117-year-old man dies! Is longevity determined by genes or intestinal flora?

BEIJING, Aug. 21 (Xinhua) -- Maria Branyas Moreira, who holds the title of the world's oldest living person, died in a Spanish nursing home on August 19 at the age of 117 years and 168 days, the Guinness World Records website said on the 20th.

What determines longevity?

Recently, the English version of Science China: Life Sciences published a review article by Jin Feng, a researcher at the Institute of Psychology, Chinese Academy of Sciences. The article reviewed the research on the relationship between intestinal microorganisms and longevity in recent years, and revised the long-standing misunderstanding of longevity, which believed that longevity is a destiny and is innate in the family. The research revealed that anyone can achieve healthy longevity through adjusting their intestinal microbiota, rather than simply a number of years.

People have always believed that health and longevity are mainly affected by genetic factors, and have been committed to finding genes related to longevity. Studies in recent years have shown that the impact of genes on human health and longevity is actually relatively small, only 10%-15%. In addition to being affected by genetic factors, health and longevity are more affected by environmental factors, among which intestinal flora plays an important role. A large number of studies have found that the intestinal flora of healthy centenarians is significantly different from that of the elderly and unhealthy centenarians. Compared with other mammals, bats and naked mole rats, two super long-lived mammals, also have significantly different intestinal flora.

The results of sterile culture, fecal microbiota transplantation, and probiotic supplementation further provide direct evidence that the intestinal flora affects the health and longevity of the host. The lifespan of sterile cultured fruit flies and Caenorhabditis elegans increased significantly; transplanting fecal microbiota from young mice to old mice significantly extended the healthy lifespan of old mice, while the opposite transplantation shortened the lifespan of young mice; supplementation with specific probiotics (mainly specific lactobacilli and bifidobacteria) can significantly extend the healthy lifespan of fruit flies, Caenorhabditis elegans, and mice. A large number of randomized controlled trials have shown that supplementation with probiotics can promote healthy aging in the elderly and delay the occurrence and development of aging-related diseases.

Gut flora promotes health and longevity mainly through five signaling pathways. First, by producing abundant tryptophan metabolites, indole derivatives, short-chain fatty acids and bile acids, gut flora can enhance the integrity of the intestinal mucosal barrier. Second, by secreting a large amount of kynurenine, short-chain fatty acids and bile acids, gut flora promotes the proliferation of anti-inflammatory immune cells, thereby reducing inflammatory aging. Third, gut flora and the short-chain fatty acids they release can improve nutrient sensing signaling pathways, including the rapamycin target pathway, the insulin/insulin-like growth factor pathway, the adenosine phosphate-activated protein kinase pathway and the deacetylase pathway. Fourth, by producing abundant capsular isopolysaccharide acid, betaine, methionine, cysteine ​​and urolithin A, gut flora can optimize mitochondrial function. Fifth, by releasing abundant tryptophan metabolites, indole derivatives, short-chain fatty acids, bile acids and neurotransmitters, gut flora can effectively improve cardiovascular and cerebrovascular diseases, cancer, and aging-related diseases such as Alzheimer's disease and Parkinson's disease.

A deeper understanding of the effects of intestinal flora on health and longevity and its mechanisms will help to promote human health and longevity and prevent aging-related diseases in the future by targeting the regulation of intestinal flora, provided that specific strains that promote health and longevity are identified. Although a large number of studies have analyzed the intestinal flora structure of centenarians, no specific longevity bacteria have been screened out so far. The main reason for this is that there are a variety of mixed factors that affect the flora structure of centenarians, including genetics, lifestyle, disease conditions, and drug use. Even so, a large number of studies have consistently found that compared with the elderly and unhealthy centenarians, the Proteobacteria and Prevotella genera in the intestines of healthy centenarians are significantly increased. Proteobacteria and Prevotella are generally considered to be conditional pathogens and are associated with a variety of inflammatory diseases in humans. However, surprisingly, centenarians can remain healthy with abundant Proteobacteria and Prevotella, which seems to indicate a possible symbiotic relationship between them, which can also be explained as humans should always live between a mild pro-inflammatory and anti-inflammatory balance to achieve the maximum immune effect.

Similar symbiotic relationships also exist among the Hadza people of Tanzania, as well as bats and naked mole rats. Understanding the symbiotic mechanisms of centenarians with Proteobacteria and Prevotella may provide some reference for coping with aging-related diseases and promoting health and longevity. The symbiosis between Proteobacteria and Prevotella and centenarians may originate from early life contact. Early life contact with conditional pathogens or even specific pathogens can reduce the immune response to them in adulthood and thus produce immune tolerance. Soil, plants, water sources and animals in nature are the main sources of Proteobacteria and Prevotella. Existing studies have indeed found that centenarians are usually born and live in rural areas rich in soil, plants, water sources and animals for a long time.

In addition to early exposure to Proteobacteria and Prevotella, a healthy lifestyle can also promote health and longevity by affecting the intestinal flora. Centenarians usually have a variety of healthy lifestyles, such as consuming more healthy and organic foods, exercising properly, having better sleep quality and good social activities. These healthy lifestyles have been found to effectively increase the content of short-chain fatty acids derived from intestinal flora, and short-chain fatty acids can promote health and longevity by widely participating in the regulation of the "longevity signaling pathway" mentioned earlier.

Figure 1 Healthy intestinal microbes protect humans and significantly reduce the risk of cognitive impairment, Parkinson's disease and other senile degenerative diseases, and cancer

The most positive reminder from these studies is that longevity genes are not a superior destiny, and anyone has the opportunity to actively change their life span. Whether it is natural and healthy longevity or relying on medicine to struggle for longevity, intestinal flora and healthy food play a more important role.

The first author of the article is Associate Professor Luo Jia from the School of Psychology at Sichuan Normal University, the second author is Researcher Liang Shan from the Gut-Brain Psychology Laboratory, and the corresponding author is Researcher Jin Feng from the Institute of Psychology, Chinese Academy of Sciences.

For more details, please read the full article

Gut microbiota and healthy longevity. Science China Life Sciences.

DOI:10.1007/s11427-023-2595-5