Creative solutions are needed to combat increasing rates of metabolic disease and promote healthy aging. This review summarizes the latest research on protein and branched-chain amino acid restriction as interventions to alter metabolism to extend lifespan and reduce frailty in model organisms and humans. The authors discuss the potential mechanisms underpinning these dietary interventions and postulate future directions of the field, which may include personalized nutrition therapy.

With age, there is a decline in sleep quality and cognitive ability that is associated with increased ER stress, which results in PERK activation and attenuated protein translation. Systemic administration of small molecule chaperone, PBA, improves sleep and cognition in aged mice by reducing PERK activation and GADD34, that is correlated with increased levels of p-CREB. Local hippocampal overexpression of endogenous chaperone, BiP, is sufficient to reduce PERK activation, restore CREB activity and improve cognition.

DNA methylation (DNAm) is an important epigenetic regulatory mechanism and is associated with many diseases and with human aging. Our study demonstrated that inter-individual variation in DNAm is associated with all-cause mortality risk and with cause-specific mortality. We built a prediction model by integrating DNAm with clinical risk factors and we show that doing so can improve mortality prediction.

Our findings show that CMA is activated under oxidative condition, resulting in the degradation of Keap1 and activation of Nrf2. This protects cells against oxidative stress. Moreover, Nrf2 increases the transcription of LAMP2A gene, which in turn further activates CMA. We provide a novel mechanism by which CMA-Nrf2 forms a positive feedback loop to augment antioxidative response and protect cells from oxidative stress.

Alzheimer's disease (AD) is the most common form of dementia with a high genetic influence. A previous study identified a rare variant (rs144662445) in AKAP9 (a kinase anchor protein 9) conferred a high risk for AD in African American population, suggesting a pathogenic role of AKAP9 mutation. By using CRISPR-edited human neuronal cells, this study revealed specific effects of rs14462445 on mis-processing of tau and recapitulation of phenotypes observed in AD, including dysregulation of protein synthesis and excessive oxidative stress.

Menopause is associated with increases in total and regional body adiposity, with a pronounced increase in the android area. Adipose tissue-derived adipokines, adiponectin, leptin and resistin, were uniquely associated with menopausal transition. Lifestyle habits, such as higher diet quality and physical activity level, but not external hormone use, were associated with lower adiposity in several body regions.

Metabolic, oxidative stress and drug toxicity induced stress causes macrophage mitochondrial damage to promote cytosolic mtDNA release and STING activation. Mitophagy serves as an important negative feedback regulatory mechanism to mediate STING activation by degrading damaged mitochondia. Aging impairs mitophagy activation by inhibiting PINK1-mediated mitochondrial ubiquitination and lysosome biogenesis and function.

Age-associated thymus involution impairs the capacity of the middle-aged thymus to support central tolerance to self-antigens with moderate TCR avidities, although tolerance to high avidity self-antigens remains intact. The decline in both negative selection and generation of regulatory T cells by middle-age is associated with reduced numbers and proportions of AIRE⁺ mTECs and MHCII^hi cDC1s.

WRN RECQ helicase, an anti-premature aging gene, acts as a critical regulator for removal of TOP1-DNA covalent complexes, ssDNA generation and activation of CHK1 signaling for NF-kB-mediated chemoresistance to TOP1 inhibitors.

Learning-activated MAPK signals are reported to protect labile memory in Drosophila. Such protective signals are gradually lost with age, making labile memory more vulnerable to interfering stimuli, which can lead to age-related memory impairment (AMI). Acutely restoring learning-activated MAPK signals in mushroom body neurons in aged flies significantly suppresses AMI even with interfering stimuli.

Continuous methionine restriction (MR) extends the healthspan of a number of model organisms, including rodents. Here, we show that 3 days of stringent MR per week (aka, intermittent MR; IMR) are sufficient to protect mice against diet-induced obesity, hepatosteatosis, and glucose intolerance, as well as confer additional metabolic health benefits. As a result, IMR may be a preferable alternative to continuous MR.

TNF-α and IFN-γ synergistically enhanced expression of SARS-CoV-2 viral entry receptors, amplified senescence-associated inflammation, and initiated a positive feedback loop via hyper-activation of the JAK/STAT1 pathway in endothelial cells. Inhibition of JAK/STAT with ruxolitinib or antiviral remdesivir normalised ACE2/DDP4 expression and controlled hyper-inflammation. Therapies with JAK inhibitors or drugs targeting JAK/STAT signaling could alleviate complications of cytokine storm in severe COVID-19 infection.

Aged mice have accumulated peripheral Treg cells (pTregs) with severe EAE symptoms. Treg distribution is disrupted outside and inside the inflamed CNS, combined with increased CNS-Treg plasticity. Transient inhibition of accumulated pTregs can redistribute Treg cells and mitigate the symptoms.

Promise of measuring a miRNA triad in the circulating blood as a biomarker of mild cognitive impairment (MCI) and Alzheimer's disease (AD), and the likely contribution of the miRNA triad to impaired neural plasticity and cognitive function in MCI and severe cognitive dysfunction in AD.