Does eating less make you live longer?

a woman eating a plate of noodles with a fork


The complexity of aging is hard to be captured. However, apart from its tissue-specific features, a structural and functional progressive decline of the whole organism that leads to death, often preceded by a phase of chronic morbidity, characterizes the common process of aging. Therefore, the research goal of scientists in the field moved from the search for strategies able to extend longevity to those ensuring healthy aging associated with a longer lifespan referred to as “healthspan”.

The aging process is plastic and can be tuned by multiple mechanisms including dietary and genetic interventions. To date, the most robust approach, efficient in warding off the cellular markers of aging, is calorie restriction (CR).

Here, after a preliminary presentation of the major debate originated by CR, we concisely overviewed the recent results of CR treatment on humans. We also provided an update on the molecular mechanisms involved by CR and the effects on some of the age-associated cellular markers. Finally, we reviewed a number of tested CR mimetics and concluded with an evaluation of future applications of such dietary approach.

Quercetin reduces blood pressure in hypertensive subjects

black currant berries


Epidemiological studies report that quercetin, an antioxidant flavonol found in apples, berries, and onions, is associated with reduced risk of coronary heart disease and stroke. Quercetin supplementation also reduces blood pressure in hypertensive rodents. The efficacy of quercetin supplementation to lower blood pressure in hypertensive humans has never been evaluated.

We tested the hypothesis that quercetin supplementation reduces blood pressure in hypertensive patients. We then determined whether the antihypertensive effect of quercetin is associated with reductions in systemic oxidant stress. Men and women with prehypertension (n = 19) and stage 1 hypertension (n = 22) were enrolled in a randomized, double-blind, placebo-controlled, crossover study to test the efficacy of 730 mg quercetin/d for 28 d vs. placebo. Blood pressure (mm Hg, systolic/diastolic) at enrollment was 137 +/- 2/86 +/- 1 in prehypertensives and 148 +/- 2/96 +/- 1 in stage 1 hypertensive subjects.

Blood pressure was not altered in prehypertensive patients after quercetin supplementation. In contrast, reductions in (P < 0.01) systolic (-7 +/- 2 mm Hg), diastolic (-5 +/- 2 mm Hg), and mean arterial pressures (-5 +/- 2 mm Hg) were observed in stage 1 hypertensive patients after quercetin treatment. However, indices of oxidant stress measured in the plasma and urine were not affected by quercetin.

These data are the first to our knowledge to show that quercetin supplementation reduces blood pressure in hypertensive subjects. Contrary to animal-based studies, there was no quercetin-evoked reduction in systemic markers of oxidative stress. 

SOURCE: Journal of Nutrition

NAD deficiency + niacin supplementation

Abstract modern vase with leaf


Background: Congenital malformations can be manifested as combinations of phenotypes that co-occur more often than expected by chance. In many such cases, it has proved difficult to identify a genetic cause. We sought the genetic cause of cardiac, vertebral, and renal defects, among others, in unrelated patients.

Methods: We used genomic sequencing to identify potentially pathogenic gene variants in families in which a person had multiple congenital malformations. We tested the function of the variant by using assays of in vitro enzyme activity and by quantifying metabolites in patient plasma. We engineered mouse models with similar variants using the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system.

Results: Variants were identified in two genes that encode enzymes of the kynurenine pathway, 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO) and kynureninase (KYNU). Three patients carried homozygous variants predicting loss-of-function changes in the HAAO or KYNU proteins (HAAO p.D162*, HAAO p.W186*, or KYNU p.V57Efs*21). Another patient carried heterozygous KYNU variants (p.Y156* and p.F349Kfs*4). The mutant enzymes had greatly reduced activity in vitro. Nicotinamide adenine dinucleotide (NAD) is synthesized de novo from tryptophan through the kynurenine pathway. The patients had reduced levels of circulating NAD. Defects similar to those in the patients developed in the embryos of Haao-null or Kynu-null mice owing to NAD deficiency. In null mice, the prevention of NAD deficiency during gestation averted defects.

Conclusions: Disruption of NAD synthesis caused a deficiency of NAD and congenital malformations in humans and mice. Niacin supplementation during gestation prevented the malformations in mice.


EDITOR’S NOTE: Apparent restoration of NAD synthesis was achieved here with a readily available supplement, niacin (vitamin B3).

Happiness and Aging in the United States


The past decade has brought increasing concern, in countries all over the world, of declines in mental health and well-being. Across countries, chronic depression and suicide rates peak in midlife. In the U.S., deaths of despair are most likely to occur in these years, and the patterns are robustly associated with unhappiness and stress. There is also a less-known relationship between well-being and longevity among the elderly, particularly for those over age 70.

In this paper, we analyze several different data sets for the U.S. and provide extensive evidence on the middle age patterns, how they differ across the married and unmarried, and review new work on the elderly. The relationship between well-being and aging has a robust association with trends that can ruin lives and shorten life spans. It applies to much of the world’s population and links to behaviors and outcomes that merit the attention of scholars and policymakers alike.

The hallmarks of aging

a cartoon of a bear in snow wearing a red scarf


Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution.

This review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects.

At first sight, cancer and aging may seem to be opposite processes: cancer is the consequence of an aberrant gain of cellular fitness, whereas aging is characterized by a loss of fitness. At a deeper level, however, cancer and aging share common origins. The time-dependent accumulation of cellular damage is widely considered to be the general cause of aging. Concomitantly, cellular damage may occasionally provide aberrant advantages to certain cells, which can eventually produce cancer. Therefore, cancer and aging can be regarded as two different manifestations of the same underlying process — namely, the accumulation of cellular damage. In addition, several of the pathologies associated with aging, such as atherosclerosis and inflammation, involve uncontrolled cellular overgrowth or hyperactivity.

Based on this conceptual framework, several critical questions have arisen in the field of aging regarding the physiological sources of aging-causing damage, the compensatory responses that try to re-establish homeostasis, the interconnection between the different types of damage and compensatory responses, and the possibilities to intervene exogenously to delay aging. We propose nine candidate hallmarks that are generally considered to contribute to the aging process and together determine the aging phenotype. Each hallmark should ideally fulfill the following criteria: (1) it should manifest during normal aging; (2) its experimental aggravation should accelerate aging; and (3) its experimental amelioration should retard the normal aging process and hence increase healthy lifespan.