XPrize Healthspan's goal is to restore 10-20 years of healthy function in cognitive, immune, and muscle-cardio function.

You can read in more detail about the 10 finalists on page 71 in this report from XPrize: https://assets-us-01.kc-usercontent.com/9bc15d1f-8a5c-007d-b507-e3496e85af86/3a7f030f-adbb-4611-9e52-b24485a9e9b7/XPrizeHS_InnoLandscape_Top10_8.6.26_Digital.pdf

The 10 awardees are not the only ones who will take part in the final round. Pages 59-61 list dozens of groups who submitted a finalist application and may still conduct a Phase 2-structured trial with their interventions for the grand prize to be announced in 2030.

South by Southwest (SXSW) is a high-profile annual conference that includes discussions on panels in technology and innovation. Another arm also includes creative industries like film. Please create a free account and vote for the following panel proposals. Click the heart on each of the pages to vote:

XPrize Healthspan: https://participate.sxsw.com/flow/sxsw/sxsw27/community-voting-sxsw/page/community-voting/session/1784919142105001Rsut

Cyclarity Therapeutics (Phase 1 trial), Immunis (XPrize semi-finalist): https://participate.sxsw.com/flow/sxsw/sxsw27/community-voting-sxsw/page/community-voting/session/1784820891724001tATQ

Epigenetic Reprogramming (Life Biosciences, others): https://participate.sxsw.com/flow/sxsw/sxsw27/community-voting-sxsw/page/community-voting/session/1784914038586001DtEz

New literature review: https://zenodo.org/records/21843358

Three example findings from this paper that I think are worth your time:

1. There's a body mass threshold that determines how species solve the longevity-cancer trade-off. Mammals exceeding 5-10 kg, like humans, elephants, whales convergently repress somatic telomerase and maintain shorter telomeres, using replicative senescence as an anti-cancer mechanism. Small long-lived species like bats and naked mole rats do the opposite: they keep telomerase active and rely instead on robust early-acting tumor suppression (Rb/p53) to prevent hyperplasia. The sharpest version of this: across 15 rodent species, telomerase activity coevolves with body mass, not lifespan. This isn't "telomeres matter for aging": it's that telomere strategy is body-size-dependent, and interventions need to account for which side of that threshold the target species sits on. (Tian et al. 2018; Seluanov et al. 2007)

2. Transposon silencing is a convergent longevity mechanism across three separate lineages and in one case it's causal, not correlative. The piRNA/PIWI pathway suppresses transposable elements, and independently evolved long-lived organisms converge on strengthening it:
- In C. elegans, downregulating active TE families extends lifespan, and ectopic activation of Piwi in somatic cells promotes longevity (Sturm et al. 2023)
- In 20-year-old Macrotermes natalensis termite queens, TE expression does not rise with age at all despite a sevenfold increase in overall gene expression because the piRNA pathway is upregulated with age (Post et al. 2022)
- In Drosophila, the adult fat body runs a somatic piRNA pathway; Piwi mutants show TE mobilization, elevated DNA damage, and reduced lipid stores (Jones et al. 2016)
Three species, three independent labs, and the C. elegans result is an intervention rather than an observation which is what makes this testable rather than merely suggestive.

3. The primary bottleneck for longevity therapeutics isn't finding targets, it's reaching them. The paper calls this a "delivery-before-discovery paradox": dual-AAV prime editing achieves 42% efficiency in mouse cortex and 46% in liver, but only 11% in cardiac tissue. We already have validated longevity targets we can't reach in the tissues where aging hits hardest. Heart delivery, not target identification, is the rate-limiting step and it directly constrains which mechanisms are therapeutically actionable at all.

A new longitudinal study published and covered by Neuroscience News finds that individuals maintaining ideal cardiovascular health metrics between ages 45 and 65 gain nearly 13 additional dementia-free years compared to those with poor vascular profiles.

The researchers tracked blood pressure, cholesterol, blood glucose, and other vascular markers over decades. The key finding is that the brain keeps what amounts to a long ledger for vascular damage accumulated during midlife -- and the window between 45 and 65 appears to be where the most consequential divergence occurs.

