Publications by authors named "Adam B Salmon"

With the development of the technology to generate transgenic and knockout mice in the 1990s, investigators had a powerful tool to directly test the impact of altering a specific gene on a biological process or disease. Over the past three decades, investigators have used transgenic and knockout mouse models, which have altered expression of antioxidant genes, to test the role of oxidative stress/damage in aging and age-related diseases. In this comprehensive review, we describe the studies using transgenic and knockout mouse models to test the role of oxidative stress/damage in aging (longevity) and three age-related diseases, e.

View Article and Find Full Text PDF
Article Synopsis
  • Mitochondria are essential for brain health, influencing energy production, inflammation, and hormone synthesis, and their dysfunction is connected to neurodegenerative diseases like Alzheimer's and Parkinson's.
  • Research on aging baboons revealed a decline in the activity of mitochondrial electron transport chain (ETC) complexes in the prefrontal cortex, mainly tied to alterations in individual complex functions rather than overall mitochondrial numbers.
  • Female baboons maintained mitochondrial function better with age compared to males, who exhibited significant ETC activity loss and had correlations between walking speed and respiration linked to higher ETC complexes, pointing to possible reasons behind sex differences in brain resilience as they age.
View Article and Find Full Text PDF

17α-estradiol extends healthspan and lifespan in male mice without significant feminization or deleterious effects on reproductive function, making it a candidate for human translation. However, studies in animal models that more accurately replicate human physiology are necessary to establish 17α-estradiol dosing standards for clinical trials. This study evaluated the tolerability of 17α-estradiol treatment in the common marmoset over a short treatment duration.

View Article and Find Full Text PDF

Objective: Pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) can attenuate experimental osteoarthritis (OA) in young, male preclinical models. However, the potential of mTOR inhibition as a therapeutic mechanism for OA remains unknown. The goal of this study was to determine if mTOR-inhibition by oral rapamycin can modify OA pathology in the common marmoset, a translational model of age-associated OA.

View Article and Find Full Text PDF

Genetically heterogeneous UM-HET3 mice born in 2020 were used to test possible lifespan effects of alpha-ketoglutarate (AKG), 2,4-dinitrophenol (DNP), hydralazine (HYD), nebivolol (NEBI), 16α-hydroxyestriol (OH_Est), and sodium thiosulfate (THIO), and to evaluate the effects of canagliflozin (Cana) when started at 16 months of age. OH_Est produced a 15% increase (p = 0.0001) in median lifespan in males but led to a significant (7%) decline in female lifespan.

View Article and Find Full Text PDF

We previously demonstrated in baboons that maternal undernutrition (MUN), achieved by 70 % of control nutrition, impairs fetal liver function, but long-term changes associated with aging in this model remain unexplored. Here, we assessed clinical phenotypes of liver function, mitochondrial bioenergetics, and protein abundance in adult male and female baboons exposed to MUN during pregnancy and lactation and their control counterparts. Plasma liver enzymes were assessed enzymatically.

View Article and Find Full Text PDF

Biological resilience, broadly defined as the ability to recover from an acute challenge and return to homeostasis, is of growing importance to the biology of aging. At the cellular level, there is variability across tissue types in resilience and these differences are likely to contribute to tissue aging rate disparities. However, there are challenges in addressing these cell-type differences at regional, tissue, and subject level.

View Article and Find Full Text PDF

Age-related osteoarthritis (OA) is a degenerative joint disease characterized by pathological changes in nearly every intra- and peri-articular tissue that contributes to disability in older adults. Studying the etiology of age-related OA in humans is difficult due to an unpredictable onset and insidious nature. A barrier in developing OA modifying therapies is the lack of translational models that replicate human joint anatomy and age-related OA progression.

View Article and Find Full Text PDF

Biological resilience, broadly defined as ability to recover from acute challenge and return to homeostasis, is of growing importance to the biology of aging. At the cellular level, there is variability across tissue types in resilience and these differences likely to contribute to tissue aging rate disparities. However, there are challenges in addressing these cell-type differences at regional, tissue and subject level.

View Article and Find Full Text PDF

Methionine restriction (MR) has been shown to affect mitochondrial function including altering oxygen consumption, reactive oxygen species (ROS) generation, Complex expression, and oxidative damage. The sulfur-containing amino acid methionine can become oxidized forming methionine sulfoxide which can lead to changes in protein function and signaling. Methionine sulfoxide reductases are endogenous enzymes capable of reducing methionine sulfoxide, with Methionine sulfoxide reductase A (MsrA) being ubiquitously expressed in mammals.

View Article and Find Full Text PDF

Myogenous temporomandibular disorders is associated with an increased responsiveness of nerves innervating the masseter (MM), temporal (TM), and lateral pterygoid muscles (LPM). This study aimed to examine sensory nerve types innervating MM, TM and LPM of adult non-human primate-common marmosets. Sensory nerves were localized in specific regions of these muscles.

View Article and Find Full Text PDF

Researchers and veterinarians often use hematology and clinical chemistry to evaluate animal health. These biomarkers are relatively easy to obtain, and understanding how they change across healthy aging is critical to clinical care and diagnostics for these animals. We aimed to evaluate how clinical biomarkers from a chemistry profile and complete blood count (CBC) change with age in common marmosets (Callithrix jacchus).

