👤 Sergey Mitrofanov

Most genomic studies compare the genomes of long-living adults to those of the general population to identify potential genetic markers of longevity. We propose a refined approach: focusing on the genetic makeup of healthy, long-living adults to detect mechanisms promoting both longer lifespan and improved quality of life. To this end, we analyzed medical and genomic data from 3,703 long-living adults aged ≥90 years and 22,354 individuals aged 18-75 years (total N = 26,057). Using whole-genome sequencing (WGS) and a genome-wide association study (GWAS), we found that variants with significant and negative associations with longevity in the GWAS were located in genes such as APOE, APOC1, and CFAP46, which are implicated in an increased risk of age-related diseases. However, the presence or absence of these variants should not be considered a definitive determinant of longevity or sustained health after the age of 90. We found that healthy longevity was positively associated with variants within the MYO18B, TBC1D28, and LOC105376454 genes. To demonstrate the multifactorial nature of the examined phenotypes, we constructed polygenic score models that accounted for nonlinear interactions among the predictors. Trial registration: Clinical Trials NCT06268132 (for long-living adults). Registered 22 February 2024 (retrospectively registered). Show less

Long-living adults often maintain cognitive function despite neuropathological changes, which is often attributed to cognitive resilience (CR)-a combined effect of cognitive and cerebral reserves. CR is influenced by genetic, clinical, sociodemographic, and environmental factors. We investigated genetic, clinical, and environmental predictors of CR in 198 dementia-free long-living adults via two neuropsychological examinations over a 2-year period, a geriatric assessment, and a genome-wide association study (GWAS). Limited mobility, reduced walking, hearing impairment, depression, anemia, lower quality of life, and decreased BMI were key accelerators of CI. Depression, hypercholesterolemia, and lack of hobbies increased the risk of mild cognitive impairment (MCI)-to-dementia progression. GWAS identified CR-associated genetic variants, including a missense mutation in Our findings corroborated established risk factors for cardiovascular diseases and identified population-specific patterns, with APOE ε4 showing no significant association. Both protein-coding regions and non-coding elements were implicated in CI, suggesting that it is underlain by complex regulatory mechanisms. Show less

Long-persistent luminescent (LPL) materials store photon energy as charges and emit light over extended periods via charge recombination. LPL decay typically follows a power law rather than an exponential decay, enabling confirmation of charge accumulation from emission decay characteristics. While charge generation in organic materials has been widely studied at donor-acceptor (D/A) interfaces, it remains underexplored in single-component luminescent materials. Here, we investigate charge generation in organic solids by dispersing a luminescent molecule in various hosts and performing slow transient emission analyses. This approach enables the evaluation of ionization through accumulated triplet excited states and the detection of weak charge accumulation, which are difficult to capture using conventional transient techniques. Our results show that ionization in single-component materials proceeds through resonance-enhanced multiphoton ionization, although it is less efficient than at D/A interfaces. This approach provides insight into long-term photophysical and photochemical processes such as photodegradation. Show less

Long-persistent luminescence (LPL) materials have applications from safety signage to bioimaging; however, existing organic LPL (OLPL) systems do not align with human scotopic vision, which is sensitive to blue light. We present a strategy to blueshift the emissions in binary OLPL systems by upconverting the charge-transfer (CT) to a locally excited (LE) singlet state. Through rigorous steady-state and time-resolved photoluminescence spectroscopy and wavelength-resolved thermoluminescence measurements, we provide the direct experimental evidence for this upconversion in OLPL systems featuring small energy offsets between the lowest-energy CT and LE singlet states. These systems exhibited strong room temperature LPL, particularly when extrinsic electron traps are added. Importantly, the developed OLPL system achieved Class A (ISO 17398) LPL, matching well with human scotopic vision. The findings not only elucidate the role of small energy offsets in modulating LPL but also provide potential avenues for enhancing the efficiency and applicability of OLPL materials. Show less