Inhibitor PF-04691502 works as a senolytic to regulate cellular senescence.

Aging is a gradual process of natural change that occurs after reaching sexual maturity. It is also a known risk factor for many chronic diseases. Recent research has shown that senolytics can extend the lifespans and health spans of model organisms, and they have also been demonstrated effective in treating age-related diseases. In this study, we conducted a high-throughput screening of 156 drugs that targeted the PI3K/AKT/mTOR pathway to identify potential senolytic medications. Among these drugs, PF-04691502 was selected for further investigation to understand its molecular mechanism of action. Our findings indicate that PF-04691502, a dual inhibitor of PI3K/AKT and mTOR, specifically eliminates senescent cells. It reduces the expression levels of key markers of cellular senescence, such as SA-ß-Gal, senescence-associated secretory phenotypes (SASPs) and p16INK4a. Additionally, PF-04691502 inhibits the phosphorylation of S6K and AKT, leading to the apoptosis of senescent cells. These results suggest that PF-04691502 holds promise as a new senolytic drug. This paper provides important insights into the potential application of PF-04691502 in the study of cell senescence.

The adaptor protein 14-3-3zeta modulates intestinal immunity and aging in Drosophila.

The proteins that coordinate the complex transcriptional networks of aging have not been completely documented. Protein 14-3-3zeta is an adaptor protein that coordinates signaling and transcription factor networks, but its function in aging is not fully understood. Here, we showed that the protein expression of 14-3-3zeta gradually increased during aging. High levels of 14-3-3zeta led to shortened lifespan and imbalance of intestinal immune homeostasis in Drosophila, but the decrease in 14-3-3zeta protein levels by RNAi was able to significantly promote the longevity and intestinal immune homeostasis of fruit flies. Importantly, we demonstrate that adult-onset administration of TIC10, a compound that reduces the aging-related AKT and extracellular signal-regulated kinase (ERK) signaling pathways, rescues the shortened lifespan of 14-3-3zeta-overexpressing flies. This finding suggests that 14-3-3zeta plays a critical role in regulating the aging process. Our study elucidates the role of 14-3-3zeta in natural aging and provides the rationale for subsequent 14-3-3zeta-based antiaging research.

Flavonoids-Natural Gifts to Promote Health and Longevity.

The aging of mammals is accompanied by the progressive atrophy of tissues and organs and the accumulation of random damage to macromolecular DNA, protein, and lipids. Flavonoids have excellent antioxidant, anti-inflammatory, and neuroprotective effects. Recent studies have shown that flavonoids can delay aging and prolong a healthy lifespan by eliminating senescent cells, inhibiting senescence-related secretion phenotypes (SASPs), and maintaining metabolic homeostasis. However, only a few systematic studies have described flavonoids in clinical treatment for anti-aging, which needs to be explored further. This review first highlights the association between aging and macromolecular damage. Then, we discuss advances in the role of flavonoid molecules in prolonging the health span and lifespan of organisms. This study may provide crucial information for drug design and developmental and clinical applications based on flavonoids.

p62 works as a hub modulation in the ageing process.

p62 (also known as SQSTM1) is widely used as a predictor of autophagic flux, a process that allows the degradation of harmful and unnecessary components through lysosomes to maintain protein homeostasis in cells. p62 is also a stress-induced scaffold protein that resists oxidative stress. The multiple domains in its structure allow it to be connected with a variety of vital signalling pathways, autophagy and the ubiquitin proteasome system (UPS), allowing p62 to play important roles in cell proliferation, apoptosis and survival. Recent studies have shown that p62 is also directly or indirectly involved in the ageing process. In this review, we summarize in detail the process by which p62 regulates ageing from multiple ageing-related signs with the aim of providing new insight for the study of p62 in ageing.

Evaluation of passive sampling of gaseous mercury using different sorbing materials.

Atmospheric mercury monitoring is essential because of its potential human health and ecological impacts. Current automated monitoring systems include limitations such as high cost, complicated configuration, and electricity requirements. Passive samplers require no electric power and are more appropriate for screening applications and long-term monitoring. Sampling rate is a major factor to evaluate the performance of a passive sampler. In this study, laboratory experiments were carried out using an exposure chamber to search for high efficiency sorbents for gaseous mercury. Four types of sorbents, including sulfur-impregnated carbon (SIC), chlorine-impregnated carbon (CIC), bromine-impregnated carbon (BIC), and gold-coated sand (GCS) were evaluated under a wide range of meteorological parameters, including temperature, relative humidity, and wind speed. The results showed that the four sorbents all have a high sampling rate above 0.01 m3g-1 day-1, and wind speed has a positive correlation with the sampling rate. Under different temperature and relative humidity, the sampling rate of SIC keeps stable. The sampling rate of CIC and BIC shows a negative correlation with temperature, and GCS is influenced by all the three meteorological factors. Furthermore, long-term experiments were carried out to investigate the uptake capacity of GCS and SIC. Uptake curves show that the mass amount of sorbent in a passive sampler can influence uptake capacity. In the passive sampler, 0.9 g SIC or 0.9 g GCS can achieve stable uptake efficiency for at least 110 days with gaseous mercury concentration at or below 2 ng/m3. For mercury concentration at or below 21 ng/m3, 0.9 g SIC can maintain stable uptake efficiency for 70 days, and 0.9 g GCS can maintain stability for 45 days.