The objective of this review was to compare and contrast the physiological and metabolic profiles of rodent white adipose fat pads with white adipose fat depots in humans. Human fat distribution and its metabolic consequences have received extensive attention, but much of what has been tested in translational research has relied heavily on rodents. Unfortunately, the validity of using rodent fat pads as a model of human adiposity has received less attention. There is a surprisingly lack of studies demonstrating an analogous relationship between rodent and human adiposity on obesity-related comorbidities. Therefore, we aimed to compare known similarities and disparities in terms of white adipose tissue (WAT) development and distribution, sexual dimorphism, weight loss, adipokine secretion, and aging. While the literature supports the notion that many similarities exist between rodents and humans, notable differences emerge related to fat deposition and function of WAT. Thus, further research is warranted to more carefully define the strengths and limitations of rodent WAT as a model for humans, with a particular emphasis on comparable fat depots, such as mesenteric fat.

Objective The majority of zoo African elephants exhibit abnormal reproductive cycles, but it is unclear why. Acyclicity has been positively associated with body condition scores. The objective of this study was to measure body composition and examine the relationship between adiposity and cyclicity status, mediated by glucose, insulin, leptin, and inflammation. Methods Body composition was assessed by deuterium dilution in 22 African elephants. Each elephant was weighed and given deuterated water orally (0.05 mL/kg), and blood was collected from the ear prior to and five time after deuterium administration. Glucose, insulin, leptin and pro-inflammatory biomarker concentrations in serum were determined. Results Body fat percentage ranged from 5.24% to 15.97%. Fat adjusted for fat free mass (FFM) and age was not significantly associated with cyclicity status (P=0.332). Age was the strongest predictor of cyclicity status (P=0.040). Fat was correlated with weight (ρ=0.455, P=0.044) and when adjusted for FFM with circulating glucose (ρ=0.520, P=0.022), and showed a trend for association with leptin (unadjusted: ρ=0.384, P=0.095; adjusted for FFM: ρ=0.403, P=0.087). Conclusions Deuterium dilution appears to be an available technique to measure body composition in African elephants. In this sample, fat was not associated with cyclicity status and age may be more important to cyclicity status.

Many captive Asian elephant populations are not self-sustaining, possibly due in part to obesity-related health and reproductive issues. This study investigated relationships between estimated body composition and metabolic function, inflammatory markers, ovarian activity (females only) and physical activity levels in 44 Asian elephants (n=35 females, n=9 males). Deuterium dilution was used to measure total body water from which fat mass (FM) and fat-free mass (FFM) could be derived to estimate body composition. Serum was analyzed for progestagens and estradiol (females only), deuterium, glucose, insulin and amyloid A. Physical activity was assessed by an accelerometer placed on the elephant's front leg for at least 2 days. Relative fat mass (RFM) – the amount of fat relative to body mass – was calculated to take differences in body size between elephants into consideration. Body fat percentage ranged from 2.01% to 24.59%. Male elephants were heavier (P=0.043), with more FFM (P=0.049), but not FM (P>0.999), than females. For all elephants, estimated RFM (r=0.45, P=0.004) was positively correlated with insulin. Distance walked was negatively correlated with age (r=−0.46, P=0.007). When adjusted for FFM and age (P<0.001), non-cycling females had less fat compared with cycling females, such that for every 100 kg increase in FM, the odds of cycling were 3 times higher (P<0.001). More work is needed to determine what an unhealthy amount of fat is for elephants; however, our results suggest higher adiposity may contribute to metabolic perturbations.

Captive elephant populations are not self‐sustaining due to health concerns possibly related to obesity. Categorizing obesity relies on qualitative analyses like body condition scores (BCS). However, elephant indices have not been validated against measured body composition. The objective was to compare BCS systems to body composition determined by deuterium dilution in 28 zoo‐kept Asian elephants. Elephants were weighed and given deuterated water orally (0.05 ml/kg). Blood was collected at ~0, 24, 120, 240, 360, and 480 hr after dosing. Photographs were taken to score the elephant based on four BCS systems (BCSWemmer [0 to 11 scoring], BCSMorfeld [1 to 5 scoring], BCSFernando [0 to 10 scoring], BCSWijeyamohan [1 to 10 scoring]). Based on regression analysis, relative fat ranged from −305 kg to 515 kg, where negative values indicate less and positive values indicate more fat than expected for the elephant's mass in this population. BCSFernando was associated with relative fat (p = .020, R2 = 0.194). Relative fat, adjusted for sex and age in the statistical model, was associated with BCSWemmer (p = .027, R2 = 0.389), BCSFernando (p = .002, R2 = 0.502), and BCSWijeyamohan (p = .011, R2 = 0.426). Inclusion of zoo and familial relatedness resulted in all BCS systems associated with relative fat (p ≤ .015). Only BCSFernando predicted relative fat, unadjusted, suggesting it is the most capable system for practical use. Compared to absolute fat, relative fat may be more biologically relevant as greater fat relative to body mass is more likely to lead to health issues.

