Aging & Longevity

Changes in β-amyloid (Aβ) and hyperphosphorylated tau (T) in brain and cerebrospinal fluid (CSF) precede Alzheimer's disease (AD) symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies. Using the AT framework and a three-stage study design (discovery, replication, and meta-analysis), we identified 2,173 analytes (2,029 unique proteins) dysregulated in AD. Of these, 865 (43%) were previously reported, and 1,164...

The liver is a metabolic powerhouse, crucial for regulating carbohydrates, fats, and protein metabolism. In this study, we conducted a comparative proteomic and phosphoproteomic analysis of aging mouse livers from young adults (3-4 months) and old (19-21 months) mice to identify age-related changes in liver proteins and phosphosites, which were linked to various metabolic pathways. In old mice, proteins associated with the "complement and coagulation cascade," "age-rage signaling in diabetic...

The initial setting of telomere length during early life in each individual has a major influence on lifetime risk of aging-associated diseases; however there is limited knowledge of biological signals that regulate inheritance of telomere length, and whether it is modifiable is not known. We now show that when mitochondrial activity is disrupted in mouse zygotes, via exposure to 20% O(2) or rotenone, telomere elongation between the 8-cell and blastocyst stage is impaired, with shorter telomeres...

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Ageing-induced skeletal muscle deterioration contributes to sarcopenia and frailty, adversely impacting the quality of life in the elderly. However, the molecular mechanisms behind primate skeletal muscle ageing remain largely unexplored. Here, we show that SIRT5 expression is reduced in aged primate skeletal muscles from both genders. SIRT5 deficiency in human myotubes hastens cellular senescence and intensifies inflammation. Mechanistically, we demonstrate that TBK1 is a natural substrate for...

Social disadvantage, like advanced age, is a risk factor for a broad range of health conditions; however, whether it influences the aging process remains unclear. Here, using a multicohort approach, we investigated the associations of social disadvantage with age-related plasma proteins and age-related diseases. We found proteomic signatures of accelerated immune aging and 14 specific age-related proteins linked to social disadvantage during both early and later life. Individuals experiencing...

CONCLUSIONS: The prevalence of frailty among older adults with comorbidities is exceptionally high, influenced by various dimensions from health ecology perspective. Psychological care and daily behavior management should be strengthened for the frail older with multimorbidity. Precise and individualized care interventions need to be developed to help promote healthy aging.

CONCLUSION: The current investigation unveiled that PNI has emerged as an autonomous determinant for both short-and long-term mortality in older adults receiving CABG.

CONCLUSIONS: All VI measures predicted faster declines in SPPB. Older adults with VI may benefit from targeted intervention to prevent declines in mobility.

CONCLUSIONS: Despite inadequate knowledge and limited experience in frailty management, clinical nurses' attitudes towards frailty management were positive, indicating potential for improvement. The model was useful to explain practices in frailty management, thereby providing a theoretical basis for development of targeted training programs.

Geroscience has helped to usher in a new and exciting era of aging drug development and evaluation of novel and repurposed agents, as well as natural compounds purported to target one or more aging hallmarks. Among the latter, curcumin has long been pursued as a promising strategy but has failed to provide convincing evidence in human trials. Oral intake is the typical route of administration tested for the vast majority of gerotherapeutic candidates, including curcumin, but efficacy is...

Europe is experiencing a significant demographic shift, with aging populations posing economic and social challenges due to increased healthcare costs and a higher prevalence of age-related diseases. Hungary, in particular, faces these challenges acutely due to higher morbidity and mortality rates from a range of chronic age-related diseases and behavioral risk factors. Addressing these issues requires innovative approaches to promote healthy aging. Semmelweis University, the largest healthcare...

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We leverage a clinical trial (NCT04080804) that compared neoadjuvant anti-PD-1, anti-PD-1+CTLA-4, and anti-PD-1+LAG-3 therapies in head and neck squamous cell carcinoma patients. Combination therapies promote higher pathologic response rates versus monotherapy, and major pathologic response is associated with better survival. To address whether successful immune checkpoint inhibitor (ICI) regimens act through similar or distinct pathways, we robustly and longitudinally characterize...

White-matter diseases like multiple sclerosis begin in young adulthood. Aging, being a risk factor, contributes to the progression of these diseases and makes neurological disabilities worsen. Aging causes white matter alteration due to myelin loss, axonal degeneration, and hyperintensities, resulting in cognitive impairment and neurological disorders. Aging also negatively affects central nervous system resident glial cells and peripheral immune cells, contributing to myelin degeneration and...

Neuroinflammaging is the nervous system version of inflammaging, the low-grade inflammation that develops with advanced age, aside from active disease or infection. Despite neuroinflammaging has been widely investigated, some important issues still need to be resolved such as the analysis of the extremely old subjects and the evaluation of specific brain areas. On this background, we conducted a study to analyze expression of inflammatory and anti-inflammatory genes in Wistar rats of different...

The orexinergic system is anatomically and functionally conserved in almost all vertebrates, and the role in healthy ageing and age-associated diseases has been studied in mammals. Here, we review the main findings on the age-related regulation of orexinergic system in mammals, including human patients and highlights how the fish Nothobranchius furzeri serves as an exceptional model to spearhead research and unravel the intricate mechanisms underlying orexinergic regulation during ageing. The...

To check whether the reported waves of age-dependent changes in multiomics patterns in humans influence age-specific mortality, life-table aging rate (LAR) trajectories derived from Human Morality Database (HMD) data were modeled based on assumptions inherent in a generalized Gompertz-Makeham Law (gGML). The gGML implies that any changes in resistance to causes of death (CoD) and in exposure to CoD are translated into changes in mortality in an exponential and a linear way, respectively....