Here is the shortlist of the XPRIZE $100 Million Healthspan “Top 10” finalists (from the Milestone 2 Awardee Lookbook, Appendix F, attached below), with each team’s approach and its stated mechanism of action.
AgelessRx (Ann Arbor, MI) — A telehealth-delivered combination “longevity medicine” protocol. It stacks rapamycin, low-dose naltrexone, metformin, NAD+, glutathione, sermorelin, and tirzepatide with resistance training and health coaching. Mechanism: hits several aging pathways at once — mTOR inhibition, AMPK activation, NAD+ repletion, oxidative-stress reduction, and growth-hormone-axis signaling — plus a proprietary “Infinite Supplement” blend (alpha-ketoglutarate, quercetin, glucosamine, carnosine, pterostilbene, astaxanthin, curcumin).
Goda Lab (University of Tokyo / NanoTitan / Tohoku University / Tokyo Relife Clinic, Japan) — Engineered extracellular vesicles (EVs) from stem cells or plasma. Its “super homotypic targeting” (SHT) platform reprograms EV surfaces for precise tissue delivery. Mechanism: strengthens EV affinity for cells of origin to deliver regenerative miRNAs and proteins to muscle, neural, and immune tissue; preclinically suppressed p16 and p21 and reduced inflammation, targeting multiple hallmarks of aging simultaneously.
Johns Hopkins–Suninflam (Baltimore, MD & San Francisco, CA) — SIF001, a second-generation monoclonal antibody against Galectin-3 (Gal-3), aimed at subclinical Alzheimer’s/MCI. Mechanism: a dual immune/inflammation-and-aggregation approach — blocks Gal-3-mediated chronic inflammation, inhibits Gal-3 oligomerization to prevent amyloid-beta aggregation, and disrupts monocyte/macrophage activation and regulatory T-cell suppression, targeting a shared upstream driver of age-related inflammatory dysregulation.
Longeveron Inc. (Miami, FL; Nasdaq: LGVN) — Laromestrocel (Lomecel-B), an allogeneic bone-marrow-derived mesenchymal stem cell (MSC) therapy for aging-related frailty and Alzheimer’s. Mechanism: a pleiotropic MSC effect — pro-vascular, immunomodulatory, and tissue-repair actions, plus paracrine anti-inflammatory signaling, neuroinflammation suppression, and mitochondrial transfer to damaged cells; positioned to counter “inflammaging” across multiple conditions at once.
Minicircle (Austin, TX) — A non-viral plasmid (“minicircle”) gene therapy delivering two gene cassettes, follistatin (FST) and klotho (KL), by subcutaneous injection. Mechanism: follistatin inhibits myostatin/activin signaling to build muscle and reduce inflammation; klotho modulates FGF23 signaling for systemic anti-aging and neuroprotection — delivered via a transfection reagent-complexed episomal plasmid to avoid viral-vector cost and complexity.
NYC-Vita (Mount Sinai, New York, NY) — A randomized trial combining low-dose rapamycin, spermidine, and structured HIIT/resistance exercise in adults 50–90, with deep multi-omics phenotyping. Mechanism: rebalances aging macrophages to cut chronic inflammation while targeting metabolic, muscle, and cognitive decline — rapamycin inhibits mTOR and suppresses the SASP; spermidine restores autophagy and reduces aging-driven myelopoiesis; home-based exercise drives tissue repair.
Mitochondrial All Stars (Mighty Therapeutics + University of Washington Nathan Shock Center; Needham, MA & Seattle, WA) — Repurposing elamipretide (SS-31 peptide), described as the first and only FDA-approved mitochondria-targeting peptide, as a healthspan intervention. Mechanism: binds cardiolipin in the inner mitochondrial membrane to stabilize/improve mitochondrial function, with associated benefits to brain and muscle function and reduced inflammation markers.
RETRO-EPIGERNA (Macau University of Science and Technology, China) — The KYN Composite Capsule, combining medicinal/edible Chinese herbs and probiotics, built on a discovery linking a specific tRNA epitranscriptional modification to aging. Mechanism: restores that tRNA modification to improve translational fidelity and proteostasis, mitochondrial function, and immune resilience — framed as a multi-system route to reversing aging.
RPRGAON / PRG S&Tech — Progerinin (Busan, South Korea) — Progerinin, a small molecule developed originally for Hutchinson-Gilford Progeria (HGPS), now aimed at general aging. Mechanism: inhibits the progerin–lamin A interaction to drive selective progerin degradation, restoring nuclear membrane/lamina architecture and reversing markers of cellular senescence and genomic instability (progerin also accumulates in normally aging arteries, muscle, and fat).
TIME TRAVELER — Plant-EVs (TIME TRAVELER Corp., Tokyo, Japan) — Parsley-derived plant extracellular vesicles (P-EVs), taken as a dietary supplement (“exofull FUJI”), screened from 140+ edible plant species. *Mechanism:*selected for anti-inflammatory and anti-senescence properties; a proprietary non-thermal, low-stress extraction (“FROZEN-TT01”) preserves purity and biological activity, intended to mitigate age-related declines in muscle strength and physical function.
A quick pattern across the ten: three broad mechanistic camps dominate — combination pharmacologic/lifestyle protocols targeting mTOR/AMPK/NAD+ (AgelessRx, NYC-Vita), cell- and vesicle-based regenerative therapies (Goda Lab, Longeveron, TIME TRAVELER), and targeted molecular interventions against a specific aging driver (Johns Hopkins–Suninflam’s Gal-3, Progerinin’s progerin, Minicircle’s follistatin/klotho, Mitochondrial All Stars’ cardiolipin, RETRO-EPIGERNA’s tRNA modification).
Full report for free download:
