Pair page
FOXO4-DRI with NAD+
Mechanism-tag overlap and published literature for FOXO4-DRI and NAD+, pulled verbatim from each Kalios compound profile. Kalios is a literature reference, not a recommendation.
Mechanism overlap
Mechanism tags are verbatim labels on each compound's profile. Generic tags ("peptide", "small-molecule", "research-chemical") are excluded from this overlap view. Tags are descriptive — not an inference about combined effect.
senolytic-p53-foxo4-interface-disruptor
coenzymemitochondrial-longevity
Co-administration notes from the literature
Verbatim summary text pulled from each compound's profile data. Researchers studying FOXO4-DRI and NAD+ have published these mechanism-level observations. Not a co-administration recommendation.
Different mechanism (mitochondrial substrate / sirtuin support). Frequently combined in community longevity protocols, though mechanistically unrelated and without combination evidence.
Quick facts
FOXO4-DRI
NAD+
Literature table
Classified references from each compound profile. Click a column header to sort. Click a PMID to open PubMed. Findings are quoted verbatim from each profile's literature_summary; nothing here is added or interpreted.
| Year | Compound | Source | Finding |
|---|---|---|---|
| 2019 | FOXO4-DRI | Justice JN, Nambiar AM, Tchkonia T, LeBrasseur NK, Pascual R, Hashmi SK, Prata L, Masternak MM, Kritchevsky SB, Musi N, Kirkland JL. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine. 2019;40:554-563. PMID: 30616998… PMID 30616998 | human pilot |
| 2019 | FOXO4-DRI | Hickson LJ, Langhi Prata LGP, Bobart SA, Evans TK, Giorgadze N, Hashmi SK, Herrmann SM, Jensen MD, Jia Q, Jordan KL, et al. Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney dis… PMID 31542391 | human study |
| 2020 | FOXO4-DRI | Zhang C, Xie Y, Chen H, Lv L, Yao J, Zhang M, Xia K, Feng X, Li Y, Liang X, Sun X, Deng C, Liu G. FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice. Aging (Albany NY). 2020;12(2):1272-1284. PMID: 31959736. PMID 31959736 | preclinical, in vivo |
| 2018 | FOXO4-DRI | Zhao Y, Tyshkovskiy A, Muñoz-Espín D, et al. Naked mole rats can undergo developmental, oncogene-induced and DNA damage-induced cellular senescence. Proc Natl Acad Sci U S A. 2018;115(8):1801-1806. (Comparative senescence-biology context.) | preclinical, in vivo |
| 2025 | FOXO4-DRI | Yu Y, Zhang R, Li Y, et al. FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation. Commun Biol. 2025. DOI: 10.1038/s42003-025-07738-0. (Independent confirmation of senolytic mechanism in keloid fibrobl… | preclinical, in vitro |
| 2021 | FOXO4-DRI | Le H, Cinaroglu SS, Manalo EC, et al. Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes. Front Bioeng Biotechnol. 2021;9:677576. PMC: PMC8116695. | preclinical, in vitro |
| 2025 | FOXO4-DRI | Stryeck S, Baar MP, Brandt RMC, et al. The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI. Nat Commun. 2025;16. DOI: 10.1038/s41467-025-60844-9. (NMR / structural-biology characterization of the FOXO4-DRI binding mode on p53.) | mechanism / discovery |
| 2020 | FOXO4-DRI | Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med. 2020;288(5):518-536. PMID: 32686219. (Senolytics field overview placing FOXO4-DRI in context.) PMID 32686219 | mechanism / discovery |
| 2003 | FOXO4-DRI | Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, Moll UM. p53 has a direct apoptogenic role at the mitochondria. Mol Cell. 2003;11(3):577-590. PMID: 12667443. (Mechanistic foundation for the mitochondrial p53 apoptotic pathway that FOXO4-DRI engages.) PMID 12667443 | mechanism / discovery |
| 2021 | FOXO4-DRI | Le HH, Cinaroglu SS, Manalo EC, Ors A, Gomes MM, Duan Sahbaz B, et al. Molecular modelling of the FOXO4-TP53 interaction to design senolytic peptides for the elimination of senescent cancer cells. EBioMedicine. 2021;73:103646. PMC: PMC8601985. (Computational design of "ES2" pept… | pharmacology |
| 2017 | FOXO4-DRI | Childs BG, Gluscevic M, Baker DJ, Laberge RM, Marquess D, Dananberg J, van Deursen JM. Rejuvenation by Therapeutic Elimination of Senescent Cells. Cell. 2017;169(1):3-5. PMID: 28340347. (Editorial commentary in same Cell issue framing the Baar 2017 paper as a senolytic field mil… PMID 28340347 | pharmacology |
