LongeCityNews Last Updated: 06 December 2025 - 03:29 PM

A new report released by Hevolution Foundation highlights that extending the number of years people live in good health is now one of the defining challenges for economies and societies worldwide.

The second edition of the Global Healthspan Report presents new evidence that aging, once seen as an inevitable decline, can be managed through science, policy, and innovation to drive sustainable growth and wellbeing. Drawing on two global surveys and extensive investment data, the report positions healthspan, the years of life spent in good health, as both a catalyst for scientific and economic progress.

The findings reveal the magnitude of what’s at stake:

• Reducing the period of poor health by just twelve months could generate trillions of dollars annually through higher productivity and lower healthcare costs.
• At the same time, global public demand for healthy longevity is rising fast, with more than half of respondents saying they would spend half their annual income on treatments that could add ten healthy years to their lives.
• Investment in healthspan-related innovation is accelerating. In 2024, global funding for healthspan science nearly doubled to $7.33 billion, with average deal sizes increasing by 77% compared to the previous year. The report argues that this surge signals growing investor confidence in an emerging sector poised to reshape the future of healthcare and aging.

“Extending healthy years of life is one of the defining challenges of our time,” said Dr. Mehmood Khan, CEO of Hevolution Foundation. “This report offers a roadmap for how science, policy, and investment can come together to make that vision real. Through our research funding and biotech investing led from Saudi Arabia, we are helping drive the global shift from simply adding years to life, to adding life to years, ensuring that healthier aging becomes a shared priority for all.”

The report also emphasizes the importance of global collaboration, highlighting how regions such as the Middle East are rapidly emerging as innovation hubs for healthspan science and policy. In Saudi Arabia, this vision aligns with Vision 2030 and the Kingdom’s ambition to become a global center for scientific and health innovation. Through Hevolution Foundation, Saudi Arabia has already allocated about $400 million toward advancing healthspan science, supporting over 230 research grants representing around 200 grantees worldwide, 25 strategic partnerships, and four biotech companies, all progressing toward human clinical translation.

The second edition of the Global Healthspan Report serves as a call to action for policymakers, scientists, and investors to align on a shared goal: extending healthy human lifespan, expanding access to innovation, and ensuring that longer, healthier lives become a global reality.

The full report is available for download at:

https://tinyurl.com/Global-Healthspan-Report-2025

About Hevolution Foundation

Established by Royal Order in 2018 and launched in 2021, Hevolution Foundation is a first-of-its kind global non-profit organization that incentives grants and early-stage investments to accelerate independent research and entrepreneurship in the emerging field of healthspan science. With a focus on aging as a treatable process, Hevolution aims to propel aging and geroscience research forward and support a cutting-edge global ecosystem of talent. Headquartered in Riyadh, Saudi Arabia, with a North American hub in Boston and plans for further international expansion, the Foundation has set key goals and targets to advance its Vision & Mission. Over the last three years, Hevolution has allocated over $400M in funding.

A new review highlights the promise of microglia replacement, a strategy that made the leap from mouse studies to the first successful human trial in just five years [1].

Repair or replace

Microglia, the resident immune cells of the brain, have been implicated in various diseases, including Alzheimer’s [2]. However, treatments modulating microglial behavior are scarce, partly because they hide behind the blood-brain barrier (BBB), which blocks many potential drugs and makes it hard to target them precisely [3].

Replacing defective microglia is an interesting solution, but until several years ago, it sounded like something out of this world. Surprisingly, the required technology has matured fast, making its way from mouse studies to a successful human trial in five years. Now, the team behind these breakthroughs, from Fudan University in China, has published an enlightening review of the field in the journal Cell Stem Cell.

“Microglial gene mutations can either cause or accelerate the course of CNS disorders. Conceptually, replacing pathogenic microglia with gene-corrected or wild-type counterparts offers a promising therapeutic avenue to restore homeostatic function and mitigate disease progression,” said corresponding author and team leader Bo Peng, professor at Fudan University.