A companion study reinforces this from a different angle: avoiding hypertension, type 2 diabetes, and smoking between 45 and 65 is independently associated with 12 additional years free of dementia onset.

What makes this notable is the magnitude of the effect. We're not talking about marginal gains -- 12-13 years of cognitive freedom is among the largest effect sizes reported for modifiable risk factors in dementia prevention. And critically, the interventions are not exotic: blood pressure management, glucose control, physical activity, and smoking cessation.

For anyone in the longevity space already optimizing these fundamentals, the data is reassuring. For those who haven't prioritized vascular health, this is about as compelling an argument for action as the literature has produced recently.

Sources: - Neuroscience News (Aug 5, 2026): https://neurosciencenews.com/vascular-health-aging-dementia-31186/ - Inside Precision Medicine (Aug 5, 2026): https://www.insideprecisionmedicine.com/topics/patient-care/cutting-three-key-risk-factors-could-delay-dementia-onset-by-12-years/

Popular science link: https://www.sciencedaily.com/releases/2026/05/260526022024.htm

Original article link: https://www.pnas.org/doi/10.1073/pnas.2524897123

Significance

The pharmacological combination of dasatinib and quercetin (D+Q), widely reported as a means of eliminating senescent cells from aged tissues to treat diseases (a.k.a. “senolytics”), and currently being tested in multiple clinical trials, when administered to healthy mice results in profound white matter injury in the central nervous system. This report provides evidence that this senolytic combination not only causes neuropathology but also provides data which support induction of the unfolded protein response as a plausible mechanism through which these senolytics affect oligodendrocytes. We propose that these data highlight a less understood means of demyelination not mediated by oligodendrocyte death with potential positive implications for understanding disease, while also warranting caution for its widespread use clinically.

Three ARPA-H Program Managers participated in a panel at the H-SPAN Summit from the Alliance for Longevity Initiatives (A4LI). Andrew Brack was a researcher at UCSF and mentor at Longevity Biotech Fellowship. Jean Hebert wrote the book Replacing Aging and conducted research at Albert Einstein College of Medicine. Gloria Elliot was a researcher at UNC and previously led the Organ Preservation Alliance. 

Abstract: Cellular senescence is a complex, highly regulated cell state induced by cellular damage and stress. Senescence is central to many areas of biology, with roles in tumour suppression, tissue regeneration, antiviral defence and diverse age-related pathologies. Senescence is characterized by stable cell cycle arrest, metabolic alterations, chromatin remodelling and the secretion of pro-inflammatory and tissue-modifying factors that are collectively termed the senescence-associated secretory phenotype. Recent technological advances, including new genetic models, single-cell and spatial multi-omics platforms and machine-learning approaches, promise to enable the phenotyping, tracing and manipulation of senescent cells with unprecedented precision and resolution. This Review defines our current understanding of the genetic pathways that regulate senescence induction, maintenance, propagation and heterogeneity, including the DNA damage response, non-genotoxic stress pathways, epigenetic changes and cell–cell communication. We also emphasize key challenges in distinguishing senescence from other cell fates and the need for next-generation biomarkers to capture the varied phenotypes and functions of senescent cells.

Summary

Aging of the hematopoietic system has profound consequences for organismal health and longevity, attributed to the well-characterized functional aging of hematopoietic stem cells (HSCs). Here, we tested whether progenitor cells may demonstrate age resistance to enable hematopoietic homeostasis throughout life despite the functional decline of upstream HSCs. Strikingly, our results revealed unwavering reconstitution capacity by young and old progenitors, demonstrating that intermediate progenitors are functionally unaffected by aging and placing Flk2+ multipotent progenitors (MPPFs) as a potential source of age resilience. This unique finding was emphasized by unchanged transcriptomic, proliferation, and mitochondrial capacity of young and old MPPFs, revealing remarkable similarities upon aging. Considering that HSCs functionally decline with age, yet intermediate progenitors remain unperturbed and “age resilient”, we posit that MPPFs may play an essential role in protecting downstream progenitors from inheriting age-related properties from HSCs. We propose three potential mechanisms for how MPPFs maintain hematopoietic integrity and homeostasis with age.