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The coenzyme NAD^(+) is consumed by signalling enzymes, including poly-ADP-ribosyltransferases (PARPs) and sirtuins. Ageing is associated with a decrease in cellular NAD^(+) levels, but how cells cope with persistently decreased NAD^(+) concentrations is unclear. Here, we show that subcellular NAD^(+) pools are interconnected, with mitochondria acting as a rheostat to maintain NAD^(+) levels upon excessive consumption. To evoke chronic, compartment-specific overconsumption of NAD^(+), we...

Extracellular vesicles (EVs) offer valuable diagnostic and prognostic insights for cardiovascular (CV) diseases, but the influence of age-related chronic inflammation ("inflammaging") and sex differences on EV profiles linked to CV risk remains unclear. This study aimed to use EV profiling to predict age and stratify patients by CV risk. We developed an EVaging index by analyzing surface antigen profiles of serum EVs from 625 participants, aged 20 to 94 years, across varying CV risk groups. The...

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The development of anti-aging drugs is challenged by both the apparent complexity of the physiological mechanisms involved in aging and the likelihood that many of these mechanisms remain unknown. As a consequence, the development of anti-aging compounds based on the rational targeting of specific pathways has fallen short of the goal. To date, the most impressive compound is rapamycin, a natural bacterial product initially identified as an antifungal, and only subsequently discovered to have...

Cell death and related signaling pathways are essential during development and in various physiological and pathological conditions. Post-translational modifications such as ubiquitination and phosphorylation play an important role in these signaling pathways. The involvement of kinases - enzymes that catalyze protein phosphorylation - in cell death signaling has been extensively studied. On the other hand, not many studies have been devoted to analyzing the role in cell death of phosphatases,...

To understand how the health of older adults today compares to that of previous generations, we estimated intrinsic capacity and subdomains of cognitive, locomotor, sensory, psychological and vitality capacities in participants of the English Longitudinal Study of Ageing and the China Health and Retirement Longitudinal Study. Applying multilevel growth curve models, we found that more recent cohorts entered older ages with higher levels of capacity, while subsequent age-related declines were...

Uncouplers of mitochondrial electron transport chain, such as 2,4-dinitrophehol (DNP), can mimic calorie restriction by decreasing efficiency of adenosine triphosphate (ATP) synthesis. However, DNP is also a toxic substance, whose overdosage can be lethal. In the fruit fly, Drosophila melanogaster model, we have found that DNP in concentrations of 0.05-0.2 g/L, led to a drastic decrease in fruit fly survival on a low caloric diet (1% sucrose and 1% yeast; 1S-1Y). On the 5S-5Y diet, DNP decreased...

Advanced Glycation End (AGE) products are one such factor that accumulates during aging and age-related diseases. However, how exogenous AGE compounds cause aging is an area that needs to be explored. Specifically, how an organ undergoes aging and aging-related phenomena that need further investigation. The intestine is the most exposed area to food substances. How AGEs affect the intestine in terms of aging need to be explored. Drosophila melanogaster, a well-known model organism, is used to...

OBJECTIVES: This study examines whether social engagement at the time of retirement is associated with better cognitive function and slower cognitive decline.

INTRODUCTION: We investigated the neural correlates of cognitive decline in visual word perception from the perspective of intrinsic brain networks.

INTRODUCTION: Previous research has tended to focus on early-life education for dementia risk reduction, yet there are great gains for building cognitive reserve in mid- to later-life through educational interventions. ISLAND (Island Study Linking Ageing and Neurodegenerative Disease) Campus offered free university study to all ISLAND participants, with flexible in-person/online learning models to remove educational, socioeconomic and geographical barriers. Here the core hypothesis of ISLAND...

Storms may be confounding measurements at high-altitude observatories of the universe’s highest energy light