17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex

Harrison, David E.; Strong, Randy; Reifsnyder, Peter C.; Kumar, Navasuja; Fernández, Elízabeth; Flurkey, Kevin; Javors, Martin A.; Lopez‐Cruzan, Marisa; Macchiarini, Francesca; Nelson, James F.; Bitto, Alessandro; Sindler, Amy L.; Cortopassi, Gino A; Kavanagh, Kylie; Leng, Lin; Bucala, Richard; Rosenthal, Nadia; Salmon, Adam B.; Stearns, Timothy M.; Bogue, Molly A.; Miller, Richard A.

doi:10.1111/acel.13328

Cited by 73 publications

(65 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chronic N-acetylcysteine treatment also reduced circulating IGF-1 by 20%-50%, depending on mouse strain (Ackert-Bicknell et al, 2004). The estrogen 17-α-estradiol extended male median lifespan (by 19%) when started late in life (16 and 20 months), but also caused a 20% weight drop (Harrison et al, 2021). Similar but smaller weight loss and life span extension was found at a lower dose of 17-α-estradiol .…”

Section: Other Treatments In Micementioning

confidence: 70%

“…Aging cell 13, 273-282. Harrison, D.E., Strong, R., Reifsnyder, P., Kumar, N., Fernandez, E., Flurkey, K., Javors, M.A., Lopez-Cruzan, M., Macchiarini, F., Nelson, J.F., 2021. 17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging cell, e13328.…”

Section: Discussionmentioning

confidence: 98%

“…Feeding mice the NAD+ precursor NMN also suppressed body weight gain by accelerating metabolism . The NIA Interventions Testing Program could replicate the weight loss, but not the life extension with NR supplementation (Harrison et al, 2021). The age-related decrease in NAD+ is mediated by increased expression of the NADase CD38 (Camacho-Pereira et al, 2016).…”

Section: Interventions In Mice -Nad+mentioning

confidence: 99%

See 2 more Smart Citations

The caloric restriction fallacy, rodent diet aids and the tumor suppression theory of aging

Wolf¹

2021

Preprint

View full text Add to dashboard Cite

Understanding the molecular mechanisms of normal aging is a prerequisite to significantly increase human health span. Caloric restriction (CR), which delays aging in most animal models, serves as a yardstick to evaluate interventions extending life span. However, mice given unlimited access to food suffer severe obesity and benefits from CR might be through reducing obesity-associated mortality. Health gains from CR depend on the control mice being gluttonous enough and less obese mouse strains benefit far less from CR. Most pharmacologic interventions reported to mimic CR and increase life span in mice, including resveratrol, rapamycin, nicotinamide mononucleotide and metformin, also reduce mouse body weight. In primates, CR does not delay aging unless the control group is eating enough to suffer from obesity-related disease. Human survival peaks at a BMI achievable without CR. CR mimetics are just diet aids and CR should not be regarded as increasing longevity in healthy weight individuals. Instead, I propose the tumor suppression theory of aging: most phenotypes of aging are the consequence of tumor-suppressive cell senescence that has evolved to limit the tumorigenic potential of clonally expanding cells. A variant of the somatic mutation theory of aging, oncogenic mutations and clonal expansion (opposed to functional impairment) are postulated as the most relevant consequence of somatic mutations. Irreversible cell cycle arrest, accumulating senescent cells, the senescence-associated secretory phenotype and subsequent stem cell depletion eventually cause tissue dysfunction, loss of regeneration and the majority, if not most, phenotypes of aging.

show abstract

Section: Other Treatments In Micementioning

confidence: 70%

Section: Discussionmentioning

confidence: 98%

Section: Interventions In Mice -Nad+mentioning

confidence: 99%

See 1 more Smart Citation

The caloric restriction fallacy, rodent diet aids and the tumor suppression theory of aging

Wolf¹

2021

Preprint

View full text Add to dashboard Cite

show abstract

“… 14 Nevertheless, a recent study provided a negative result of NR effects on lifespan in both male and female mice at the doses tested. 15 …”