View Article and Find Full Text PDF
Article Synopsis
  • Oral health is really important for older people, but we don't understand it well because studying it with animal models is tricky.
  • This study looked at marmosets (a type of small monkey) to understand how oral health changes as they age, comparing young, middle-aged, and older groups.
  • The results showed that older marmosets had more tooth problems and certain bacteria in their mouths, suggesting that studying these monkeys can help us learn about the effects of aging on human oral health.
View Article and Find Full Text PDF

Using DNA methylation profiles ( = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors.

View Article and Find Full Text PDF

Age and sex have a profound effect on cytosine methylation levels in humans and many other species. Here we analyzed DNA methylation profiles of 2400 tissues derived from 37 primate species including 11 haplorhine species (baboons, marmosets, vervets, rhesus macaque, chimpanzees, gorillas, orangutan, humans) and 26 strepsirrhine species (suborders Lemuriformes and Lorisiformes). From these we present here, pan-primate epigenetic clocks which are highly accurate for all primates including humans (age correlation R = 0.

View Article and Find Full Text PDF

Methionine restriction (MR) extends lifespan in various model organisms, and understanding the molecular effectors of MR could expand the repertoire of tools targeting the aging process. Here, we address to what extent the biochemical pathway responsible for redox metabolism of methionine plays in regulating the effects of MR on lifespan and health span. Aerobic organisms have evolved methionine sulfoxide reductases to counter the oxidation of the thioether group contained in the essential amino acid methionine.

View Article and Find Full Text PDF

A growing number of pharmaceutical and small molecule interventions are reported to extend the lifespan of laboratory animals including Caenorhabditis, Drosophila, and mouse. However, the degree to which these pro-longevity interventions are conserved across species is unclear. Here, we took two approaches to ask the question: to what extent do longevity intervention studies in Caenorhabditis and Drosophila recapitulate effects on mouse lifespan? The first approach analyzes all published reports on longevity in the literature collated by the DrugAge database, and the second approach focused on results designed for reproducibility as reported from the NIA-supported Interventions Testing Program (ITP) and the Caenorhabditis Interventions Testing Program (CITP).

View Article and Find Full Text PDF

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 combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice receiving both drugs was neither higher nor lower than that seen previously in Rapa only, perhaps reflecting the limited survival benefits seen in prior cohorts of females receiving Aca alone.

View Article and Find Full Text PDF
Article Synopsis
  • - Canagliflozin (Cana) increases lifespan by 14% in male mice but doesn’t affect female mice, according to a study involving 7-month-old genetically diverse male mice.
  • - A histopathological analysis of 22-month-old mice showed that Cana reduced the severity of various age-related diseases in male mice, including heart disease, kidney issues, and certain tumors, but also provided protection against pancreas atrophy in both sexes.
  • - The findings suggest that Canagliflozin may slow down the aging process and could have potential benefits for other health issues associated with aging, warranting further research.
View Article and Find Full Text PDF

We conducted a dose-response study of dexamethasone to investigate an optimal dexamethasone suppression test for common marmosets. Twelve marmosets received 0.1, 0.

View Article and Find Full Text PDF

Previously, we showed that extracellular matrices (ECMs), produced ex vivo by various types of stromal cells, direct bone marrow mesenchymal stem cells (BM-MSCs) in a tissue-specific manner and recapitulate physiologic changes characteristic of the aging microenvironment. In particular, BM-MSCs obtained from elderly donors and cultured on ECM produced by young BM stromal cells showed improved quantity, quality and osteogenic differentiation. In the present study, we searched for matrix components that are required for a functional BM-MSC niche by comparing ECMs produced by BM stromal cells from "young" (≤25 y/o) versus "elderly" (≥60 y/o) donors.

View Article and Find Full Text PDF
Article Synopsis
  • - A study examined the effects of a drug combination (rapamycin, acarbose, and phenylbutyrate) on aging in mice, suggesting that targeting multiple biological pathways may be beneficial for healthy aging.
  • - Middle-aged mice fed the drug cocktail experienced improvements in body fat, cognition, strength, endurance, and reduced age-related issues compared to those given single drugs or no treatment.
  • - The results indicate that combining these three drugs may provide a greater protective effect against aging-related damage in organs like the heart and liver, compared to using each drug alone.
View Article and Find Full Text PDF

Physical resilience, the capacity to respond to and recover from a stressful event, declines with advancing age. Individuals respond differently to physical stressors across their lifespans. While the biological underpinnings of resilience remain unclear, a plausible determinant is the capacity of an individual's cellular and molecular levels to return to homeostasis after a physical challenge.

View Article and Find Full Text PDF

Methionine restriction (MR) extends lifespan and improves several markers of health in rodents. However, the proximate mechanisms of MR on these physiological benefits have not been fully elucidated. The essential amino acid methionine plays numerous biological roles and limiting its availability in the diet directly modulates methionine metabolism.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session1hvjefqu3e3c3h5uhpevaaq57l402pdq): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once