Success at a cost

As is the case with many promising but ambitious directions, the team chose a rare and severe disease, adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), as their first target. Like some other primary microgliopathies, ALSP is caused by mutations in microglial genes such as CSF1R. In July of this year, the researchers reported highly encouraging results of microglia replacement in human patients, with a two-year follow-up suggesting that disease progression had slowed or halted.

While done in a small, highly selected cohort, the trial showed that large-scale microglia replacement is possible in humans and can change the trajectory of a devastating microgliopathy. However, it came at a cost.

Microglia replacement is easier said than done. In a healthy brain, microglia form a dense, self-renewing grid. They occupy territories and suppress each other’s proliferation, so newcomers cannot easily move in. Early attempts mostly involved local injections or incomplete depletion and ended up with small patches of donor cells or rapid rebound of the original microglia.

“Even though microglia replacement is recognized for its potential for disease treatment, early approaches in the pre-replacement era lacked an efficient and robust strategy for microglia replacement, which is key for a meaningful and effective therapy,” co-author Junhao Rao said.

Hey, MISTER!

A successful therapy must combine effective clearance of the resident microglia with a strong influx of donor cells. In practice, that means depleting resident microglia simultaneously with myeloablative conditioning similar to what is used before bone marrow transplantation. Conditioning wipes out much of the host’s hematopoietic system and triggers strong chemokine signals in the brain, which invites donor-derived myeloid cells from bone marrow or peripheral blood to enter the CNS and differentiate into microglia-like cells.

This led the researchers to develop Microglia Intervention Strategy for Therapy and Enhancement by Replacement (MISTER), which includes several protocols. In Mr BMT, microglia are replaced using classical bone marrow transplantation. In Mr PB, the donor source is peripheral blood, which is easier on donors and still achieves high levels of replacement (80% compared to 90% for Mr BMT in mice).

Looking into the future

Can this therapy, today or in the future, treat more common diseases? Some genetic mutations have been linked to dementia. Even if they do not cause disease on their own, they can heavily tilt the odds. “TREM2 mutations may not be sufficient to cause Alzheimer’s disease independently, but they can act as pathogenic amplifiers that synergistically drive disease risk,” Peng said, noting that this is just one example; another one would be mutations in APOE, an Alzheimer’s-related gene strongly expressed in glia, including microglia.

However, the authors are careful about the limitations of their approach. Myeloablative conditioning is still a harsh, cancer-level intervention, which currently confines microglia replacement to rare, life-threatening indications. For common neurodegenerative diseases or risk reduction, the risk-benefit balance must be better, especially in frail older patients. The review explicitly points to safer, more targeted conditioning and better control over engineered microglia as key design goals.

If more tolerable protocols are developed, the authors envisage an even broader use for microglia replacement: genetically engineered microglia that essentially work as drug factories, secreting missing lysosomal enzymes, anti-amyloid antibodies, or neurotrophic factors from within the brain. This would turn microglia replacement into a long-lived delivery system behind the blood-brain barrier.

“Overall, microglia replacement is a newly emerging but rapidly progressing field,” Peng said. “Challenges in safety, compatibility, and long-term function remain, yet they represent solvable design targets. With continued mechanistic insight, clinical innovation, and broad collaboration, microglia replacement can mature from early breakthroughs into a generalizable platform across neurological diseases.”

Literature

[1] Peng, B., Rao, Y., & Wu, J. (2025). The evolution of microglia replacement: A new paradigm for CNS disease therapy. Cell Stem Cell, 32(12), 1487–1503.

[2] Hansen, D. V., Hanson, J. E., & Sheng, M. (2018). Microglia in Alzheimer’s disease. Journal of Cell Biology, 217(2), 459-472.

[3] Pardridge, W. M. (2005). The blood-brain barrier: bottleneck in brain drug development. NeuroRx, 2(1), 3-14.