Plant Monoterpenes and Essential Oils as Potential Anti-Ageing Agents: Insights from Preclinical Data

**Background:** The global population aged 60 years or older is projected to reach 2.1 billion by 2050, driving interest in interventions that promote healthy ageing. Ageing involves 12 hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, compromised autophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. Natural compounds, particularly monoterpenes—volatile compounds abundant in aromatic plants—have attracted attention due to their antioxidant, anti-inflammatory, and antimicrobial properties. Many monoterpenes are generally recognized as safe (GRAS) by the FDA. This narrative review provides an up-to-date overview of the effects of monoterpenes and essential oils on the hallmarks of ageing, identifies mechanisms of action, and highlights knowledge gaps.

**Methods:** The authors conducted a literature search in PubMed combining the term "monoterpene" with each hallmark of ageing, without date restrictions. For inflammation, a more targeted search was performed due to the high volume of studies (>1500). Studies were included if they reported effects of volatile monoterpenes or essential oils on ageing hallmarks in vitro or in vivo. The review is narrative and does not follow a systematic review protocol; no meta-analysis was performed.

**Key Results:** - **Genomic Instability:** Only two in vitro studies were identified. α-Pinene (25–50 µM) in Chinese hamster V79-Cl3 cells increased apoptotic cells, multipolar spindles, hypodiploid metaphases, chromosome breaks, kinetochore-negative micronuclei, DNA lesions, and ROS production. D-Limonene (2–2.5 mM) in V79 cells increased nuclear abnormalities, aberrant spindles, and cytokinesis failure. In contrast, *Thymus vulgaris* essential oil (0.2% w/w) in aged C57BL/6J mice increased survival and significantly lengthened blood telomeres. - **Mitochondrial Dysfunction:** Multiple monoterpenes showed beneficial effects. For example, 1,8-cineole (400 µg/mL) in H9c2 cardiomyoblasts reduced mitophagy and mitochondrial fission and restored complexes III and V. Carvacrol (100 µM) in SH-SY5Y neuroblastoma cells increased complexes I and V activities, ATP levels, and mitochondrial membrane potential. Geraniol (60 nM) in SK-N-SH cells reduced ROS, increased mitochondrial membrane potential, complex I activity, and ATP production. In vivo, carvacrol (30 and 60 mg/kg p.o.) in a neuropathic pain rat model increased ATP production and NRF-1, TFAM, PGC-1α, complex I, and ATP synthase C protein levels while decreasing Drp1 and Fis1. - **Cellular Senescence:** Five monoterpenes were studied. α-Pinene (30 µM) in HaCaT keratinocytes reduced single-strand DNA damage and pyrimidine dimers, increased NER pathway proteins, and upregulated p53 and p21. D-Limonene (25–100 µM) decreased α-MSH, POMC mRNA, and phosphorylated p53. Myrcene (0.1–10 μM) in dermal fibroblasts reduced ROS, MMP-1, MMP-3, and IL-6 secretion, and increased procollagen-1 and TGF-1β. In vivo, camphor (26 and 52 mM topical) in UV-irradiated mice increased collagen I, II, and elastin, and decreased MMP-1. - **Autophagy:** Effects were context-dependent. Carvacrol (2.5–10 µg/mL) in H9c2 cells increased Beclin-1 and decreased p62. 1,8-Cineole (20 µM) in grass carp hepatocytes increased LC3B fluorescence and decreased p62. In contrast, 1,8-cineole (5–50 µM) in HUVEC cells decreased LC3-II/LC3-I ratio and increased p62. In vivo, borneol (0.16 mg/kg/day p.o.) in cerebral ischemia/reperfusion rats increased ULK1 and LC3-II/LC3-I ratio in cortex and hippocampus. - **Inflammation:** This was the most studied hallmark. Carvacrol (10 mg/kg) in HUVEC cells decreased IKK, NALP3, NF-κB, and TLR4 mRNA and protein. 1,8-Cineole (6.25–200 µM) in BEAS-2B cells increased Nrf2 nuclear translocation and decreased ROS and IL-6. Geraniol (200–1000-fold concentrations) in BV-2 microglial cells decreased TNF-α and IL-6 mRNA and secretion. In vivo, carvacrol (50 mg/kg intranasal) in FM1-infected mice increased Treg cells and decreased Th1/Th2 and Th17/Treg ratios. Menthol (10 and 20 mg/kg gavage) in LPS-induced Parkinson's disease rats decreased Iba-1-positive cells, iNOS, COX-2, IL-1β, IL-6, and TNF-α. - **Dysbiosis:** Only one study was identified. Geraniol (30 and 120 mg/kg p.o. or enema) in DSS-induced colitis mice maintained microbiota composition similar to healthy mice, increased Bacteriodetes and Lactobacillaceae populations.

**Clinical Implications:** Monoterpenes and essential oils show promise as anti-ageing agents by targeting multiple hallmarks, particularly inflammation, mitochondrial dysfunction, and autophagy. However, the majority of studies are preclinical, often in cancer or disease models rather than ageing contexts. Clinical translation is hindered by volatility, low water solubility, and limited pharmacokinetic data. Encapsulation strategies may improve bioavailability. The review emphasizes the need for more studies on under-researched hallmarks (epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, stem cell exhaustion, altered intercellular communication) and for well-controlled human trials to validate efficacy and safety in ageing populations.