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View article: Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice
Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice Open
Mice bred in 2021 were tested by the Interventions Testing Program (ITP) for possible lifespan benefits of 2BAct (2BA), dichloroacetate (DCA), Epicatechin (EPI), Forskolin (FSK), Halofuginone (HAL) and Mitoglitazone (MIT). All agents were …
View article: Genetic Modulation of Lifespan: Dynamic Effects, Sex Differences, and Body Weight Trade-offs
Genetic Modulation of Lifespan: Dynamic Effects, Sex Differences, and Body Weight Trade-offs Open
The dynamics of lifespan are shaped by DNA variants that exert effects at different ages. We have mapped genetic loci that modulate age-specific mortality using an actuarial approach. We started with an initial population of 6,438 pubescen…
View article: Transcriptomic Hallmarks of Mortality Reveal Universal and Specific Mechanisms of Aging, Chronic Disease, and Rejuvenation
Transcriptomic Hallmarks of Mortality Reveal Universal and Specific Mechanisms of Aging, Chronic Disease, and Rejuvenation Open
SUMMARY Health is strongly affected by aging and lifespan-modulating interventions, but the molecular mechanisms of mortality regulation remain unclear. Here, we conducted an RNA-seq analysis of mice subjected to 20 compound treatments in …
View article: Targeting mitochondrial dysfunction using methylene blue or mitoquinone to improve skeletal aging
Targeting mitochondrial dysfunction using methylene blue or mitoquinone to improve skeletal aging Open
Methylene blue (MB) is a well-established antioxidant that has been shown to improve mitochondrial function in both in vitro and in vivo settings. Mitoquinone (MitoQ) is a selective antioxidant that specifically targets mitochondria and ef…
View article: Contributions of mouse genetic strain background to age-related phenotypes in physically active HET3 mice
Contributions of mouse genetic strain background to age-related phenotypes in physically active HET3 mice Open
We assessed aging hallmarks in skin, muscle, and adipose in the genetically diverse HET3 mouse, and generated a broad dataset comparing these to individual animal diagnostic SNPs from the 4 founding inbred strains of the HET3 line. For mid…
View article: Featured Cover
Featured Cover Open
Cover legend: The cover image is based on the Research Article Age‐related changes to adipose tissue and peripheral neuropathy in genetically diverse HET3 mice differ by sex and are not mitigated by rapamycin longevity treatment by Jake W.…
View article: Age‐related changes to adipose tissue and peripheral neuropathy in genetically diverse <scp>HET3</scp> mice differ by sex and are not mitigated by rapamycin longevity treatment
Age‐related changes to adipose tissue and peripheral neuropathy in genetically diverse <span>HET3</span> mice differ by sex and are not mitigated by rapamycin longevity treatment Open
Neural communication between the brain and adipose tissues regulates energy expenditure and metabolism through modulation of adipose tissue functions. We have recently demonstrated that under pathophysiological conditions (obesity, diabete…
View article: Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice
Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice Open
Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)‐1,3‐butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2‐activating botanical mixture PB125, sulindac, syringaresinol, or the com…
View article: Sex- and age-dependent genetics of longevity in a heterogeneous mouse population
Sex- and age-dependent genetics of longevity in a heterogeneous mouse population Open
DNA variants that modulate life span provide insight into determinants of health, disease, and aging. Through analyses in the UM-HET3 mice of the Interventions Testing Program (ITP), we detected a sex-independent quantitative trait locus (…
View article: Rapamycin/metformin co‐treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice
Rapamycin/metformin co‐treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice Open
Rapamycin treatment has positive and negative effects on progression of type 2 diabetes (T2D) in a recombinant inbred polygenic mouse model, male NONcNZO10/LtJ (NcZ10). Here, we show that combination treatment with metformin ameliorates ne…
View article: 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
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 Open
In genetically heterogeneous mice produced by the CByB6F1 x C3D2F1 cross, the “non‐feminizing” estrogen, 17‐α‐estradiol (17aE2), extended median male lifespan by 19% ( p < 0.0001, log‐rank test) and 11% ( p = 0.007) when fed at 14.4 ppm st…
View article: Neuroendocrine inhibition of glucose production and resistance to cancer in dwarf mice
Neuroendocrine inhibition of glucose production and resistance to cancer in dwarf mice Open
Pit1 null (Snell dwarf) and Proph1 null (Ames dwarf) mutant mice lack GH, PRL and TSH. Snell and Ames dwarf mice also exhibit reduced IGF-I, resistance to cancer and a longer lifespan than control mice. Endogenous glucose production during…
