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Boyajian et al. Microbiome Res Rep 2024;3:29 https://dx.doi.org/10.20517/mrr.2024.05 Page 3 of 35

Figure 1. A comparison of gut microbiota, intestinal epithelium, and systemic health in healthy versus obese or aged individuals. A
balanced gut microbiome maintains host health homeostasis, while a dysbiotic gut leads to an impaired intestinal barrier and harmful
systemic consequences, as evident in obesity and aging. The downstream effects of gut dysbiosis, such as inflammation, adipose tissue
dysfunction, and muscular atrophy, promote obese and aging phenotypes. TJs: Tight junctions; GBA: gut-brain axis.

defined as a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat
promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic,
[3]
biomechanical, and psychosocial health consequences” by the Obesity Medicine Association (OMA) . Poor
dietary habits and a sedentary lifestyle are also leading factors behind the pathogenesis and progression of
obesity.

HUMAN AGING: HALLMARKS AND IMPLICATIONS
Aging is a general biological phenomenon that affects all human beings and is characterized by a
progressive loss of physiological integrity, leading to functional decline and increased risk of chronic
[5]
ailments and death . The population of older persons is one of the fastest-growing age groups, representing
10% of the global population in 2022 and expected to reach 16% by 2050, exceeding more than twice the
number of children under the age of five and approximately the same as the number of children under the
age of twelve . Although aging is a natural and inevitable process, accelerated aging (i.e., when biological
[6]
age exceeds chronological age) is a primary risk factor for chronic illness and mortality . According to a
[7]
recent study investigating US and UK populations, accelerated aging mediates the link between unhealthy
lifestyles (i.e., physical inactivity, unhealthy BMI, unhealthy diet, smoking or drinking) and adverse health
outcomes, likely via inflammation or immunity. In contrast, healthy aging is defined as developing and
maintaining the functional ability that enables well-being in older age . The study of geroscience - the
[8]
[9]
intersection of basic aging biology, chronic disease, and health - has gained popularity in the last decade .
Breakthroughs in age-related research have enabled the prevention and improvement of chronic illness
associated with aging, revealing key biomarkers to target aging and chronic disease. However, aging remains
the single largest risk factor for heart attacks, stroke, cancer, and diabetes, among most other chronic