The Core Question

We’ve explored space. We’ve peered into black holes. We’ve mapped the genome. We’ve replaced human organs. Yet one of the most fundamental questions remains unanswered: how does the very environment in which all life on Earth evolved continue to shape our aging? For millions of years, the same unseen forces – gravity, atmosphere, magnetism, and temperature – have defined the limits and possibilities of life itself.

The focus of our hypothesis is gravity – a constant that subtly shapes our cells, our bodies, and our brains. We’re investigating how lifelong upright posture under gravity may cause small but cumulative reductions in brain perfusion, leading to microvascular loss in critical regions that regulate systemic aging. What if we could understand this process and potentially reverse it?

Outlined below are research studies and questions to empirically validate or invalidate the mechanistic links proposed in the Gravity-Aging Hypothesis.

Studies that we’ve commissioned:

These foundational studies will address critical gaps in our understanding of the relationship between gravity, neurovascular function, and aging:

1. How does acute daily exposure to microgravity-like environments alter capillary density in basal brain nuclei, and how does this relate to lifespan and healthspan outcomes in murine mammals?
2. What age-associated microvascular changes emerge in basal brain regions in murine mammals, cross-sectionally and longitudinally?
3. Which basal brain regions show the steepest perfusion drop in upright posture when measured with high-resolution MRI?
4. Does chronic reduction in CBF drive capillary rarefaction or BBB compromise in the brainstem and hypothalamus?

Studies that we want to commission:

This framework is suggestive, and not exhaustive. Researchers are invited to explore related or emergent questions.

1. How might precisely timed artificial gravity/microgravity cycles optimize neurovascular health through adaptive angiogenesis and hormetic mechanisms?
2. What is the quantitative contribution of declining cerebral perfusion pressure versus systemic arterial stiffening and endothelial dysfunction to age-related hypertension, and can these mechanisms be experimentally dissociated?
3. Is capillary rarefaction in the aging brain primarily driven by chronic cerebral hypoperfusion, or by intrinsic endothelial and pericyte senescence that secondarily reduces perfusion capacity?
4. Do varying gravitational mechanical loads differentially modulate HIF-1α, VEGF, and eNOS pathway activation in cerebral endothelium, and do acute (hours) versus chronic (weeks-months) exposure paradigms show divergent adaptive or maladaptive responses?
5. Does modulating regional cerebral blood flow through pharmacological (nitric oxide donors, ACE inhibitors, or targeted vasodilators) or mechanical interventions independently of gravitational load alter the progression or reversal of established hallmarks of aging?
6. In individuals with orthostatic hypotension versus controls, which brain regions show the steepest posture-induced CBF drop?
7. An estimated 40-50% of human metabolism is spent just fighting gravity. Does the aging body sacrifice cerebral blood flow to maintain anti-gravity compensation as energy reserves deplete?
8. What is the temporal sequence of BBB disruption, endothelial senescence, pericyte loss, and regional CBF decline during aging, and does this sequence differ between the brainstem/hypothalamus and other regions of the brain?
9. Do males and females show differential susceptibility to gravity-induced cerebral hypoperfusion and capillary rarefaction during aging, and does sex-specific preservation of neurovascular function account for documented longevity advantages in females?
10. Can brief sessions of safe head-down tilt (HDT) reduce mild hypertension by reducing the compensatory pressure needed to maintain brain blood flow?
11. How does cerebral blood flow (CBF) change with age in murine mammals, and does this decline correlate with progressive microvascular rarefaction in vulnerable brain regions?

For Researchers

Funding applications are open to academic and non-profit researchers worldwide. We particularly welcome proposals from scientists in adjacent fields, such as neurovasculature, brain aging, and gravitational biology, whose expertise could uncover new dimensions of this research area.

Visit Continue for Researchers to know more and apply for funding.