Human ageing and longevity are increasingly understood as biologically integrated and heterogeneous processes shaped by interactions among genetic susceptibility, epigenetic remodelling, and environmental modulation. This narrative review examines these interconnections within a nutrigenomic framework, with particular emphasis on how inherited variation and epigenetic plasticity may influence responses to ageing-related interventions. A structured literature search was conducted in PubMed, Scopus, Web of Science, and Embase, focusing on English-language studies published during the last 10 years. The review was organized into three major domains: (i) genetic determinants of longevity, (ii) epigenetic mechanisms of ageing, and (iii) intervention-responsive pathways relevant to precision geroscience. Current evidence supports a polygenic model of longevity in which loci such as FOXO3 and APOE show the most consistent human associations, while telomere maintenance, insulin/IGF-1 and mTOR signalling, sirtuins, Klotho, inflammatory mediators, and DNA repair remain biologically important but variably supported at the variant level. Epigenetic mechanisms, including DNA methylation drift, epigenetic clocks, histone modifications, chromatin remodelling, heterochromatin loss, and non-coding RNA regulation, provide an environmentally responsive interface linking genetic background to ageing phenotypes. Nutritional, pharmacological, behavioural, and circadian interventions converge on overlapping molecular pathways involving AMPK, mTOR, FOXO, sirtuins, autophagy, mitochondrial maintenance, and inflammatory signalling, although human evidence remains heterogeneous and biomarker modulation should not be equated with clinically meaningful slowing of organismal ageing. Overall, this review highlights the value of integrating genetics, epigenetics, and intervention biology to support a more cautious and translationally relevant model of healthy ageing. It also underscores the need for precision nutrigeroscience approaches that account for tissue context, baseline physiology, and inter-individual molecular variability.

Background: Triple primary malignant tumors (TPMTs) are extremely rare and represent a major diagnostic and therapeutic challenge. Their frequency has increased with advances in cancer detection and longer patient survival. Case presentation: We report the case of a 76-year-old male diagnosed with three synchronous primary malignancies involving the liver, left kidney, and right lung. Imaging revealed a hepatic mass with arterial enhancement and portal washout, a large left renal mass, and a cavitated pulmonary nodule. Histopathological and immunohistochemical evaluation confirmed three distinct tumors: well-differentiated hepatocellular carcinoma, chromophobe renal cell carcinoma, and invasive non-mucinous lung adenocarcinoma. A multidisciplinary oncology board recommended surgical resection of the liver and kidney lesions and stereotactic body radiotherapy for the lung tumor. The patient underwent hepatectomy and nephrectomy but experienced severe postoperative complications leading to multi-organ failure and death. Results of the systematic review: A systematic search identified 83 relevant cases of triple primary malignancies after full-text eligibility assessment. None of the 159 articles included after primary screening described a synchronous association of primary liver, kidney, and lung cancers. Conclusions: This case highlights the importance of thorough diagnostic assessment and individualized, multidisciplinary management in patients with multiple synchronous malignancies. To our knowledge, this is the first reported case of synchronous hepatocellular carcinoma, chromophobe renal cell carcinoma, and lung adenocarcinoma.

Resistance to apoptosis, metabolic plasticity, and redox adaptation are major contributors to cancer progression and treatment failure. Ferroptosis and cuproptosis have therefore emerged as metal-dependent forms of regulated cell-death programs with potential relevance for tumours that survive conventional therapy. Ferroptosis is driven by iron-dependent phospholipid peroxidation when glutathione peroxidase 4 (GPX4)-dependent and parallel antioxidant systems fail, whereas cuproptosis depends on mitochondrial copper engagement of lipoylated tricarboxylic-acid-cycle proteins, lipoylated-protein aggregation, iron–sulfur protein destabilization, and proteotoxic stress. This review integrates the molecular basis, genetic architecture, long non-coding RNA (lncRNA)-mediated regulation, mechanistic crosstalk, and therapeutic implications of ferroptosis and cuproptosis in cancer. It emphasizes a critical evidence hierarchy: expression association, computational signature construction, metal accumulation, reactive oxygen species (ROS) generation, or reduced viability should not be interpreted as pathway dependency without pathway-defining biochemical endpoints and rescue experiments. The most credible translational opportunities will depend on functional stratification, tumour-selective delivery, and pharmacodynamic confirmation that distinguishes pathway-defined ferroptosis or cuproptosis from nonspecific metal-induced and oxidative cytotoxicity.

Somatic blood mosaicism is an established feature of ageing and a heterogeneous marker of haematologic cancer and inflammatory and vascular risk, but its psychiatric evidence base remains small. This structured critical narrative review evaluates mutation-defined clonal haematopoiesis, clonal haematopoiesis of indeterminate potential (CHIP), autosomal mosaic chromosomal alterations (mCAs), and sex-chromosome loss while separating probable developmental mosaicism from adult-acquired blood clonality. Direct human evidence comprises seven methodologically heterogeneous studies. Psychiatric CHIP findings rely mainly on one prospective UK Biobank cohort of 360,451 participants, in which CHIP was associated with any incident psychiatric disorder (hazard ratio 1.15), particularly major depressive and substance-use disorders. Separate studies report excess mosaic losses in schizophrenia and bipolar disorder and autosomal or X-chromosome mosaicism in suicide. Clone-size gradients and lesion-specific findings add biological structure, but do not provide independent replication. Most mechanistic support comes from cardiovascular, stroke and neurodegenerative research: mutant myeloid cells can alter inflammasome signalling, endothelial function, thrombosis and tissue macrophage behaviour. These pathways make indirect brain effects plausible without establishing a psychiatric mechanism. Blood detection also cannot date a mosaic event or demonstrate the same clone in neural tissue. Taken together, the available evidence supports somatic blood mosaicism as a potentially informative marker of psychiatric heterogeneity and shared inflammatory, vascular and ageing-related biology, but does not establish a causal blood-clone-to-brain pathway. Routine psychiatric screening for CHIP or mCAs is therefore not currently justified. The immediate research priority is independent replication in longitudinal cohorts with repeated sequencing, detailed exposure and treatment histories, and direct testing of inflammatory, vascular and neuroimaging intermediates capable of distinguishing cause, consequence and shared risk.