Senescence is a condition of cell cycle arrest that increases inflammation and contributes to the development of chronic diseases in the aging human body. While several compounds described as senolytics and senomorphics produce health benefits by reducing the burden of senescence, less attention has been devoted to lifestyle interventions that produce similar effects. We describe here the effects of exercise, nutrition, caloric restriction, intermittent fasting, phytochemicals from natural products, prebiotics and probiotics, and adequate sleep on senescence in model organisms and humans. These interventions can be integrated within a healthy lifestyle to reduce senescence and inflammation and delay the consequences of aging.

The inflammasome has been mainly studied in innate immune cells in which it senses microbes and cellular damage, and induces secretion of pro-inflammatory cytokines. This process induces an inflammatory response that is critical for the resolution of infections and repair of tissue damage following injury. Recent studies indicate that inflammasome complex formation also participates in many other cellular and physiological processes beyond modulation of inflammation, such as autophagy, metabolism, eicosanoids production, and phagosome maturation.

The nasal cavity and turbinates play important physiological functions by filtering, warming and humidifying inhaled air. Paranasal sinuses continually produce nitric oxide (NO), a reactive oxygen species that diffuses to the bronchi and lungs to produce bronchodilatory and vasodilatory effects. Studies indicate that NO may also help to reduce respiratory tract infection by inactivating viruses and inhibiting their replication in epithelial cells. In view of the pandemic caused by the novel coronavirus (SARS-CoV-2), clinical trials have been designed to examine the effects of inhaled nitric oxide in COVID-19 subjects. We discuss here additional lifestyle factors such as mouth breathing which may affect the antiviral response against SARS-CoV-2 by bypassing the filtering effect of the nose and by decreasing NO levels in the airways. Simple devices that promote nasal breathing during sleep may help prevent the common cold, suggesting potential benefits against coronavirus infection. In the absence of effective treatments against COVID-19, the alternative strategies proposed here should be considered and studied in more detail.

Living organisms have evolved within the natural electromagnetic fields (EMFs) of the earth which comprise the global atmospheric electrical circuit, Schumann resonances (SRs) and the geomagnetic field. Research suggests that the circadian rhythm, which controls several physiological functions in the human body, can be influenced by light but also by the earth's EMFs. Cyclic solar disturbances, including sunspots and seasonal weakening of the geomagnetic field, can affect human health, possibly by disrupting the circadian rhythm and downstream physiological functions. Severe disruption of the circadian rhythm increases inflammation which can induce fatigue, fever and flu-like symptoms in a fraction of the population and worsen existing symptoms in old and diseased individuals, leading to periodic spikes of infectious and chronic diseases. Possible mechanisms underlying sensing of the earth's EMFs involve entrainment via electrons and electromagnetic waves, light-dependent radical pair formation in retina cryptochromes, and paramagnetic magnetite nanoparticles. Factors such as electromagnetic pollution from wireless devices, base antennas and low orbit internet satellites, shielding by non-conductive materials used in shoes and buildings, and local geomagnetic anomalies may also affect sensing of the earth's EMFs by the human body and contribute to circadian rhythm disruption and disease development.

The nematode Caenorhabditis elegans is a useful model to study aging due to its short lifespan, ease of manipulation, and available genetic tools. Several molecules and extracts derived from plants and fungi extend the lifespan of C. elegans by modulating aging-related pathways that are conserved in more complex organisms. Modulation of aging pathways leads to activation of autophagy, mitochondrial biogenesis and expression of antioxidant and detoxifying enzymes in a manner similar to caloric restriction. Low and moderate concentrations of plant and fungal molecules usually extend lifespan, while high concentrations are detrimental, consistent with a lifespan-modulating mechanism involving hormesis. We review here molecules and extracts derived from plants and fungi that extend the lifespan of C. elegans, and explore the possibility that these natural substances may produce health benefits in humans.

Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1β and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-β1-induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1-treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, HSM pretreatment markedly reduces bleomycin-induced lung injury and fibrosis in mice. Accordingly, HSM reduces inflammatory cell accumulation in bronchoalveolar lavage fluid and proinflammatory cytokines levels in lung tissues. The HSM extract also significantly reduces TGF-β1 in lung tissues, and this effect is accompanied by decreased collagen 3α1 and α-SMA levels. Moreover, HSM reduces expression of the NLRP3 inflammasome and P2X7R in lung tissues, whereas it enhances expression of superoxide dismutase. These findings suggest that HSM may be used for the treatment of pulmonary inflammation and fibrosis.

Ectopic calcification is associated with various human diseases, including atherosclerosis, cancer, chronic kidney disease, and diabetes mellitus. Although mineral nanoparticles have been detected in calcified blood vessels, the nature and role of these particles in the human body remain unclear. Here we show for the first time that human kidney tissues obtained from end-stage chronic kidney disease or renal cancer patients contain round, multilamellar mineral particles of 50 to 1,500 nm, whereas no particles are observed in healthy controls. The mineral particles are found mainly in the extracellular matrix surrounding the convoluted tubules, collecting ducts and loops of Henle as well as within the cytoplasm of tubule-delineating cells, and consist of polycrystalline calcium phosphate similar to the mineral found in bones and ectopic calcifications. The kidney mineral nanoparticles contain several serum proteins that inhibit ectopic calcification in body fluids, including albumin, fetuin-A, and apolipoprotein A1. Since the mineralo-organic nanoparticles are found not only within calcified deposits but also in areas devoid of microscopic calcifications, our observations indicate that the nanoparticles may represent precursors of calcification and renal stones in humans.

Calcium phosphate-based mineralo-organic particles form spontaneously in the body and may represent precursors of ectopic calcification. We have shown earlier that these particles induce activation of caspase-1 and secretion of IL-1β by macrophages. However, whether the particles may produce other effects on immune cells is unclear. Here, we show that these particles induce the release of neutrophil extracellular traps (NETs) in a size-dependent manner by human neutrophils. Intracellular production of reactive oxygen species is required for particle-induced NET release by neutrophils. NETs contain the high-mobility group protein B1 (HMGB1), a DNA-binding protein capable of inducing secretion of TNF-α by a monocyte/macrophage cell line and primary macrophages. HMGB1 functions as a ligand of Toll-like receptors 2 and 4 on macrophages, leading to activation of the MyD88 pathway and TNF-α production. Furthermore, HMGB1 is critical to activate the particle-induced pro-inflammatory cascade in the peritoneum of mice. These results indicate that mineral particles promote pro-inflammatory responses by engaging neutrophils and macrophages via signaling of danger signals through NETs.

We examined the effects of an Antrodia cinnamomea ethanol extract (ACEE) on lung cancer cells in vitro and tumor growth in vivo. ACEE produced dose-dependent cytotoxic effects and induced apoptosis in Lewis lung carcinoma (LLC) cells. ACEE treatment increased expression of p53 and Bax, as well as cleavage of caspase-3 and PARP, while reducing expression of survivin and Bcl-2. ACEE also reduced the levels of JAK2 and phosphorylated STAT3 in LLC cells. In a murine allograft tumor model, oral administration of ACEE significantly inhibited LLC tumor growth and metastasis without affecting serum biological parameters or body weight. ACEE increased cleavage of caspase-3 in murine tumors, while decreasing STAT3 phosphorylation. In addition, ACEE reduced the growth of human tumor xenografts in nude mice. Our findings therefore indicate that ACEE inhibits lung tumor growth and metastasis by inducing apoptosis and by inhibiting the STAT3 signaling pathway in cancer cells.

This corrects the article DOI: 10.1038/ncomms8489.