HoldsUp

FoundMyFitness · 2026-06-10 · Rhonda Patrick (host), Steve Horvath

The 7 Habits of People Who Age Slower | Dr. Steve Horvath

73 claims checked against research: 3 contradicted 7 overstated 6 needing context 52 supported 5 unverified

7

Overstated

0:28:29Steve Horvathoverstatedlow

Randomized controlled trials evaluating supplements and medications have demonstrated that the GrimAge epigenetic clock can be reversed to a minor extent.

"now I'm confident in saying that you can reverse GrimAge to some extent. The keyword is "to some extent" because these changes appear to be very minor. We can talk about it later, but there have been very rigorous randomized control trials with supplements and medications." (said at 0:28:29)

Although preliminary human intervention studies have reported minor reductions in epigenetic age measured by GrimAge, the claim that this has been demonstrated by 'very rigorous randomized controlled trials' is overstated. The primary published clinical trial showing GrimAge reversal using a medication and supplement protocol (the TRIIM trial using recombinant human growth hormone, DHEA, and metformin) was a small, open-label, single-arm pilot study of nine healthy men without a randomized control group. While that trial reported an average 2-year reduction in GrimAge relative to chronological age, large and rigorous randomized controlled trials confirming pharmacological or supplement-induced reversal of GrimAge remain lacking.

1:09:55Steve Horvathoverstatedmoderate

A preprint study led by Michael Corley found that semaglutide-induced weight loss in obese individuals over 33 weeks produced significant rejuvenation across all tested DNA methylation clocks.

"there was a very exciting study um um that involved actually obese people, BMI 30 and higher, who had been put on a GLP-1 receptor agonist treatment, semaglutide. And these people really lost a lot of weight over 33 weeks. And um by the way, this um study um was published in medRxiv. It's a preprint, so um take it with caution. It was Michael Corley's group in San Diego, but very beautiful study, very rigorous again, and um a large sample size, so credible. And they looked at all methylation clocks, and suddenly all methylation clocks picked it up, really all, you know." (said at 1:09:55)

The speaker refers to a study led by Michael Corley and colleagues (initially released as a preprint and subsequently published in Nature Communications). While the study did evaluate semaglutide over a 32-week trial and demonstrated deceleration across multiple second- and third-generation DNA methylation clocks (e.g., PhenoAge, GrimAge, DunedinPACE), several details are overstated or mischaracterized. The study was not conducted in a general obese cohort with a large sample size, but was a post hoc analysis of a phase 2b trial in adults with HIV-associated lipohypertrophy (n = 45 receiving semaglutide vs. n = 39 receiving placebo). Furthermore, significant effects were observed across specific second- and third-generation clocks rather than literally all methylation clocks.

  • partial: Semaglutide slows epigenetic aging in a randomized trial of HIV-associated lipohypertrophy… (Nature communications 2026) · cited 6x in the literature
    "We report a post hoc exploratory epigenetic age analysis of a 32-week, randomized, double-blind, placebo-controlled phase 2b trial (NCT04019197) of semaglutide in adults with human immunodeficiency virus (HIV)-associated lipohypertrophy (semaglutide n = 45; placebo n = 39)... In adjusted analyses, semaglutide reduced epigenetic aging across multiple second- and third-generation clocks, including PhenoAge (-4.9 years/year, p = 0.004), PCGrimAge (-3.1, p = 0.007), GrimAge V2 (-2.3, p = 0.009), OMICmAge (-2.2, p = 0.009), RetroAge (-2.2, p = 0.030), and DunedinPACE (-0.09 units, 9% slower, p = 0.01)." (abstract, results, passage verified)
    pubmedfull study (doi)
1:13:58Rhonda Patrick (host)overstatedhigh

In the COSMOS trial, daily multivitamin (Centrum Silver) supplementation over 3.6 years slowed global cognitive brain aging by 2.1 years and episodic memory aging by almost 5 years compared to placebo.

"And it was What is it, about 3.6 years for this trial, and they were looking at I mean, there's a lot of endpoints of this trial, but one of them was cognitive function and brain aging. And at the end of the trial, the the people that were given the multivitamin had slowed their brain aging by 2.1 years... episodic brain aging... that was slowed by almost 5 years compared to the placebo group" (said at 1:13:58)

Data from the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) cognitive substudies (COSMOS-Mind, COSMOS-Web, and COSMOS-Clinic) evaluated daily multivitamin supplementation (Centrum Silver) in older adults. Across a meta-analysis of non-overlapping participants from all three COSMOS cognitive substudies, daily multivitamin supplementation demonstrated statistically significant benefits for both global cognition and episodic memory, with the overall effect equivalent to reducing cognitive aging by approximately 2 years. Individual substudies estimated global cognitive slowing of about 1.8 years (COSMOS-Mind) and episodic memory improvement equivalent to 3.1 years of age-related change (COSMOS-Web). Claiming that episodic memory aging was slowed by 'almost 5 years' across the trial overstates the overall findings, as effects of that magnitude were observed only in exploratory subgroup analyses of participants with baseline cardiovascular disease.

