Quest for a Long Life: Paradoxes and Essentials of Evolving Longevity

Among the countries in the developed world, Japan has the longest mean lifespan for women; however, the nation has encountered serious problems in policy and economics, as well as in managing medical care for its aging population. Aging is inevitable, but it also constitutes a major challenge in modern biology and medicine. In the treatment of geriatric patients, an understanding of the fundamental biological mechanisms of aging and longevity is crucial for the effective treatment and prevention of diseases and disorders, including dementia, osteoporosis, and sarcopenia. To address the most basic questions about aging, including determinants of lifespan and the identity of critical genes and anti-aging factors, we discuss paradoxical phenomena in the biology of longevity, with a particular focus on "time" and "size" of organisms. We also discuss essential factors and/or activities associated with anti-aging mechanisms in connection with brain function in adults and the elderly. Finally, we discuss unique features of the Shc gene family, which is involved in longevity determination, brain size restriction, cognitive functions, and evolution. The aim of this paper is to offer some insight into various problems in gerontology and geriatrics for future research

Selective upregulation of p66-Shc gene expression in the liver and brain of aged rats.

The phosphotyrosine signaling followed by various receptor activations conforms a unique signaling platform during metazoan evolution, and is crucial for animal development, maturation, and aging. Shc is the most versatile bipartite phosphotyrosine signal adaptor harboring phosphotrosine-biding (PTB) and Src-homology2 (SH2) domains. Among the Shc adaptor family members, p66-Shc is of potential interest in aging studies, since its deletion in mice resulted in a longer lifespan and/or higher quality of life in later stages of life. However, a few studies have examined the gene expression profiles of p66-Shc in aging tissues. Here, we quantified the expression levels of transcripts of Shc-related isoforms in the liver and brain of young adult, middle-aged, and aged rats, and found that p66-Shc gene expression is specifically up-regulated in the aged liver and brain. In the aged liver tissue, p66-Shc expression was also evident at the protein level, and accumulated in the soluble fraction of the aged tissue. These results indicate that p66-Shc is not only related to animal longevity but also affected during aging, and thus the repression of p66-Shc could become a potential target for an anti-aging strategy

Cloning of rat GADD45 gene and induction analysis following ionizing radiation in vivo

AbstractA gene encoded GADD45 was isolated from rat and revealed four exons along with a p53 binding consensus sequence and a putative AP-1 site in the third intron. This suggests that the rat GADD45 gene is also involved in the p53 signal pathway related to the G1 cell cycle checkpoint. The rat GADD45 mRNA was induced within 30 min in liver and increased as a function of γ-irradiation. We found that mRNA expression differed substantially in a variety of tissues (brain, liver, kidney, and spleen). The finding of in vivo induction of GADD45 gene may provide insight into the role of GADD45 gene in DNA repair

Intermediate-Mass-Elements in Young Supernova Remnants Reveal Neutron Star Kicks by Asymmetric Explosions

The birth properties of neutron stars yield important information on the still debated physical processes that trigger the explosion and on intrinsic neutron-star physics. These properties include the high space velocities of young neutron stars with average values of several 100 km/s, whose underlying "kick" mechanism is not finally clarified. There are two competing possibilities that could accelerate NSs during their birth: anisotropic ejection of either stellar debris or neutrinos. We here present new evidence from X-ray measurements that chemical elements between silicon and calcium in six young gaseous supernova remnants are preferentially expelled opposite to the direction of neutron star motion. There is no correlation between the kick velocities and magnetic field strengths of these neutron stars. Our results support a hydrodynamic origin of neutron-star kicks connected to asymmetric explosive mass ejection, and they conflict with neutron-star acceleration scenarios that invoke anisotropic neutrino emission caused by particle and nuclear physics in combination with very strong neutron-star magnetic fields.Comment: 24 pages, 12 figures, accepted for publication in The Astrophysical Journa

