Healthspan Weekly — Mar 20, 2026

Two numbers are reshaping how the longevity field thinks about itself this week: an estimated 50% heritability of intrinsic lifespan and $144 million in public funding. The first is a revised estimate of how much genes contribute to lifespan — roughly double what many researchers assumed — reported in a Science paper now in a viral moment. The second is ARPA-H's new commitment to validate aging biomarkers and run human geroprotector trials, which is less a single research grant and more the construction of regulatory validation infrastructure the field has never had. Between them, the message is clear: population genetics may play a larger role in lifespan than previously estimated, the tools to intervene are closer than we hoped, and the infrastructure to test them in humans just received its largest public investment yet.

• Censavudine (TPN-101) Aging Trial — ARPA-H Award (Brown University / University of Rochester): Up to $22M federal award to test whether this HIV reverse-transcriptase inhibitor can suppress retrotransposon activity and reduce biological aging in a 200-person, 48-week randomized trial in healthy adults aged 60–65.
• ARPA-H $144M Geroscience Program (ARPA-H): Funds teams validating surrogate biomarkers and running human trials of candidate geroprotectors including rapamycin — the largest U.S. government push to develop validated pathways for treating aging as a modifiable condition.
• Multi-Modal Gerotherapy Pilot Trial (NCT07475546) (Phase 4 RCT): Testing combination stacks — B12, naltrexone, metformin, NAD+ (and an arm adding rapamycin and glutathione) — in 30 subjects over 90 days, with estimated completion April 2026.
• Rapamycin Genoprotection Study (Published January 2026): Demonstrated that low-dose rapamycin enhances DNA stability in human immune cells by reducing p21, revealing a previously unrecognized genoprotective mechanism.
• Entourage AI Proteomic Aging Clock (Entourage AI, Glasgow): $5M pre-seed raise and preorder launch of proteomics-based biological age and organ health products — organ-specific aging measurement for consumers and clinics.
• Life Biosciences FDA Clearance (Life Biosciences): First FDA clearance for a human cellular reprogramming trial, targeting two age-related vision diseases — partial epigenetic reprogramming enters people.

For years, the consensus was comfortable: many estimates placed genetic contribution to lifespan at roughly 20%, so lifestyle interventions were seen as the main leverage. A Weizmann Institute team led by Ben Shenhar in Uri Alon's lab reports a different picture. Their paper in Science, published January 2026 and now hitting its viral moment, found that when you strip out extrinsic causes of death — accidents, infections, violence — the heritable contribution to lifespan rises to an estimated ~50% (a population-level heritability estimate). The team used three Scandinavian twin registries and U.S. centenarian sibling data, building "virtual twin" models to mathematically separate external mortality from intrinsic aging biology. (For the full analytical framework, see Shenhar et al..)

The critical nuance getting lost in headlines: "50% heritable" does not mean "50% determined by genes." Heritability is a population-level statistic that assumes genetic and environmental influences are separable — which biological systems never fully are. Commentators publishing directly in Science argue the estimate reflects specific historical Scandinavian cohorts, not a universal law. Your choices and environment still matter enormously.

What changes if this holds: longevity genetics research gets a much stronger funding mandate. Polygenic risk scores for aging, genome-wide association studies targeting longevity phenotypes, and family-history-informed prevention all become more defensible investments. If it doesn't replicate in diverse modern populations, the number likely shrinks and the field may return to a lifestyle-first framing. The signal to watch: whether Hevolution, the National Institute on Aging, and ARPA-H shift grant priorities toward genetics-focused aging programs in the next funding cycle.

The U.S. Advanced Research Projects Agency for Health committed $144 million to fund teams validating aging biomarkers and running pragmatic human trials of candidate geroprotectors — rapamycin among them. This is not a single trial; it is building validation infrastructure for surrogate endpoints: composite functional measures, walking speed, validated methylation panels, and wearable-derived endpoints that regulators might eventually accept as surrogates for "aging slower."

Why this is the week's most consequential development, even if it doesn't have the sexiest headline: the longevity field's central bottleneck isn't ideas — it's that proving a drug slows aging in humans currently requires waiting decades for mortality data. If ARPA-H's biomarker validation succeeds, trials that once needed 20-year follow-ups could deliver meaningful readouts in 2–3 years. That would change the economics of every geroprotector in development. If it fails — if the surrogate endpoints don't correlate with hard outcomes — the field stays stuck in the same translational gap. Watch for interim concordance data from funded studies; any positive signal will likely trigger a wave of private investment and new Phase 2–3 trial designs.

A cover article in Aging-US from Cameron Kato and Irina Conboy at UC Berkeley, resurfacing widely this week, reports that combining oxytocin with an Alk5 inhibitor — a compound blocking a receptor tied to age-related tissue decline — produced an approximately 70% increase in lifespan in frail, elderly male mice in that experimental cohort while improving overall health markers.

The headline number is extraordinary. The real story is what happened in the other half of the study: female mice did not experience the same lasting benefits. The authors state the findings "emphasize the differences in aging and in response to longevity therapeutics between the sexes." This is not an asterisk — it's a structural problem. Most mouse longevity studies use males; most human trials don't adequately stratify by sex. If a 70% median lifespan increase only occurs in one sex in mice, that's not evidence of a universal therapy; it's a reminder that aging biology is sex-specific in ways the field hasn't fully reckoned with.

