Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis Evolved and Became a Determinant of Ageing Diseases: Hypotheses and Lessons from Pellagra

Compartmentalized redox faults are common to ageing diseases. Dietary constituents are catabolized to NAD(H) donating electrons producing proton-based bioenergy in coevolved, cross-species and cross-organ networks. Nicotinamide and NAD deficiency from poor diet or high expenditure causes pellagra, an ageing and dementing disorder with lost robustness to infection and stress. Nicotinamide and stress induce Nicotinamide-N-methyltransferase (NNMT) improving choline retention but consume methyl groups. High NNMT activity is linked to Parkinson's, cancers, and diseases of affluence. Optimising nicotinamide and choline/methyl group availability is important for brain development and increased during our evolution raising metabolic and methylome ceilings through dietary/metabolic symbiotic means but strict energy constraints remain and life-history tradeoffs are the rule. An optimal energy, NAD and methyl group supply, avoiding hypo and hyper-vitaminoses nicotinamide and choline, is important to healthy ageing and avoids utilising double-edged symbionts or uncontrolled autophagy or reversions to fermentation reactions in inflammatory and cancerous tissue that all redistribute NAD(P)(H), but incur high allostatic costs

A Search for the Damped Ly-alpha Absorber at z=1.86 toward QSO 1244+3443 with NICMOS

We have carried out a high-resolution imaging search for the galaxy associated with the damped Lyman-alpha (DLA) absorber at z=1.859 toward the z_{em}=2.48 quasar QSO 1244+3443, using the HST and the NICMOS. Images were obtained in the broad filter F160W and the narrow filter F187N with camera 2 on NICMOS with the goal of detecting the rest-frame optical continuum and the H-alpha line emission from the DLA. After PSF subtraction, two weak features are seen at projected separations of 0.16-0.24" from the quasar. Parts of these features may be associated with the DLA absorber, although we cannot completely rule out that they could be artifacts of the point spread function (PSF). If associated with the DLA, the objects would be ~1-2 h_{70}^{-1} kpc in size with integrated flux densities of 2.5 and 3.3 mu Jy in the F160W filter, implying luminosities at lambda_{central}=5600 A in the DLA rest frame of 4.4-5.9 x 10^{9} h_{70}^{-2} L_{solar} at z=1.86, for q0=0.5. However, no significant H-alpha line emission is seen from these objects, suggesting low star formation rates (SFRs). Our 3 sigma upper limit on the SFR in the DLA is 1.3 h_{70}^{-2} M_{solar}/yr for q0 = 0.5 (2.4 h_{70}^{-2} M_{solar} yr^{-1} for q0 = 0.1). This together with our earlier result for LBQS 1210+1731 mark a significant improvement over previous constraints on the star formation rates of DLAs. A combination of low SFR and some dust extinction is likely to be responsible for the lack of H-alpha emission. Alternatively, the objects, may be associated with the quasar host galaxy. In any case, our observations suggest that the DLA is not a large bright proto-disk, but a compact object or a low-surface brightness galaxy. If the two features are PSF artifacts then the constraints on DLA properties are even more severe.Comment: 28 pages, 9 figures. Accepted for publication in The Astrophysical Journal. Figures are given at a slightly lower resolution here, to decrease file sizes. The higher resolution versions can be found in the Ap

New Hope: A Thoughtful and Effective Approach to Make Work Pay

This paper makes the case for a national program offering the kind of work supports that were part of the New Hope program, a policy experiment that operated for three years in Milwaukee, Wisconsin. Our policy, like New Hope, would provide a set of work supports for full-time workers-both parents and nonparents, men and women-that would lift them out of poverty as well as provide essential benefits in the form of health insurance and child-care subsidies for people who needed them. Across all of the people offered the chance to participate in the New Hope program, including single men, work increased and poverty rates fell. Children in New Hope families performed better in school, were more cooperative and independent and had fewer behavior problems and loftier schooling expectations than children in the control group. Because boys have a higher risk of school failure and behavior problems than girls do, it is noteworthy that New Hope was especially successful in improving their school performance and behavior. With its positive effects on children\u27s achievement and behavior, a scaled-up New Hope program may well help to break the cycle of poverty for a sizeable number of American families in the next generation. With reasonable assumptions about the long-term value of New Hope\u27s positive impacts on children, New Hope easily passes a cost-benefit test