1:26:32Rhonda Patrick (host)overstatedhigh

In the DO-HEALTH clinical trial cohort of older adults in Switzerland, approximately 88% of participants self-identified as physically active at baseline.

"Did you read that the the the starting population, 88 like around 88% of them already identified as being physically active?" (said at 1:26:32)

In the DO-HEALTH randomized trial cohort (2,157 older adults aged 70 and older), 83% of the overall study population was characterized as physically active at baseline, while 66.7% of participants in the Swiss cohort met physical activity recommendations (≥150 min/week moderate or ≥75 min/week vigorous physical activity). The figure of 88% (1,900 out of 2,157 participants) actually refers to the proportion of participants who completed the 3-year trial, rather than the proportion who were physically active at baseline in Switzerland.

1:31:10Rhonda Patrick (host)overstatedlow

Vitamin D deficiency causes biological age acceleration of up to 3 years, and correcting deficiency slows or reverses this age acceleration.

"showing that vitamin D deficiency causes age acceleration, in some cases severe, like 3 years. And if you correct that deficiency, it'll slow age acceleration where then you say, you know, reversed aging by, you know, not four years or whatever." (said at 1:31:10)

Observational and quasi-experimental studies, such as the Berlin Aging Study II (BASE-II/GendAge), have reported that vitamin D deficiency is associated with accelerated epigenetic aging, and individuals who initiated vitamin D supplementation exhibited a 1.3- to 2.6-year lower epigenetic age acceleration compared to untreated deficient individuals. Additionally, a small randomized trial in 51 adults found that 16 weeks of vitamin D3 supplementation was associated with an approximately 1.85-year reduction in Horvath epigenetic age. However, framing this relationship as proven causation and stating that supplementation robustly slows or reverses aging by 3 to 4 years overstates the literature. The primary evidence of multi-year differences comes from observational or self-selected quasi-interventional cohorts, while larger randomized trials (such as the DO-HEALTH trial) show much smaller or clock-dependent effects.

1:35:10Steve Horvathoverstatedlow

In postmenopausal women from the Women's Health Initiative, circulating blood carotenoid levels have an inverse correlation of approximately -0.3 with GrimAge and other epigenetic clocks.

"You can measure the so-called carotenoid levels in the blood and and have an objective readout of fruit vegetable consumption. And the striking finding in postmenopausal women from the Women's Health Initiative was that this um measure of vegetable intake has a strong correlation with GrimAge and other epigenetic clocks. Strong meaning maybe minus 0.3." (said at 1:35:10)

A 2017 cross-sectional analysis of 4,173 postmenopausal female participants from the Women's Health Initiative (WHI) evaluated blood carotenoid levels as an objective marker of fruit and vegetable consumption against epigenetic clock metrics (PMID 28198702). The study found a statistically significant inverse association between blood carotenoid levels and extrinsic epigenetic age acceleration (EEAA; p = 1 × 10⁻⁵). However, the claim overstates the magnitude and specificity of this relationship. First, GrimAge was not published until 2019, and the 2017 WHI analysis utilized earlier Horvath epigenetic clock measures (extrinsic and intrinsic epigenetic age acceleration) rather than GrimAge. Second, the correlation magnitude was substantially weaker than claimed: standard correlation coefficients between blood carotenoids and epigenetic age acceleration measures in this dataset are around r = -0.05 to -0.10, not -0.3. Thus, while the inverse association between serum carotenoids and epigenetic aging acceleration in postmenopausal WHI women is supported by the literature, stating a correlation magnitude of approximately -0.3 with GrimAge overstates both the clock used and the strength of the association.

1:37:14Rhonda Patrick (host)overstatedmoderate

Randomized controlled trials show that lutein and zeaxanthin accumulate in the eye and can help prevent age-related macular degeneration.

"if you're talking about carotenoids, you know, lutein, zeaxanthin, these are these are carotenoids that are in greens and interesting, there's been a lot of studies coming out looking at blood levels of lutein and zeaxanthin. People usually associate that them with eye health. They accumulate in the eye. There have been randomized controlled trials showing they can help prevent age-related macular degeneration." (said at 1:37:14)

Lutein and zeaxanthin are well documented to selectively accumulate in the retina and central macula, forming the macular pigment. However, randomized controlled trials (RCTs) have not demonstrated that these carotenoids prevent the primary onset or initial development of age-related macular degeneration (AMD) in healthy individuals. Instead, large multicenter RCTs—most notably the Age-Related Eye Disease Study 2 (AREDS2)—demonstrated that adding lutein and zeaxanthin (replacing beta-carotene in the AREDS antioxidant formula) reduces the rate of progression to late-stage AMD in patients who already have intermediate AMD or advanced AMD in one eye. Conflating secondary prevention of disease progression in affected patients with primary prevention of AMD overstates the RCT evidence.

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.