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Page 2 of 11 Xu et al. Microbiome Res Rep 2024;3:13 https://dx.doi.org/10.20517/mrr.2023.68

further involves all tissues and triggers systemic structural breakdown and functional decline. As estimated,
people aged 65 or older accounted for 9.1% of the world’s overall population in 2019, imposing a heavy
[2]
burden on the national economy and healthcare system . Glycation, oxidation, inflammation, and dysbiosis
[3]
have been emphasized for a prominent correlation with aging , which benefits both the elaboration of
aging status and the expansion of the anti-aging drug spectrum. With the deepening of research these years,
the position of gut microbes in aging events has been progressively better described.

Trillions of microbes constitute the broadest human symbiotic microecology, co-operating in the
[5]
[6]
[4]
maintenance of the body’s immune defense , nutrient absorption , and neuroprotection . Technical
advancements in high-throughput sequencing and multi-omics analysis have facilitated the study of
microbiota in individual growth and metabolism, and the role of gut microbes in host aging has been
[7]
increasingly elucidated . Metagenomic sequencing of fecal samples from multiple longevity families
implicated that the diversity of gut microbiota and the abundance of bacterial metabolites in aging
[8]
populations were lower than in younger generations . However, specific adjuncts such as fecal microbiota
transplantation (FMT) or probiotic supplementation could, in turn, help retard aging, or at least
[10]
[9]
enhance the survival quality of the elderly. At this scale, gut microbes can be interpreted as a potential
aging-related biomarker and, through microbiota modulation, hold promise for healthy aging or even aging
reversal.
This mini-review systematically depicts the role of gut microbiota in distinguishing different aging patterns,
and its feasibility in retarding aging or maintaining healthy aging, thus outlining a blueprint for the
application of gut microbes as biomarkers or intervention targets in active health.

BIOLOGICAL OR CLINICAL PERSPECTIVES TO DEFINE AND CHARACTERIZE
DIFFERENT PATTERNS OF AGING
The definition and signatures of aging
Aging can be interpreted as a state of generalized degeneration. The superimposition of genetic and
environmental factors contributes to the complexity of aging, and the intuitive evaluation of clinical aging
by chronological age is no longer applicable. The inconsistency between physical function and age has
become highly pronounced, making biological age a better criterion. Cellular senescence, the initiating link
of systemic aging, first triggers molecular damage, which in turn induces oxidative stress, inflammatory
immunity, nutritional dysregulation, metabolic impairment, and neurodegeneration in the organism, and
[11]
eventually presents signs of aging . On the basis of biological alterations, aging can be classified into
physiological and pathological aging . The latter is often associated with diabetes , cardiovascular
[12]
[13]
[16]
[15]
diseases , cancers , and neuro-degenerative diseases , resulting in poor life quality and, ultimately, a
[14]
shortened lifespan.
It is worth emphasizing that although aging is inevitable, the pursuit of delayed aging or at least healthy
aging is attainable with flexible monitoring and potent interventions. The identification and detection of
aging-related biomarkers are paramount for quantifying the level of physical function and evaluating the
effect of behavioral factors. The ideal aging-related biomarker, as defined by the American Consortium for
Aging Research (AFAR), should enable individualized marking and systematic monitoring of aging, as well
as longitudinal non-invasive follow-up in subjects . The DNAmAge, to determine chronological age based
[17]
on the methylation of deoxyribonucleic acids, and GlycanAge, to track the effects of lifestyle interventions
on aging based on the glycosyl molecules attached to immunoglobulin G, are among the more established
and commercially available biomarkers of aging . Although none have yet been approved for clinical
[18]
application, their accuracy in marking aging is well accepted. Other studies have also focused on the host