What can we learn from centenarians who defy the odds of early death?

As we age, the microbiome undergoes significant changes that can impact our health and well-being.

In a recent study published in the journal PLOS Biology, a study highlighted the latest breakthroughs in comprehending the correlation between the microbiome and aging as well as related health conditions.

Several illnesses in developed nations are primarily linked to the aging process. Microorganisms inhabit various regions both inside and outside the human body, with the largest number residing in the gastrointestinal (GI) tract.

Previous studies have emphasized the critical role that gut microbiota plays in maintaining good health and preventing diseases.

The impact of the microbiome on the aging process and the potential to manipulate it to promote healthy aging are not yet well understood. The authors of the study discuss the emerging evidence on the role of the microbiome in aging and age-related ailments.

Centenarians have a higher level of bacterial diversity compared to younger individuals and possess a greater amount of Clostridium, Parabacteroides, and Alistipes. Additionally, numerous microbial metabolites are heightened in centenarians. The frailty of an individual has been associated with differences in the gut microbiome between individuals. Less frail adults have a greater gut microbial diversity than older frail adults.

While the causal relationship between microbiota and frailty remains unclear, aging leads to a weakened immune system that results in the expansion of formerly suppressed microbes.

Studies conducted on germ-free (GF) animal models have supported the notion that the microbiome plays a causal role in determining the lifespan of hosts. Studies of model systems have suggested that exposure to the microbiome during early life can enhance lifespan. Evidence also suggests that bacterial colonization during the embryonic development of Drosophila melanogaster can increase lifespan.

However, these findings conflict with research conducted on GF mice, rats, or Caenorhabditis elegans that have outlived conventionally raised control animals. Thus, the harmful effects of microbiota in later life may outweigh the potential benefits of colonization in early life.

The microbiome can shorten the lifespan of older animals. For instance, the accumulation of Escherichia coli in the gastrointestinal (GI) tract of Caenorhabditis elegans can lead to age-related death.

A study revealed that mid-aged (9.5 weeks) killifish treated with antibiotics had a longer lifespan than untreated killifish. Interestingly, mid-aged groups that were inoculated with microbiota from a six-week-old killifish had an extended lifespan.

Furthermore, research conducted on mouse models of progeria has shown that lifespan can be extended through microbiome-based interventions.

The prevalence of cancer increases with age, with less than 25 cases per 100,000 individuals under the age of 20 and over 1,000 cases per 100,000 people over 60. This trend is also observed in prostate, colorectal, and breast cancers.

A comparison between malignant tumors in colorectal cancer and adjacent non-malignant mucosa showed a significant enrichment of Fusobacterium nucleatum. Mice studies have provided evidence of the causal role of this bacterium in colon cancer, where it activates the expression of oncogenic and pro-inflammatory genes and pathways promoting myeloid cell infiltration.

In addition, fecal microbiota transplantation (FMT) from immunotherapy-responsive melanoma patients into others reduced tumor size. Anti-cancer drugs can also be broken down by the microbiome into substances with more or less activity.

A study has found several ways in which the microbiome can affect the phenotypes of type 2 diabetes or obesity. The microbiome helps digest parts of food that would be hard to break down on their own. This makes it easier to get calories from food.

It can also change how much energy the host uses by changing how its enzymes work and how its genes are expressed. The majority of Parkinson’s disease cases (>95%) occur in adults older than 50, and emerging evidence implicates the GI tract in this condition.

Research on mice showed how the gut microbiome and brain talk to each other to affect the development of Parkinson’s disease. In a mouse model of Parkinson’s disease with an excess of α-synuclein, researchers found evidence of a changed microbiome (ASO model).

Motor impairment and brain pathology are both worsened in GF ASO mice when they are colonized with the gut microbiota of afflicted mice/humans.

In terms of longevity, age-related illnesses, and frailty, aging differs between men and women. The majority of age-related illnesses exhibit sexual dimorphism; females are more likely to develop and survive cancer, and the occurrence of numerous non-reproductive tumors is strongly sex-biased.

Also, although type 2 diabetes risk is similar for both sexes, females are more likely than men to be obese.

Parkinson’s disease is more common in men, but it is more severe in women. Sex and the human microbiota are connected, according to recent research. According to preliminary findings, sex hormones are mediating this link.

GF mice have different amounts of sex hormones than mice bred traditionally. Moreover, the makeup and diversity of the gut microbiota are related to the levels of sex hormones in circulation.

The authors provided a summary of the current evidence on the role of the microbiome in aging and related diseases.

In future research on aging and age-related diseases, it is crucial to focus on the role of the microbiome by utilizing germ-free (GF) models, microbiome profiling, and controlling for associated variables.

Furthermore, it is essential to determine how sex impacts the microbiome and the downstream outcomes of age-related diseases. Overall, this emerging interdisciplinary research field has the potential to address pressing questions regarding host-microbiome interactions throughout the lifespan.

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