It takes two to tango: NAD+ and sirtuins in aging/longevity control

AbstractThe coupling of nicotinamide adenine dinucleotide (NAD+) breakdown and protein deacylation is a unique feature of the family of proteins called ‘sirtuins.’ This intimate connection between NAD+ and sirtuins has an ancient origin and provides a mechanistic foundation that translates the regulation of energy metabolism into aging and longevity control in diverse organisms. Although the field of sirtuin research went through intensive controversies, an increasing number of recent studies have put those controversies to rest and fully established the significance of sirtuins as an evolutionarily conserved aging/longevity regulator. The tight connection between NAD+ and sirtuins is regulated at several different levels, adding further complexity to their coordination in metabolic and aging/longevity control. Interestingly, it has been demonstrated that NAD+ availability decreases over age, reducing sirtuin activities and affecting the communication between the nucleus and mitochondria at a cellular level and also between the hypothalamus and adipose tissue at a systemic level. These dynamic cellular and systemic processes likely contribute to the development of age-associated functional decline and the pathogenesis of diseases of aging. To mitigate these age-associated problems, supplementation of key NAD+ intermediates is currently drawing significant attention. In this review article, we will summarize these important aspects of the intimate connection between NAD+ and sirtuins in aging/longevity control.</jats:p

X-ray Investigation of Low-Cycle Fatigue in Martensitic Steels

Specimens of 0.38%C steel and Fe-25%Ni alloy were put to test of their low-cycle fatigue, tensile and hardness properties, both in their tempered state. The maximum bending strain on their surfaces under which the fatigue was tested was controlled at between 1.0 and 1.6%. The X-ray diffraction and thin film electronmicroscopy methods and some other techniques were employed for the purpose. The results obtained may be summarized in two phenomena. One is similar to the contrast of annealed metals versus cold-worked metals, and the other is what is considered to characterize the tempered martensite. Both materials in tempered condition present a remarkable variation in microstructure, and the difference in microstructure is almost leveled out only in the low carbon 25%Ni alloy by the fatigue and this phenomenon is similar to the contrast of annealed metals versus cold-worked metals. But in the 0.38%C steel the difference is not leveled out even after the fatigue to failure. The results obtained are not yet adequate enough to explain the correlation between the microstructural variation and the damage fraction in a tempered martensite. The crack initiation and propagation in the 0.38%C steel and 25%Ni alloy are often related longitudinally to the edges of martensite leaves

It takes two to tango: NAD+ and sirtuins in aging/longevity control

The coupling of nicotinamide adenine dinucleotide (NAD⁺) breakdown and protein deacylation is a unique feature of the family of proteins called ‘sirtuins.’ This intimate connection between NAD⁺ and sirtuins has an ancient origin and provides a mechanistic foundation that translates the regulation of energy metabolism into aging and longevity control in diverse organisms. Although the field of sirtuin research went through intensive controversies, an increasing number of recent studies have put those controversies to rest and fully established the significance of sirtuins as an evolutionarily conserved aging/longevity regulator. The tight connection between NAD⁺ and sirtuins is regulated at several different levels, adding further complexity to their coordination in metabolic and aging/longevity control. Interestingly, it has been demonstrated that NAD⁺ availability decreases over age, reducing sirtuin activities and affecting the communication between the nucleus and mitochondria at a cellular level and also between the hypothalamus and adipose tissue at a systemic level. These dynamic cellular and systemic processes likely contribute to the development of age-associated functional decline and the pathogenesis of diseases of aging. To mitigate these age-associated problems, supplementation of key NAD⁺ intermediates is currently drawing significant attention. In this review article, we will summarize these important aspects of the intimate connection between NAD⁺ and sirtuins in aging/longevity control.National Institute on Aging (Grant AG037457)National Institute on Aging (Grant AG047902

