The Biology of Aging: A Research Literature Overview

What the published research examines across SS-31 (elamipretide), NAD+ and its precursors, and Epithalon (AEDG) — three compounds mapping onto mitochondrial, NAD+, and pineal-peptide research themes.

Aging-biology research focuses on interlocking cellular mechanisms: declining mitochondrial bioenergetics, age-associated NAD+ depletion, and changes in telomere and neuroendocrine (pineal) signaling. The three compounds here map onto those themes. Their clinical evidence differs markedly: elamipretide and NAD+ precursors have peer-reviewed human trials, while published human data for Epithalon remain limited and largely concentrated in a small number of research groups.

SS-31 (elamipretide)

Class / mechanism. A synthetic aromatic-cationic tetrapeptide that concentrates in the inner mitochondrial membrane and associates with cardiolipin; studied for effects on membrane stabilization and mitochondrial bioenergetics.

Elamipretide has been evaluated in preclinical models and in human trials, most prominently in primary mitochondrial myopathy (PMM) and Barth syndrome. Clinical development is comparatively advanced for this class; a registrational program was conducted in Barth syndrome, while the pivotal PMM trial did not meet its primary endpoints. Much of the mechanistic literature remains preclinical.

Selected literature

1. Karaa A, et al. 2023. “Efficacy and safety of elamipretide in primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial.” Neurology. PMID 37268435. https://pubmed.ncbi.nlm.nih.gov/37268435/Phase-3 RCT on six-minute walk distance and fatigue; did not meet primary endpoints.
2. Karaa A, et al. 2018. “Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy.” Neurology. PMID 29500292. https://pubmed.ncbi.nlm.nih.gov/29500292/Earlier randomized dose-escalation study of tolerability and exercise measures.
3. Reid Thompson W, et al. 2021. “A phase 2/3 trial of elamipretide in Barth syndrome.” Genet Med. https://www.nature.com/articles/s41436-020-01006-8Controlled trial (TAZPOWER) of functional/cardiac endpoints with open-label extension.
4. Pharaoh G, et al. 2023. “Elamipretide (SS-31) improves ADP sensitivity in aged mitochondria.” GeroScience. PMID 37462785. https://pubmed.ncbi.nlm.nih.gov/37462785/Preclinical mechanistic study of ADP sensitivity in aged skeletal-muscle mitochondria.

NAD+ (with NR / NMN precursor context)

Class / mechanism. An essential redox coenzyme and substrate for enzymes including sirtuins, PARPs, and CD38. Research describes an age-associated decline in tissue NAD+ and studies whether oral precursors (NR, NMN) can raise NAD+ and influence downstream pathways.

NAD+ biology is supported by extensive preclinical literature and a growing set of human trials, most using NR or NMN rather than NAD+ itself. Human studies have generally focused on pharmacokinetics, tolerability, and biomarker changes (blood NAD+ elevation); clinical outcome data in aging and disease remain preliminary and mixed.

Selected literature

1. Verdin E. 2015. “NAD+ in aging, metabolism, and neurodegeneration.” Science 350(6265):1208–1213. PMID 26785480. https://pubmed.ncbi.nlm.nih.gov/26785480/Review framing NAD+ decline in aging, metabolism, and neurodegeneration.
2. Trammell SAJ, et al. 2016. “Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.” Nat Commun 7:12948. https://www.nature.com/articles/ncomms12948First-in-human PK study reporting oral NR raises blood NAD+ metabolites.
3. Martens CR, et al. 2018. “Chronic NR supplementation is well tolerated and elevates NAD+ in middle-aged and older adults.” Nat Commun 9:1286. https://www.nature.com/articles/s41467-018-03421-7Randomized placebo-controlled crossover trial of tolerability and NAD+ elevation.
4. Brakedal B, et al. 2022. “The NADPARK study: a randomized phase I trial of NR in Parkinson’s disease.” Cell Metab 34(3):396–407. PMID 35235774. https://pubmed.ncbi.nlm.nih.gov/35235774/Randomized phase-I trial of NR on cerebral/blood NAD+ and clinical measures.

Epithalon (AEDG)

Class / mechanism. A synthetic tetrapeptide (Ala-Glu-Asp-Gly) designed as a short-peptide analog of the pineal peptide preparation Epithalamin. Research investigates proposed effects on telomerase expression and pineal-melatonin signaling.

The published Epithalon literature is comparatively limited and drawn substantially from a small number of research groups in Russia (notably associated with Khavinson and colleagues). It includes in-vitro work, rodent lifespan/tumor-incidence studies, and human/clinical reports — several of which involve the related preparation Epithalamin rather than the synthetic AEDG tetrapeptide itself.

Selected literature

1. Khavinson VKh, et al. 2003. “Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells.” Bull Exp Biol Med 135(6):590–592. PMID 12937682. https://pubmed.ncbi.nlm.nih.gov/12937682/In-vitro study of telomerase activity in cultured human fibroblasts.
2. Anisimov VN, et al. 2003. “Effect of Epitalon on biomarkers of aging, life span and tumor incidence in mice.” Biogerontology 4(4):193–202. PMID 14501183. https://pubmed.ncbi.nlm.nih.gov/14501183/Rodent study of aging biomarkers, lifespan parameters, and tumor incidence.
3. Korkushko OV, et al. 2011. “Peptide geroprotector from the pineal gland: results of 15-year follow-up.” Bull Exp Biol Med 151(3):366–369. PMID 22451889. https://pubmed.ncbi.nlm.nih.gov/22451889/Long-term follow-up report of a pineal peptide preparation in an elderly cohort.

How to read this report

This report aggregates published scientific literature for the compounds NOVA Q Research supplies in the Longevity category. It describes what studies investigated, the models used, and the maturity of the evidence. It does not evaluate, recommend, or imply any use in humans or animals, and it is not medical, veterinary, or research-protocol advice. Where the record is preclinical or geographically concentrated, we say so. Every source is cited so it can be checked independently.