| 2026 | FOXO4-DRI | ClinicalTrials.gov / EudraCT. Search results for "FOXO4-DRI" — no registered trials as of April 2026. (Documentation of the absence of any registered human clinical trial.) | regulatory / registry |
| 2015 | NAD+ | Chen AC, Martin AJ, Choy B, Fernández-Peñas P, Dalziell RA, McKenzie CA, Scolyer RA, Dhillon HM, Vardy JL, Kricker A, St George G, Chinniah N, Halliday GM, Damian DL. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med. 2015;373(17):1618-1626… PMID 26488693 | human trial, Phase 3 |
| 2023 | NAD+ | Katayoshi T, Uehata S, Nakashima N, Nakajo T, Kitajima N, Kageyama M, Tsuji-Naito K. Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial. Sci Rep. 20… PMID 36797283 | human trial |
| 2018 | NAD+ | Dollerup OL, Christensen B, Svart M, Schmidt MS, Sulek K, Ringgaard S, Stødkilde-Jørgensen H, Møller N, Brenner C, Treebak JT, Jessen N. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effect… PMID 30084900 | human trial |
| 2017 | NAD+ | Airhart SE, Shireman LM, Risler LJ, Anderson GD, Nagana Gowda GA, Raftery D, Tian R, Shen DD, O'Brien KD. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy voluntee… PMID 29211728 | human trial |
| 2022 | NAD+ | Brakedal B, Dölle C, Riemer F, Ma Y, Nido GS, Skeie GO, Craven AR, Schwarzlmüller T, Brekke N, Diab J, Sverkeli L, Skjeie V, Varhaug K, Tysnes OB, Peng S, Haugarvoll K, Ziegler M, Grüner R, Eidelberg D, Tzoulis C. The NADPARK study: A randomized phase I trial of nicotinamide rib… PMID 35537443 | human trial, Phase 1 |
| 2019 | NAD+ | Grant R, Berg J, Mestayer R, Braidy N, Bennett J, Broom S, Watson J. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+. Front Aging Neurosci. 2019;11:257. PMID: 31572171. PMID 31572171 | human pilot |
| 2018 | NAD+ | Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, Chonchol M, Seals DR. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. PMID: 29599478. PMID 29599478 | human study |
| 2023 | NAD+ | Vreones M, Mustapic M, Moaddel R, Pucha KA, Lovett J, Seals DR, Kapogiannis D, Martens CR. Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin. Aging Cell. 2023;22(1):e13754. PM… PMID 36448627 | research article |
| 2022 | NAD+ | Freeberg KA, Craighead DH, Martens CR, You Z, Chonchol M, Seals DR. Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Midlife and Older Adults. Front Cardiovasc Med. 2022;9:881703. PMID: 35757350. PMID 35757350 | research article |
| 2021 | NAD+ | Yoshino M, Yoshino J, Kayser BD, Patti GJ, Franczyk MP, Mills KF, Sindelar M, Pietka T, Patterson BW, Imai SI, Klein S. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. PMID: 33888596. PMID 33888596 | research article |
| 2019 | NAD+ | Elhassan YS, Kluckova K, Fletcher RS, Schmidt MS, Garten A, Doig CL, Cartwright DM, Oakey L, Burley CV, Jenkinson N, Wilson M, Lucas SJE, Akerman I, Seabright A, Lai YC, Tennant DA, Nightingale P, Wallis GA, Manolopoulos KN, Brenner C, Philp A, Lavery GG. Nicotinamide Riboside A… PMID 31390667 | research article |
| 2018 | NAD+ | Yoshino J, Baur JA, Imai SI. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018;27(3):513-528. PMID: 29249689. PMID 29249689 | research article |
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Frequently asked
Have FOXO4-DRI and NAD+ been studied together?
Researchers have published mechanistic-level co-administration discussion of FOXO4-DRI and NAD+. No human co-administration trials are catalogued in the Kalios profiles. The pair page lists each compound's classified literature; full citations sit on each individual profile.
What mechanisms do FOXO4-DRI and NAD+ share?
FOXO4-DRI and NAD+ do not share a specific mechanism tag on their Kalios profiles. They appear on the same pair page because at least one profile lists the other in its co-administration data.
What is the FDA status of FOXO4-DRI and NAD+?
FOXO4-DRI: Not approved (research only). NAD+: Not approved (IV off-label). FDA-status text is pulled verbatim from each compound profile. See /fda-pcac-2026.html for the broader FDA Pharmacy Compounding Advisory Committee context.
Where can I find the full research on FOXO4-DRI and NAD+?
Full citation lists, dosing tables from the literature, reconstitution data, and the FDA / WADA status are on the individual compound profiles: the FOXO4-DRI profile and the NAD+ profile. The Kalios Stack Research Tool hub lists every compound covered.
Last updated: April 2026