Section: Nad + In Healthy Agingmentioning

confidence: 99%

“…14 Nevertheless, a recent study provided a negative result of NR effects on lifespan in both male and female mice at the doses tested. 15 A recent important finding is that the plasma levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a key NAD + biosynthetic enzyme located in extracellular vesicles (EVs), were declined with age in both mice and humans, injuring function of specific tissues. ) by LDH, coupled NADH oxidation, increasing NAD + /NADH ratio and preserving glycolysis at G-3-PD step; pyruvate also inhibits the sorbitol pathway by declining AR activity, decreasing NAD + consumption and restores the pentose phosphate pathway in cytosol, raising GSH/GSSG ratio.…”

Section: Nad + In Healthy Agingmentioning

confidence: 99%

NAD⁺, Senolytics, or Pyruvate for Healthy Aging?

Zhou

2021

Nutr Metab Insights

View full text Add to dashboard Cite

In last decades, healthy aging has become one of research hotspots in life science. It is well known that the nicotinamide adenine dinucleotide oxidized form (NAD+) level in cells decreases with aging and aging-related diseases. Several years ago, one of NAD+ precursors was first demonstrated with its new role in DNA damage repairing in mice, restoring old mice to their physical state at young ones. The finding encourages extensive studies in animal models and patients. NAD+ and its precursors have been popular products in nutrition markets. Alternatively, it was also evidenced that clearance of cellular senescence by senolytics preserved multiorgan (kidney and heart) function and extended healthy lifespan in mice. Subsequent studies confirmed findings in elderly patients subjected with idiopathic pulmonary fibrosis. The senolytic therapy is now focused on various diseases in animal and clinical studies. However, pyruvate, as both a NAD+ substitute and a new senolytic, may be advantageous, on the equimolar basis, over current products above in preventing and treating diseases and aging. Pyruvate-enriched fluids, particularly pyruvate oral rehydration salt, may be a novel intervention for diseases and aging besides critical care. Albeit the direct evidence that benefits healthy aging is still limited to date, pyruvate, as both NAD+ provider and senolytic agent, warrants intensive research to compare NAD+ or senolytics for healthy aging, specifically on the equimolar basis, in effective blood levels. This review briefly discussed the recognition of healthy aging by comparing NAD+ and Senolytics with sodium pyruvate from the clinical point of view.

show abstract

Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias

Yassine

Self

Kerman

et al. 2022

Alzheimer's & Dementia

View full text Add to dashboard Cite

Disturbances in the brain's capacity to meet its energy demand increase the risk of synaptic loss, neurodegeneration, and cognitive decline. Nutritional and metabolic interventions that target metabolic pathways combined with diagnostics to identify deficits in cerebral bioenergetics may therefore offer novel therapeutic potential for Alzheimer's disease (AD) prevention and management. Many diet-derived natural bioactive components can govern cellular energy metabolism but their effects on brain aging are not clear. This review examines how nutritional metabolism can regulate brain bioenergetics and mitigate AD risk. We focus on leading mechanisms of cerebral bioenergetic breakdown in the aging brain at the cellular level, as well as the putative causes and consequences of disturbed bioenergetics, particularly at the blood-brain barrier with implications for nutrient brain delivery and nutritional interventions. Novel therapeutic nutrition approaches including diet patterns are provided, integrating studies of the gut microbiome, neuroimaging, and other biomarkers to guide future personalized nutritional interventions.

show abstract

17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 73 publications

References 46 publications

The caloric restriction fallacy, rodent diet aids and the tumor suppression theory of aging

The caloric restriction fallacy, rodent diet aids and the tumor suppression theory of aging

NAD⁺, Senolytics, or Pyruvate for Healthy Aging?

Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias

Contact Info

Product

Resources

About

17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 73 publications

References 46 publications

The caloric restriction fallacy, rodent diet aids and the tumor suppression theory of aging

The caloric restriction fallacy, rodent diet aids and the tumor suppression theory of aging

NAD+, Senolytics, or Pyruvate for Healthy Aging?

Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias

Contact Info

Product

Resources

About

NAD⁺, Senolytics, or Pyruvate for Healthy Aging?