging biomarkers and age-related disease risk.

Dietary and metabolic interventions

Caloric restriction and various fasting protocols have demonstrated lifespan extension across multiple organism models [2]. In humans, these approaches improve metabolic markers including insulin sensitivity, inflammation levels, and cardiovascular risk factors. Time-restricted eating and periodic fasting may trigger cellular repair processes like autophagy—the body's mechanism for clearing damaged cellular components.

Metformin, a diabetes medication, shows associations with reduced all-cause mortality in observational studies. The ongoing TAME (Targeting Aging with Metformin) trial aims to establish whether metformin can delay age-related diseases in non-diabetic individuals [3].

Pharmacological approaches

Rapamycin and its analogs (rapalogs) inhibit the mTOR pathway, a central regulator of cell growth and metabolism. Studies in mice demonstrate lifespan extension even when treatment begins in later life [4]. Human trials are evaluating safety and efficacy for age-related conditions.

Senolytics represent a newer class of compounds designed to selectively eliminate senescent cells—"zombie cells" that accumulate with age and secrete inflammatory factors. Early clinical trials show promising results for age-related diseases including osteoarthritis and idiopathic pulmonary fibrosis [5].

Lifestyle foundations

Exercise remains the most robust intervention for extending healthspan. Both aerobic and resistance training demonstrably reduce mortality risk, preserve cognitive function, and maintain muscle mass [6]. Combined with adequate sleep, stress management, and social connection, these lifestyle factors form the foundation of any longevity strategy.

Nutritional approaches including adequate protein intake, polyphenol-rich foods, and omega-3 fatty acids support cellular health. NAD+ precursors like nicotinamide riboside are being studied for their potential to restore cellular energy metabolism, though human evidence remains preliminary.

1.

Try time-restricted eating

Eating within an 8-10 hour window allows insulin levels to drop between meals, which helps restore sensitivity over time. Most of the benefit comes from extending the overnight fast — stop eating 2-3 hours before bed.
2.

Combine aerobic and resistance training

Aim for at least 150 minutes of moderate aerobic exercise per week plus two resistance sessions. The combination of both exercise types produces the greatest reduction in cardiovascular mortality risk.
pubmed.ncbi.nlm.nih.gov
3.

Stay informed about senolytics

Senolytic therapies that clear aged cells are advancing through clinical trials. While not yet widely available, understanding these developments helps you make informed decisions as they mature.
4.

Monitor metabolic markers regularly

Track fasting glucose, HbA1c, and lipid panels annually. These markers predict longevity better than weight alone and help identify intervention opportunities early.
5.

Prioritize sleep quality

Sleep deprivation reduces insulin sensitivity and increases cortisol. Aim for 7-9 hours of quality sleep to maintain healthy blood sugar regulation.
1.

What is the difference between lifespan and healthspan?

Lifespan is simply how many years you live. Healthspan is how many of those years you spend in good health, physically active, cognitively sharp, and free of chronic disease. Modern aging research focuses primarily on extending healthspan, because adding years of disability isn't the goal. The gap between lifespan and healthspan averages about 9 years in developed countries, and closing that gap is what most geroscience interventions aim to do.
2.

Are anti-aging supplements like NMN or resveratrol effective?

Evidence for NAD+ precursors (NMN, NR) and resveratrol in humans remains preliminary. While animal studies show promise, human trials have yielded mixed results. These supplements are generally safe but expensive, and their longevity benefits are unproven. Focus on established interventions like exercise and diet first.
3.

Is rapamycin safe for healthy people to take?

Rapamycin is FDA-approved for specific conditions but not for longevity in healthy individuals. It has significant side effects including immune suppression and metabolic disruption. Several clinical trials are currently evaluating lower, intermittent dosing protocols for safety and efficacy in aging. Do not use without medical supervision.
4.

What are senolytics and how do they work?

Senolytics are compounds that selectively destroy senescent cells, which are damaged cells that have stopped dividing but remain metabolically active, releasing inflammatory molecules. By inhibiting the pro-survival pathways that keep these zombie cells alive — particularly BCL-2 family proteins and tyrosine kinases — senolytics trigger apoptosis in senescent cells while leaving healthy cells unharmed.

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This content was created and reviewed by the New Zapiens Editorial Team in accordance with our editorial guidelines.
Last updated: February 26, 2026

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