Talk to Me-Interplay between Mitochondria and Microbiota in Aging

Abstract

The existence of mitochondria in eukaryotic host cells as a remnant of former microbial organisms has been widely accepted, as has their fundamental role in several diseases and physiological aging. In recent years, it has become clear that the health, aging, and life span of multicellular hosts are also highly dependent on the still-residing microbiota, e.g., those within the intestinal system. Due to the common evolutionary origin of mitochondria and these microbial commensals, it is intriguing to investigate if there might be a crosstalk based on preserved common properties. In the light of rising knowledge on the gut-brain axis, such crosstalk might severely affect brain homeostasis in aging, as neuronal tissue has a high energy demand and low tolerance for according functional decline. In this review, we summarize what is known about the impact of both mitochondria and the microbiome on the host's aging process and what is known about the aging of both entities. For a long time, bacteria were assumed to be immortal; however, recent evidence indicates their aging and similar observations have been made for mitochondria. Finally, we present pathways by which mitochondria are affected by microbiota and give information about therapeutic anti-aging approaches that are based on current knowledge.

Keywords: archaea; bacteria; fission; fusion; organelle; respiratory chain; virus.

Figure 1

Aging in multi-cellular organisms and bacterial cells. Left: using germline cells, multi-cellular organisms such as mice allow their offspring to start with a non-exhausted cell pool while the parental animals accumulate dysfunctional cells with age, leading to diseased states, frailty, and finally death. Right: in bacterial cell division, morphological and functional asymmetry occurs. The schematic diagram of C. crescentus shows that during its life cycle, it gives rise to two morphologically different daughter cells: the stalked cell remains attached to the substrate, while the swarmer cell is motile due to its flagellum. E. coli and many other bacteria seemingly divide symmetrically. However, probabilities of the two cells rising from division, designated young and old pole cells, are divergent (image created by BioRender).

Figure 2

Affected mitochondrial pathways. Viral (A) as well as bacterial (B) commensals or pathogens can have an influence on a variety of molecular pathways that are important for maintenance and function of the host’s mitochondria. The impact of the microbiota might be directly or via the host’s own transcriptional/translational machinery, such as for PGC-1α (with subsequent activation of NRF1 and TFAM) or PPARγ (orchestrating lipid metabolism, e.g., β-oxidation) (the image was created by using BioRender). Drp1: dynamin-related protein 1; Fis1: mitochondrial fission protein 1; HDAC: histone deacetylas; Mff: mitochondrial fission factor; Mfn1/2: mitofusin 1/2; mPTP: mitochondrial permeability transit pore; NRF1: nuclear respiratory factor 1; Opa1: optic atrophy-1; TFAM: mitochondrial transcription factor A.

Figure 3

Changes in microbiota and their metabolites during aging and their protective role or their involvement in the pathophysiology of diseases. Effects of interventions such as prebiotics, probiotics, polyphenols, and Mediterranean diet on metabolites of microbiota are indicated (arrows indicate direction of change (increase or decrease); ?: unknown; the image was created by using BioRender).