A roadmap on research and innovation integrating replacement and next-generation damage-removal therapeutics to modulate the ageing process in the whole body, restore biological function, and extend healthy lifespan.
https://www.nature.com/articles/s43587-026-01138-7
Abstract:
Different species age in similar ways but their lifespans differ by orders of magnitude. It is not clear how these similarities and differences arise from the accumulation of damage that underlies aging. Does long lifespan arise from reduced damage production, increased removal or enhanced robustness to damage? Here we apply the saturating removal model—a stochastic model of damage accumulation and removal—and fit it to survival data from well-studied species. Several parameters have near-universal values including ratios of removal rate, noise amplitude and death threshold. The model parameter that best predicts lifespan is the damage production rate, which spans seven orders of magnitude. We identify two distinct aging regimes: ballistic aging where damage production outpaces removal, characterizing yeast, nematodes, flies and mice, and quasi-steady-state aging, where damage tracks a moving set point of balanced production and removal, characterizing humans, dogs, guinea pigs and cats. These results provide a mechanistic model-based basis of comparative aging that awaits experimental validation.
https://a4li.org/wp-content/uploads/2026/06/MDTD_Whitepaper.pdf
The FDA has several accelerated pathways, and the Alliance for Longevity Initiatives has proposed a new pathway for investigational therapies intended to address biological mechanisms common to two or more serious age-related chronic diseases.
Some companies within this field plan to move through a stepping-stone approach of expanding indications, but the proposed MDTD pathway would streamline the process of targeting multiple pathologies.
Section 6 addresses potential objections to such a pathway.
Link to journal article: https://www.cell.com/cell/fulltext/S0092-8674(26)00587-8
Senate Resolutions (SR) don't become laws, but they can be introduced to express the opinions and sentiments of the chamber. SR 104 was unanimously approved. Here's a snippet:
>Resolved by the Senate of the State of California, That the Senate supports targeting the biological processes of aging as a strategy to prevent or delay the onset of chronic disease; and be it further
>Resolved, That the State of California should invest in research grants, public-private partnerships, and regulatory frameworks that support the development of therapies that slow, prevent, or reverse aspects of biological aging; and be it further...
It was crafted and presented by lawmakers who consulted with the Alliance for Longevity Initiatives (A4LI).
Abstract: Alzheimer’s disease (AD) is not an inevitable outcome of pathology but a dynamic process shaped by how brain cells respond to amyloid-β (Aβ) and tau. To disentangle these responses, we combined spatial transcriptomics and single-nucleus RNA sequencing of the superior frontal cortex from octogenarians living with or without dementia and from cognitively intact centenarians with comparable Aβ accumulation. We identified six distinct tissue domains representing a spatial pathological continuum of AD, with a key inflection point marked by a shift from Aβ-associated inflammatory changes to tau-associated cellular programs. This transition was accompanied by a change in microglial states, from early inflammatory to late antigen-presenting phenotypes, termed early and late plaque-induced gene (PIG) programs. Resilient individuals showed distinct pathological patterns: octogenarians without dementia lacked late PIGs, whereas centenarians showed late PIG activation that was uncoupled from tau accumulation. Together, these findings highlight divergent resilience-associated mechanisms in human aging and position microglial state transitions at the Aβ−tau interface as candidate points of resilience with potential therapeutic relevance.
The company is repurposing a currently-approved drug (undisclosed) as a topical serum to reverse grey hair by increasing stem cell resilience and restoring the ability to differentiate into melanocytes to color hair follicles. The presentation includes the planned timeline for trials and fundraising.
Dr. Irit Rappley holds a PhD in neuroscience and worked for Bristol Myers Squibb.
TLDR:
Step 1: Sign the A4LI proposal to maintain NIH/NIA funding and implement greater focus/coordination with aging biology. This will help them as they engage with members and staff of Appropriations Committees.
Step 2: Find your House and Senate officials here, and use their contact pages to urge maintaining funding for ARPA-H and NIH/NIA, as well as a greater aging biology focus in NIH. Feel free to use the sample below, and contact them weekly over the next few months as budgets and appropriations are debated.