What to watch: whether Conboy's lab advances this toward a clinical design, and — more broadly — whether upcoming conference presentations on rapamycin, senolytics, or NAD+ precursors include sex-disaggregated outcomes. If they don't, the field hasn't learned the lesson this paper is teaching.

Standard CRISPR cuts DNA — precise but permanent and not without risk. A different class of tools, epigenetic editors, silences genes by adding chemical tags to DNA without altering the sequence. Think of it as placing a sticky note over a line of text rather than deleting the words. A Science paper trending heavily this week describes CHARM — Coupled Histone tail for Autoinhibition Release of Methyltransferase — a compact epigenetic editor that silenced prion protein expression across the mouse brain via systemic AAV injection, then turned itself off through a built-in self-silencing mechanism.

The pipeline is moving faster than most realize. Sangamo Therapeutics has shown prion-protein suppression in primates and is planning a human trial in the UK. Genentech paid $50 million upfront — with up to $1.9 billion in milestones — to license a related zinc-finger repressor targeting tau, the protein central to Alzheimer's. Separately, researchers have applied CRISPR-dCas9 epigenome editing to silence tau in human neurons, observing sustained suppression 14 days post-treatment.

The unsolved problem remains delivery: getting these editors into the human brain safely and at therapeutic scale. The self-silencing design addresses the field's biggest safety concern — long-term off-target expression. If IND applications from the Broad Institute or longevity biotechs advance this year, the delivery bottleneck may be loosening. If they stall, AAV tropism and dosing remain harder than the mouse data suggest.

Dasatinib plus quercetin — the most talked-about senolytic cocktail in biohacking circles — just received a serious safety flag. University of Connecticut researchers published in PNAS that giving D+Q to healthy mice caused significant white matter injury, specifically damaging oligodendrocytes that produce myelin, the insulating sheath around neurons.

This is the opposite of neuroprotection. The finding doesn't invalidate senolytics as a concept, but it undermines the assumption that systemic senolytic dosing is uniformly safe across tissues. Brain compartments may respond very differently from peripheral organs. The practical implication for anyone self-experimenting: systemic D+Q protocols that look benign based on blood markers or joint function may be producing invisible CNS damage that won't manifest for years.

The field's response will be telling. If this accelerates development of tissue-targeted senolytics and cell-type-specific delivery — local injections, engineered selectivity — it's a productive correction. If it gets ignored because parts of the biohacking community resist the findings, that's a worse outcome. Watch for whether any regulatory body issues guidance and whether the PEARL rapamycin trial or future senolytic studies add neuro-safety readouts.

Science rarely pauses to ask whether it's optimizing for the right thing. An editorial published March 10, 2026 in Aging-US — "Healthy life extension: Geroscience's north star" — argues the field should measure success by health-adjusted survival, not lifespan alone. Author David Barzilai, writing in honor of the late Mikhail Blagosklonny, reviews data showing life expectancy gains have outpaced healthy life expectancy gains and calls for trials with endpoints that reflect quality of life and independence rather than biomarker shifts.

This matters as a direct challenge to the field's incentive structure. A trial that improves a biological age clock reading by two years but adds two years of frailty is, by this standard, a failure. The editorial calls for "moonshot"-level commitment: larger basic programs, clinical trials with health-adjusted survival endpoints, and translational pipelines that pair mammalian lifespan data with human functional outcomes. If ARPA-H's biomarker validation work adopts this framing — composite functional scores, walking speed, independence metrics — the editorial's argument will have won. If the field keeps chasing clock numbers disconnected from function, it will not.

New findings reported by Fight Aging! identify IGFBP7 — a molecule secreted by senescent cells — as a molecular brake on exercise adaptation. In UK Biobank analyses, lower IGFBP7 levels tracked with reduced mortality and fewer age-related diseases. The researchers propose IGFBP7 as a mediator that blunts the physiological benefits of training in older adults, connecting two active areas: senolytics and exercise science.

This is preprint-level evidence — not peer-reviewed — so treat it as signal, not settlement. But if validated, it reframes senolytics not just as standalone interventions but as potential exercise amplifiers. A review in The Journal of Physiology already positions exercise as a "natural senolytic" and senolytics as targeted boosters for contexts like frailty and sarcopenia. If the IGFBP7 finding replicates, expect trials combining structured exercise with intermittent senolytic dosing — and expect the D+Q white-matter paper to make everyone more cautious about which senolytic they choose.

A mouse whose oxytocin cocktail added about 70% more life but only if he's male, a $144 million government bet that walking speed might be the new cholesterol, and an epigenetic editor that silences a brain disease gene and then politely fires itself.

Somewhere a biohacker is washing down his dasatinib-quercetin stack with airline coffee brewed from water that earned a D rating — and his myelin is filing a grievance with no one.

Stay curious, stay skeptical.

If someone you know is optimizing their longevity stack without reading the safety data, send them this.