A plant-based diet, rich in phytochemicals, stands as a key to influencing longevity and fostering healthy aging. This is the objective of molecular biology, which aims to close the current gap between lifespan—the substantial extension of average life—and healthspan, the period of life lived free from chronic disease, a factor that significantly affects healthcare costs and the overall quality of life for individuals.
To achieve this, we must not only ensure survival but ensure a high-quality survival: a goal attainable through understanding the molecular processes that undermine cellular integrity and, consequently, by improving adaptive resilience.
A special issue of Pharmaceuticals highlights the role and potential of phytochemicals in modulating the biology of aging, thereby potentially influencing the onset of age-related diseases.
The Properties of Phytochemicals
Antioxidant capacity and the regulation of several biological processes—such as chronic low-grade inflammation, cellular senescence, mitochondrial dysfunction, and lipid metabolism—act as “triggers” of aging and the emergence of diseases, including serious ones. These are among the properties attributed to plants that can affect some of the main drivers of cellular senescence in a broad sense and specific functions tied more closely to lifespan.
A few examples of the potential effects exerted by plants and their phytochemicals:
Vascular Protection and Neuroinflammaging
A recent study conducted in ApoE knockout mice (ApoE−/−) shows that an infusion of white tea, rich in polyphenols, can improve plasma lipid profiles, reduce vascular inflammation and oxidative stress, and lower lesion burden, indicating in vivo models how a complex matrix of phytochemicals can remodel a multifactorial atherosclerotic phenotype.
These data support evidence from other studies suggesting that some algal carotenoids, particularly astaxanthin, may act as potential inhibitors of prostate protease subtilisin/kexin type 9 (PCSK9), a protease that drives degradation of hepatic LDL receptors and raises circulating LDL cholesterol. The results imply that rather than replacing current biological PCSK9 inhibitors, one might consider nutraceutical supplementation, particularly in individuals with moderate cardiovascular risk or in secondary prevention contexts where adherence to pharmacotherapy may be suboptimal.
Additional clinical and preclinical studies also point to astaxanthin’s ability to improve lipid profiles, enhance insulin sensitivity, and activate cytoprotective signaling via the phosphatidylinositol 3-kinase (PI3K)–AKT axis and the nuclear factor erythroid 2–related factor 2 (Nrf2), while simultaneously dampening nuclear factor κB (NF-κB) and systemic inflammation.
Of particular interest is the application of this class of dietary phytochemicals to the nervous system: some studies appear to highlight the influence of these molecules on the interaction between oxidative stress, neuroinflammation, and mitochondrial dysfunction in age-related neurodegenerative disorders. Notably, physcion, an anthraquinone found in many medicinal and plant-based sources, seems capable of dampening microglial activation and the release of proinflammatory cytokines in an lipopolysaccharide (LPS)-induced neuroinflammation model, upregulating Nrf2 and HO-1 and restoring synaptic proteins.
These data could offer new insights into the process of “neuroinflammaging,” the chronic, low-grade brain inflammation that accelerates cognitive decline. Other substances studied for potential anti-inflammatory or antimicrobial effects include apigenin and quercetin, two flavonoids abundant in propolis, and a standardized aqueous extract containing roots of Angelica gigas and flowers of Pueraria lobata, which reportedly improved immune function in macrophages and in immunodeficient mice. These findings support the existence of a gut–immune–brain axis and its relevance to aging and brain health.
Cellular Senescence
This represents a stress response triggered by DNA damage, telomere shortening, and mitochondrial dysfunction, among various possible stimuli, culminating in a stable arrest of the cell cycle. As a direct consequence, senescent cells lose their physiological function, become resistant to apoptosis, and release a senescence-associated proinflammatory secretory phenotype (SASP), driving tissue degeneration and chronic inflammation.
In this context, seno¬lytic phytochemicals are under observation as potential compounds capable of selectively eliminating senescent cells; among these of interest is ε-viniferin, a dimer of resveratrol, which appears able to reduce mitochondrial oxidative stress and rejuvenate senescent cells through regulation of the gene RGS16. Laboratory studies suggest this compound reduces mitochondrial reactive oxygen species (ROS) production, improves bioenergetic efficiency, and activates mitophagy, promoting the removal of damaged mitochondria.
Bone-Level Action
The loss of neuromuscular and metabolic integrity triggers sarcopenia and frailty, aging’s typical conditions, where phytochemicals may emerge as an effective countermeasure due to their mitochondrial-modulating properties, which also play a role in myogenesis and muscle regeneration.
For example, an extract from the shrub Cotoneaster microphyllus Nakai has been studied in experimental settings and shown to stimulate bone formation while reducing resorption, suggesting potential anti-osteoporotic effects. Meanwhile, other molecules such as resveratrol and sakuranetin have been observed to improve telomerase-related parameters, whereas apigenin, genistein, and esperetin allegedly exert significant anti-inflammatory effects: all factors, as noted, that contribute to the acceleration of aging.
The Expectations
Before phytochemicals can be integrated into clinical practice, research must address several unresolved aspects: their absorption and tissue distribution profiles, which remain a critical limitation for many phytochemicals and highlight the need for innovative delivery systems and a better understanding of microbiome-mediated metabolism; nonlinear dose–response relationships that remain poorly understood; and the development of studies with functional, patient-centered endpoints to determine whether promising preclinical results translate into measurable improvements in healthspan.
Source
Medoro A, Scapagnini G, Davinelli S. The Role of Phytochemicals in Aging and Aging-Related Diseases. Pharmaceuticals 2025, 18(11), 1713. Doi: https://doi.org/10.3390/ph18111713
Abbonati a Karla Miller
