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The aggregation of α-synuclein into amyloid fibrils is a hallmark of Parkinson's disease. This process has been shown to directly involve interactions between proteins and lipid surfaces when the latter are present. Despite this importance, the molecular mechanisms of lipid-induced amyloid aggregation have remained largely elusive. Here, we present a global kinetic model to describe lipid-induced amyloid aggregation of α-synuclein. Using this framework, we find that α-synuclein fibrils form via...

By predicting the effects of genetic variants, AlphaGenome could boost synthetic biology and the search for cancer genes

ObjectivesThis study examines whether social strain and support from various sources are associated with accumulation of chronic conditions in older adults.MethodsGrowth mixture modeling was used to investigate which network sources of support and strain were related to morbidity accumulation over 12 years among 5,321 individuals over age 50 in the Health and Retirement Study.ResultsHigher overall social support-comfort provided by others-was associated with a greater likelihood of belonging to...

Exacerbating the DNA replication problems of cancer cells serves as a viable therapeutic approach. Nevertheless, the cytotoxicity of cancer drugs is often hampered by therapy-induced senescence, leading to unfavorable patient outcomes. Here, we employ acute replisome dysfunction in combination with Ataxia telangiectasia and Rad3-related (ATR) inhibition as a strategy to divert senescent cells toward death by triggering DNA replication catastrophe, a form of irreversible replication fork collapse...

Neurons maintain their morphology over prolonged periods of adult life with limited regenerative capacity. Among the various factors that shape neuronal morphology, lipids function as membrane components, signaling molecules, and regulators of synaptic plasticity. Here, we tested genes involved in phospholipid biosynthesis and identified their roles in axon regrowth and maintenance. CEPT-2 and EPT-1 are enzymes catalyzing the final steps in the de novo phospholipid synthesis (Kennedy) pathway....

SCOPE: Cardiovascular disease (CVD) is a major cause of mortality, especially in the aging population. Aging is one of the main risk factors contributing to CVD, leading to early mortality and a decline in the quality of life. Vascular aging is closely linked with atherosclerosis, diabetes, hypertension, stroke, heart failure, and peripheral arterial diseases. Elucidating the cellular and molecular mechanisms underlying vascular aging help to develop therapeutic strategies that can address...

Biological aging is a complex non-linear process, with markedly distinct starting and end points, yet the biomarkers of its progression remain elusive. A key assumption of most machine learning (ML) approaches for age clocks is that predictive biomedical features can be identified via mathematical transformations of data to favor a linear transition from start to end, even if they erase any natural biological pattern. It is given that expected correlations, e.g., time lived (age) and time left...

Aging is an unavoidable process associated with a progressive decline of muscle mass, strength, and regenerative ability. Satellite cells are a muscle stem cell (MuSC) population that plays a key role in mammalian muscle regeneration, by awakening from quiescence and then migrating to sites of damage, expanding in number to generate progenitor cells, and then either differentiating to rebuild the muscle tissue or self-renewing to repopulate the stem cell pool. Emerging evidence suggests that the...

Antiaging vaccines have recently been found to elicit long-term benefits in slowing the aging process. Meanwhile, high CD38 expression in organs is an aging characteristic contributing to a decreased NAD^(+)/NADH ratio. Thus, in the current study, we systematically investigate the effects of a CD38-targeting peptide vaccine (CD38-vaccine) on aging-associated phenotypes in mice. The CD38-vaccine induces a robust T-cell immune response, selectively depletes CD38^(+) myeloid cells in the spleen,...