Elephants are large-brained, social mammals with a long lifespan. Studies of elephants can provide insight into the aging process, which may be relevant to understanding diseases that affect elderly humans because of their shared characteristics that have arisen through independent evolution. Elephants become sexually mature at 12 to 14 years of age and are known to live into, and past, their 7th decade of life. Because of their relatively long lifespans, elephants may have evolved mechanisms to counter age-associated morbidities, such as cancer and cognitive decline. Elephants rely heavily on their memory, and engage in multiple levels of competitive and collaborative relationships because they live in a fission-fusion system. Female matrilineal relatives and dependent offspring form tight family units led by an older-aged matriarch, who serves as the primary repository for social and ecological knowledge in the herd. Similar to humans, elephants demonstrate a dependence on social bonds, memory, and cognition to navigate their environment, behaviors that might be associated with specializations of brain anatomy. Compared with other mammals, the elephant hippocampus is proportionally smaller, whereas the temporal lobe is disproportionately large and expands laterally. The elephant cerebellum is also relatively enlarged, and the cerebral cortex is highly convoluted with numerous gyral folds, more than in humans. Last, an interesting characteristic unique to elephants is the presence of at least 20 copies of the TP53 tumor suppressor gene. Humans have only a single copy. TP53 encodes for the p53 protein, which is known to orchestrate cellular response to DNA damage. The effects of these multiple copies of TP53 are still being investigated, but it may be to protect elephants against multiple age-related diseases. For these reasons, among others, studies of elephants would be highly informative for aging research. Elephants present an underappreciated opportunity to explore further common principles of aging in a large-brained mammal with extended longevity. Such research can contribute to contextualizing our knowledge of age-associated morbidities in humans.

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While the average human lifespan continues to increase, there is little evidence that this is leading to a contemporaneous increase in “healthy years” experienced by our aging population. Consequently, many scientists focus their research on understanding the process of aging and trialing interventions that can promote healthspan. The 2021 Midwest Aging Consortium (MAC) consensus statement is to develop and further the understanding of aging and age-related disease using the wealth of expertise across universities in the Midwestern United States. This report summarizes the cutting-edge research covered in a virtual symposium held by a consortium of researchers in the Midwestern United States, spanning such topics as senescence biomarkers, serotonin induced DNA protection, immune system development, multi-system impacts of aging, neural decline following severe infection, the unique transcriptional impact of CR of different fat depots, the pivotal role of fasting in calorie restriction, the impact of peroxisome dysfunction, and the influence of early life trauma on health. The symposium speakers presented data from studies conducted in a variety of common laboratory animals as well as less-common species, including C. elegans, Drosophila, mice, rhesus macaques, elephants and humans. The consensus of the symposium speakers is that this consortium highlights the strength of aging research in the Midwestern United States as well as the benefits of a collaborative and diverse approach to geroscience.

This review identifies frequent design and analysis errors in aging and senescence research and discusses best practices in study design, statistical methods, analyses, and interpretation. Recommendations are offered for how to avoid these problems. The following issues are addressed: 1) errors in randomization, 2) errors related to testing within-group instead of between-group differences, 3) failing to account for clustering, 4) failing to consider interference effects, 5) standardizing metrics of effect size, 6) maximum lifespan testing, 7) testing for effects beyond the mean, 8) tests for power and sample size, 9) compression of morbidity versus survival curve-squaring, and 10) other hot topics, including modeling high-dimensional data and complex relationships and assessing model assumptions and biases. We hope that bringing increased awareness of these topics to the scientific community will emphasize the importance of employing sound statistical practices in all aspects of aging and senescence research.