Friends and foes: Extracellular vesicles in aging and rejuvenation

Extracellular vesicles (EVs) are released by many different cell types throughout the body and play a role in a diverse range of biological processes. EVs circulating in blood as well as in other body fluids undergo dramatic alterations over an organism\u27s lifespan that are only beginning to be elucidated. The exact nature of these changes is an area of active and intense investigation, but lacks clear consensus due to the substantial heterogeneity in EV subpopulations and insufficiencies in current technologies. Nonetheless, emerging evidence suggests that EVs regulate systemic aging as well as the pathophysiology of age-related diseases. Here, we review the current literature investigating EVs and aging with an emphasis on consequences for the maintenance of human healthspan. Intriguingly, the biological utility of EVs both in vitro and in vivo and across contexts depends on the states of the source cells or tissues. As such, EVs secreted by cells in an aged or pathological state may impose detrimental consequences on recipient cells, while EVs secreted by youthful or healthy cells may promote functional improvement. Thus, it is critical to understand both functions of EVs and tip the balance toward their beneficial effects as an antiaging intervention

Deficiency of Prdm13, a dorsomedial hypothalamus-enriched gene, mimics age-associated changes in sleep quality and adiposity

The dorsomedial hypothalamus (DMH) controls a number of essential physiological responses. We have demonstrated that the DMH plays an important role in the regulation of mammalian aging and longevity. To further dissect the molecular basis of the DMH function, we conducted microarray-based gene expression profiling with total RNA from laser-microdissected hypothalamic nuclei and tried to find the genes highly and selectively expressed in the DMH. We found neuropeptide VF precursor (Npvf),PR domain containing 13 (Prdm13), and SK1 family transcriptional corepressor (Skor1) as DMH-enriched genes. Particularly, Prdm13, a member of the Prdm family of transcription regulators, was specifically expressed in the compact region of the DMH (DMC), where Nk2 homeobox 1 (Nkx2-1) is predominantly expressed. The expression of Prdm13 in the hypothalamus increased under diet restriction, whereas it decreased during aging. Prdm13 expression also showed diurnal oscillation and was significantly upregulated in the DMH of long-lived BRASTO mice. The transcriptional activity of the Prdm13 promoter was upregulated by Nkx2-1, and knockdown of Nkx2-1 suppressed Prdm13 expression in primary hypothalamic neurons. Interestingly, DMH-specific Prdm13-knockdown mice showed significantly reduced wake time during the dark period and decreased sleep quality, which was defined by the quantity of electroencephalogram delta activity during NREM sleep. DMH-specific Prdm13-knockdown mice also exhibited progressive increases in body weight and adiposity. Our findings indicate that Prdm13/Nkx2-1-mediated signaling in the DMC declines with advanced age, leading to decreased sleep quality and increased adiposity, which mimic age-associated pathophysiology, and provides a potential link to DMH-mediated aging and longevity control in mammals

Pollution by estrogens in river and estuarine waters around Kuala Lumpur, Malaysia, and their effects on the estuarine Java-medaka, Oryzias javanicus.

Estrogens (17 B-estradiol and estrone) concentrations in river and estuarine waters around Kuala Lumpur, Malaysia were determined by enzyme-linked immunosorbent assay while estrogenic potential of the waters were ascertained by three in vitro bioassays, namely E-screen, Ishikawa cell-alkaline phosphatase and yeast estrogen screen. Moreover, hepatic vitellogenin, a precursor of yolk protein that is specific to females, were examined in male and female Java-medaka collected in the same area. 17B-estradiol and estrone concentrations were less than 6.1 ng/L and 127 ng/L, respectively. The highest 17B-estradiol equivalent activity, 284 ng/L, was detected by in vitro assay in Sungai Kuyoh, which was adjacent to a sewage plant. 17B-estradiol and estrone concentrations were not equal to their estrogenic potentials determined by in vitro assay implying the presence of other estrogenic chemicals in these waters. Hepatic vitellogenin concentrations of both male and female java-medaka were the same to laboratory-cultured individuals. Although relatively high estrogen concentrations were detected in some waters of Malaysia, these were not high enough to induce hepatic vitellogenin in male fishes. Further research, however, is necessary to cover more number of sampling sites

Sleep-wake patterns are altered with age, Prdm13 signaling in the DMH, and diet restriction in mice

Old animals display significant alterations in sleep-wake patterns such as increases in sleep fragmentation and sleep propensity. Here, we demonstrated that PR-domain containing protein 13 (Prdm13)+ neurons in the dorsomedial hypothalamus (DMH) are activated during sleep deprivation (SD) in young mice but not in old mice. Chemogenetic inhibition of Prdm13+ neurons in the DMH in young mice promotes increase in sleep attempts during SD, suggesting its involvement in sleep control. Furthermore, DMH-specifi