Metagenomics reveals global-scale contrasts in nitrogen cycling and cyanobacterial light-harvesting mechanisms in glacier cryoconite

BACKGROUND: Cryoconite granules are mineral–microbial aggregates found on glacier surfaces worldwide and are hotspots of biogeochemical reactions in glacier ecosystems. However, despite their importance within glacier ecosystems, the geographical diversity of taxonomic assemblages and metabolic potential of cryoconite communities around the globe remain unclear. In particular, the genomic content of cryoconite communities on Asia’s high mountain glaciers, which represent a substantial portion of Earth’s ice masses, has rarely been reported. Therefore, in this study, to elucidate the taxonomic and ecological diversities of cryoconite bacterial consortia on a global scale, we conducted shotgun metagenomic sequencing of cryoconite acquired from a range of geographical areas comprising Polar (Arctic and Antarctic) and Asian alpine regions. RESULTS: Our metagenomic data indicate that compositions of both bacterial taxa and functional genes are particularly distinctive for Asian cryoconite. Read abundance of the genes responsible for denitrification was significantly more abundant in Asian cryoconite than the Polar cryoconite, implying that denitrification is more enhanced in Asian glaciers. The taxonomic composition of Cyanobacteria, the key primary producers in cryoconite communities, also differs between the Polar and Asian samples. Analyses on the metagenome-assembled genomes and fluorescence emission spectra reveal that Asian cryoconite is dominated by multiple cyanobacterial lineages possessing phycoerythrin, a green light-harvesting component for photosynthesis. In contrast, Polar cryoconite is dominated by a single cyanobacterial species Phormidesmis priestleyi that does not possess phycoerythrin. These findings suggest that the assemblage of cryoconite bacterial communities respond to regional- or glacier-specific physicochemical conditions, such as the availability of nutrients (e.g., nitrate and dissolved organic carbon) and light (i.e., incident shortwave radiation). CONCLUSIONS: Our genome-resolved metagenomics provides the first characterization of the taxonomic and metabolic diversities of cryoconite from contrasting geographical areas, highlighted by the distinct light-harvesting approaches of Cyanobacteria and nitrogen utilization between Polar and Asian cryoconite, and implies the existence of environmental controls on the assemblage of cryoconite communities. These findings deepen our understanding of the biodiversity and biogeochemical cycles of glacier ecosystems, which are susceptible to ongoing climate change and glacier decline, on a global scale. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40168-022-01238-7

Root PRR7 improves the accuracy of the shoot circadian clock through nutrient transport

The circadian clock allows plants to anticipate and adapt to periodic environmental changes. Organ- and tissue-specific properties of the circadian clock and shoot-to-root circadian signaling have been reported. While this long-distance signaling is thought to coordinate physiological functions across tissues, little is known about the feedback regulation of the root clock on the shoot clock in the hierarchical circadian network. Here, we show that the plant circadian clock conveys circadian information between shoots and roots through sucrose and K⁺. We also demonstrate that K+ transport from roots suppresses the variance of period length in shoots and then improves the accuracy of the shoot circadian clock. Sucrose measurements and qPCR showed that root sucrose accumulation was regulated by the circadian clock. Furthermore, root circadian clock genes, including PSEUDO-RESPONSE REGULATOR7 (PRR7), were regulated by sucrose, suggesting the involvement of sucrose from the shoot in the regulation of root clock gene expression. Therefore, we performed time-series measurements of xylem sap and micrografting experiments using prr7 mutants and showed that root PRR7 regulates K⁺ transport and suppresses variance of period length in the shoot. Our modeling analysis supports the idea that root-to-shoot signaling contributes to the precision of the shoot circadian clock. We performed micrografting experiments that illustrated how root PRR7 plays key roles in maintaining the accuracy of shoot circadian rhythms. We thus present a novel directional signaling pathway for circadian information from roots to shoots and propose that plants modulate physiological events in a timely manner through various timekeeping mechanisms