Dear Member of Congress and Staff,
The 2027 Executive budget proposal contains a $555 million (37%) cut to ARPA-H, which would be disastrous for US medical breakthroughs. ARPA-H funds research for bold medical innovation to maintain and restore health in costly pathologies and disabilities, such as neurodegeneration, osteoarthritis, blindness, and more. Cures for these conditions are essential to an aging country. I urge you to protect ARPA-H's $1.5 billion budget and preferably increase it.
The proposed cuts to NIH and NIA (National Institute on Aging) would also be harmful to US health and medical research. To improve impact and efficiency, please advocate for a disease-burden funding allocation, as well as establishing more aging biology consortia to work with major NIH institutes, as the existing Onco-Aging Consortium does. Such a proposal from the Alliance for Longevity Initiatives (A4LI) uses current funding levels, which must be protected: https://a4li.org/wp-content/uploads/2026/05/realigning_for_impact.pdf
Please maintain or increase funding for ARPA-H, NIH, and NIA, and advocate for A4LI's high-impact framework to expand and integrate aging biology research.
Sincerely,
Your Constituent
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Additional background:
Last year, the White House also proposed significant cuts to ARPA-H and NIH, but Congress appropriated similar funding levels as previous years. Contacting your elected officials helps make a difference. For 2027, the Trump administration is again proposing a decrease of $555 million or 37% to ARPA-H, as well as smaller cuts to NIH and different funding/organizational structures. While it's true there are other problems such as staffing shortages, protecting against funding cuts is a necessary first step. ARPA-H is funding critical research programs on aging, such as FRONT by the scientist who wrote Replacing Aging, and PROSPR by a scientist from the Longevity Biotech Fellowship. Other programs like NITRO, THEA, BIOGAMI, and many more also align with the goals of medically targeting aging, especially through repair and replacement. Severe reductions in the ARPA-H budget would hamper opportunities for medical breakthroughs.
The A4LI proposal for NIH and NIA would replicate the Onco-Aging Consortium that connects aging and oncology via the NIA and NCI (National Cancer Institute) for seven other institutes within NIH, which would integrate and amplify aging biology research into the larger research organizations. The proposal operates with maintained funding levels for NIH.
The study will enroll 720 participants in a two-year, randomized, double-blind Phase 3 clinical trial. The lead investigator discusses study design, primary and second outcomes, and other aspects of the study in the presentation.
Later today, Tarek Mouhieddine, MD (u/Myeloma_Doc) of Dana-Farber Cancer Institute in Boston will answer questions in this post. For more information:
>Dr. Tarek Mouhieddine is a physician–scientist and clinical investigator whose research focuses on understanding mechanisms of resistance to myeloma therapies, including CAR T cell therapy and bispecific antibodies, and developing novel therapeutic strategies to improve patient outcomes. He has a strong background in lab-based and translational research, with expertise in tumor genomics and the immune microenvironment. Dr. Mouhieddine is passionate about advancing precision cancer care, the early detection and interception of blood cancers, and translating laboratory discoveries into first-in-human phase I clinical trials in multiple myeloma.
Conflict of interest statement: Dr. Mouhieddine also co-founded a company that partners with GRAIL/Galleri, a multi-cancer early detection test, and Prenuvo, offering whole body MRI scans.
(For some background reading on Galleri, Eric Topol wrote a somewhat critical post, while Christin Glorioso was more positive.)
There will soon be an AMA with oncologist Tarek Mouhieddine, MD of Dana-Farber Cancer Institute in Boston, MA: https://www.dana-farber.org/find-a-doctor/tarek-mouhieddine
Please write your questions as comments on this post so that you don't have to be available at a specific time of the AMA. Here are a few questions to start:
Have you attended talks, read papers, or interacted with other researchers who are part of or have an interest in medical research targeting aging biology?
In what ways is cancer related to the biology of aging, and in what ways is it not?
Geroscience emphasizes prevention and early detection to ideally medically intervene before severe pathology develops. How does this relate to oncology?
Conflict of interest statement: Dr. Mouhieddine also co-founded a company that partners with GRAIL/Galleri, a multi-cancer early detection test, and Prenuvo, offering whole body MRI scans. (For some background reading on Galleri, Eric Topol wrote a somewhat critical post, while Christin Glorioso was more positive.)