View article: Rapamycin‐mediated mouse lifespan extension: Late‐life dosage regimes with sex‐specific effects
Rapamycin‐mediated mouse lifespan extension: Late‐life dosage regimes with sex‐specific effects Open
To see if variations in timing of rapamycin (Rapa), administered to middle aged mice starting at 20 months, would lead to different survival outcomes, we compared three dosing regimens. Initiation of Rapa at 42 ppm increased survival signi…
View article: Genetic differences and longevity‐related phenotypes influence lifespan and lifespan variation in a sex‐specific manner in mice
Genetic differences and longevity‐related phenotypes influence lifespan and lifespan variation in a sex‐specific manner in mice Open
Epidemiological studies of human longevity found two interesting features, robust advantage of female lifespan and consistent reduction of lifespan variation. To help understand the genetic aspects of these phenomena, the current study exa…
View article: Canagliflozin extends life span in genetically heterogeneous male but not female mice
Canagliflozin extends life span in genetically heterogeneous male but not female mice Open
Canagliflozin (Cana) is an inhibitor of the sodium glucose transporter 2 (SGLT2), and is thought to act by blocking renal reuptake and intestinal absorption of glucose. Cana is FDA-approved for treatment of diabetes, and affords protection…
View article: Canagliflozin Extends Lifespan in Genetically Heterogeneous Male But Not Female Mice
Canagliflozin Extends Lifespan in Genetically Heterogeneous Male But Not Female Mice Open
Canagliflozin (Cana) is an inhibitor of the sodium glucose transporter 2 (SGLT2), and is thought to act by blocking renal reuptake and intestinal absorption of glucose. Cana is FDA-approved for treatment of diabetes, and affords protection…
View article: Differential Effects of Rapamycin on Glucose Metabolism in Nine Inbred Strains
Differential Effects of Rapamycin on Glucose Metabolism in Nine Inbred Strains Open
Studies in mice suggest that rapamycin has a negative impact on glucose homeostasis by inducing insulin resistance. However, results have been inconsistent and difficult to assess because the strains, methods of treatment, and analysis var…
View article: Glycine supplementation extends lifespan of male and female mice
Glycine supplementation extends lifespan of male and female mice Open
Diets low in methionine extend lifespan of rodents, though through unknown mechanisms. Glycine can mitigate methionine toxicity, and a small prior study has suggested that supplemental glycine could extend lifespan of Fischer 344 rats. We …
View article: Acarbose improves health and lifespan in aging HET3 mice
Acarbose improves health and lifespan in aging HET3 mice Open
To follow‐up on our previous report that acarbose (ACA), a drug that blocks postprandial glucose spikes, increases mouse lifespan, we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneou…
View article: Additional file 1 of Changes in the gut microbiome and fermentation products concurrent with enhanced longevity in acarbose-treated mice
Additional file 1 of Changes in the gut microbiome and fermentation products concurrent with enhanced longevity in acarbose-treated mice Open
Summary statistics, associations with design parameters and metabolites, and inferred taxonomic identity of common bacterial OTUs. Table includes all OTUs with mean relative abundance greater than 0.01% and found in greater than 5% of samp…
View article: THE NIA INTERVENTIONS TESTING PROGRAM: AN UPDATE
THE NIA INTERVENTIONS TESTING PROGRAM: AN UPDATE Open
The NIA Interventions Testing Program is a preclinical, multi-site translational research program to evaluate agents hypothesized to extend mouse lifespan by retarding aging or postponing late life diseases. Interventions proposed by scien…
View article: Rapamycin treatment benefits glucose metabolism in mouse models of type 2 diabetes
Rapamycin treatment benefits glucose metabolism in mouse models of type 2 diabetes Open
Numerous studies suggest that rapamycin treatment promotes insulin resistance, implying that rapamycin could have negative effects on patients with, or at risk for, type 2 diabetes (T2D). New evidence, however, indicates that rapamycin tre…
View article: Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer
Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer Open
The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are publi…
View article: Reduced <i>in vivo</i> hepatic proteome replacement rates but not cell proliferation rates predict maximum lifespan extension in mice
Reduced <i>in vivo</i> hepatic proteome replacement rates but not cell proliferation rates predict maximum lifespan extension in mice Open
Combating the social and economic consequences of a growing elderly population will require the identification of interventions that slow the development of age-related diseases. Preserved cellular homeostasis and delayed aging have been p…