Poverty and Pellagra’s Penumbras

Pellagra has largely been forgotten. This is unfortunate as important lessons are to be learnt about the diseases and social and economic consequences of poverty – and for the root cause of poverty (and of affluence) – that involve dietary nicotinamide and nicotinamide adenine dinucleotide (NAD) homeostasis. NAD disruption can occur not only from poor diet but from increased consumption from genotoxic, infectious and metabolic stresses. NAD deficiency is closely linked to poor physical and intellectual development, premature ageing and diseases of ageing. Acute infections, many with NAD-consuming toxins, that may differentially affect the NAD-depleted, now include COVID-19. Some Covid manifestations, such as myoclonic encephalopathy and “Long Covid,” resemble pellagra clinically and biochemically as both have disturbed nicotinic and tryptophan metabolism. Symbionts that supply nicotinic acid, such as TB and some gut micro-organisms, can become dysbiotic if the diet is very deficient in milk and meat, as it is for 1–2 billion or more. High doses of nicotinamide lead to inhibition of NAD-consuming enzymes and excessive induction of nicotinamide-n-methyl transferase (NNMT) with consequent effects on the methylome: this gives a mechanism for an unrecognised hypervitaminosis-B3 with adverse effects of nicotinamide overload for consumers on a high meat diet with “fortified” foods and “high energy” drinks. Methods of measuring NAD metabolism routinely for screening the populations at risk of deficiency and in metabolically ill or infectious disease patients should be developed urgently. Successful intervention should improve human capital and prevent many aspects of poverty, reduce discrimination and even the drive to emigrate

Meat and Vitamin B3: Getting a Grip on Engel’s Curve

We evolved from herbivores to a meat eating “commons” in hunter-gatherer days and then to a non-egalitarian meat power struggle between classes and countries. Egalitarian-ism, trans-egalitarianism and extremes of inequality and hierarchy revolve around the fair-unfair distribution of meat surpluses and ownership of the means of meat production. Poor people on poor diets with too few micronutrients may explain many inequalities of human capital, height and health and divergent development of individuals and nations. Learning from past successes and collapses from switching trophic levels the lesson is that meat moderation toward the top of Engel’s curves, not calorie-centrism, is the best recipe for countries and classes. Improved health with longer lives and higher crystallised intelligence comes with an ample supply of micronutrients from animal products namely iron, zinc, vitamin A, vitamin B12 and other methyl-donors (such as choline), and nicotinamide (vitamin B3). We concentrate on nicotinamide whose deficits cause the degenerative condition pellagra that manifests as poor emotional and degenerative cognitive states with stunted lives and complex antisocial and dysbiotic effects caused by and causing poverty

Inequality: The Dangers of Meat Haves and Have-Nots in a Nicotinamide-Adenine-Dinucleotide World

Our evolution and recent history can be seen as a “World Hunt” for meat as part of an omnivorous diet. Meat contains key micronutrients namely Nicotinamide (vitamin B3) and methyl-donors with deficits causing pellagra, an archetypal disease of poverty. Inequality is a leading ultimate risk factor invoked in the aetiology of common diseases let alone threats from climate change and pandemic triggered catastrophes. We hypothesize that the origin of inequality was our evolutionary and nutritional move from equal to unequal sharing of the meat supply some 10–20 thousand years ago. High meat intake may have bioengineered powerful ruling classes and lower intake the proletariat with higher fertility, but inferior (brain) health. A fairer quantity of a safer meat intake in future should moderate global variances of fertility, height, health, and prosperity. Death rates of acute infections including emergent zoonoses (such as COVID-19) and chronic infections (such as TB) should fall as might the incidence of some diseases of affluence. Meat justice by improving human capital could make redundant superficial markers, such as skin colour, used to discriminate against peoples and heal a divided world

NICMOS Imaging of a Damped Lyman-alpha Absorber at z=1.89 toward LBQS 1210+1731 : Constraints on Size and Star Formation Rate

We report results of a high-resolution imaging search (in rest frame H-$\alpha$ and optical continuum) for the galaxy associated with the damped Lyman-$\alpha$ (DLA) absorber at $z=1.892$ toward the $z_{em}=2.543$ quasar LBQS 1210+1731, using HST/NICMOS. After PSF subtraction, a feature is seen in both the broad-band and narrow-band images, at a projected separation of 0.25\arcsec from the quasar. If associated with the DLA, the object would be $\approx 2-3$ $h_{70}^{-1}$ kpc in size with a flux of $9.8 \pm 2.4$ $\mu$Jy in the F160W filter, implying a luminosity at $\lambda_{central}=5500$ {\AA} in the rest frame of $1.5 \times 10^{10}$ $h_{70}^{-2}$ L$_{\odot}$ at $z=1.89$, for $q_{0}=0.5$. However, no significant H-$\alpha$ emission is seen, suggesting a low star formation rate (SFR) (3 $\sigma$ upper limit of 4.0 $h_{70}^{-2}$ M$_{\odot}$ yr$^{-1}$), or very high dust obscuration. Alternatively, the object may be associated with the host galaxy of the quasar. H-band images obtained with the NICMOS camera 2 coronagraph show a much fainter structure $\approx 4-5$ $h_{70}^{-1}$ kpc in size and containing four knots of continuum emission, located 0.7\arcsec away from the quasar. We have probed regions far closer to the quasar sight-line than in most previous studies of high-redshift intervening DLAs. The two objects we report mark the closest detected high-redshift DLA candidates yet to any quasar sight line. If the features in our images are associated with the DLA, they suggest faint, compact, somewhat clumpy objects rather than large, well-formed proto-galactic disks or spheroids.Comment: 52 pages of text, 19 figures, To be published in Astrophysical Journal (accepted Dec. 8, 1999