Trillions of microorganisms
live in our gut, mouth, skin and
body, collectively comprising
our human microbiome.
bacterial infection acquired after antibiotics, often in hospitals, that kills more than 15,000 people a year. In a trial
published in The New England Journal of Medicine, 94 percent of C. diff patients who received FM T recovered. “It’s the
closest thing to a miracle I’ve seen in medicine,” said gastroenterologist Zain Kassam, interviewed in a New Yorker
piece called “The Excrement Experiment” last December.
Can managing gut health and one’s microbiome prevent
disease and lengthen life? Research has connected changes in
gut bacteria with cancer, diabetes, inflammatory bowel and
age-related disease. In a study headed by Heinrich Jasper, professor and chief science officer at the Buck, scientists altered
the gut bacteria of fruit flies, which significantly increased their
life span. The bacterial load in fly intestines had increased dramatically with age, causing an inflammatory condition and
production of free radicals that can lead to a precancerous state.
“Our study explores age-related changes in the gut that include
increased oxidative stress, inflammation, impaired efficiency of
the immune response, and the overproliferation of stem cells,”
he says. Increasing the expression of PGRP-SC, the molecules
that regulate the immune response to bacteria in the intestinal epithelium (a response that can be mimicked by drugs),
restored microbial balance and halted overproiferation of stem
cells, increasing life span. The study supports the idea that the
right microbiome balance is vital to wellness and longevity.
It’s not yet known whether diet can significantly
strengthen the microbiome, Jasper adds. But probiotic-
rich foods like kefir, yogurt, kimchi, kombucha and miso
may help keep the gut in balance.
The immunosuppressant drug Rapamycin also shows promise as a longevity-extending agent. The Buck’s Kennedy is
conducting research on cell-signaling pathways, in particular
the m TOR pathway, which senses cellular nutrients, oxygen and energy levels and tells cells whether to grow, divide
or stop. When cells are constantly active, he explains, they
can spew toxic free radicals. Kennedy hopes to determine
whether pathways like m TOR can be regulated to prevent or
treat aging-related disease. Studies of mice show Rapamycin
has a “robust” effect on life span, extending it by 30 percent
even in rodents of advanced age.
Rapamycin is already in use for human organ transplant patients,
but it has considerable side effects, and Kennedy emphasizes no one
is talking about prescribing it for longevity just yet. But the implications for aging humans are intriguing. In one groundbreaking study, a
group of healthy people 65 and older took a derivative of Rapamycin for
six weeks, followed by flu vaccine two weeks after stopping the drug.
“Rapamycin was tolerated by healthy older people and it improved their
reaction to the influenza vaccine,” Kennedy says. But it can also “
suppress the immune system and effect insulin resistance,” he adds. “We
need a new derivative of this drug.” Still, the study “certainly sets the
stage for future clinical trials of drugs that show promise to (one day)
improve the health of older adults.”
The importance of protein homeostasis — an organism’s ability to maintain the proper structure and balance of its proteins — is another hopeful
area of research. In a Buck Institute study, Gordon Lithgow, Ph.D., found
that Thioflavin T (aka Th T or Basic Yellow 1), a dye used in labs to detect
damaged proteins in Alzheimer’s, extended life span in healthy nematode
worms by more than 50 percent and slowed Alzheimer’s in worms bred to
mimic aspects of the disease.
“A protein is a long molecule that has to take a certain shape to function,” Lithgow says. “Most proteins take the right shape and do their jobs.
But as we age, a lot of proteins take a different shape — they don’t fold correctly or they unfold and do damage. They can also stick to each other,
becoming insoluble,” one of the hallmarks of Parkinson’s disease.
Since many degenerative diseases are linked to breakdown in protein
homeostasis, it’s encouraging that ThT supports homeostasis instead
— especially given that genetic studies show it contributes greatly to
longevity in complex animals. “We have been looking for compounds that
slow aging for more than 10 years, and ThT is the best we have seen so
far,” Lithgow says. It also “slows the clumping of toxic protein fragments,”
which may explain another way it can extend life span.
Other research is highlighting the life-extending powers of lithium,
a drug normally prescribed for bipolar disorder. “We stumbled across
it when working with worms,” Lithgow says. While lithium is toxic in
high concentrations, there’s a “sweet spot” where it’s beneficial. Buck
Institute scientist Julie Andersen, Ph.D., an expert in Parkinson’s, has
also observed positive effects of low-dosage lithium in older mice having
a Parkinson’s mutation, suggesting more research is warranted to see if
it can help humans with the disease.
“I think aging research is at a tipping point,” Lithgow says. “In the labs
we are seeing unbelievable changes in organisms — age-related diseases are
disappearing, life spans are extending, and we are starting to understand
the mechanisms (of aging), so there’s lots of promising stuff. Translating
this to humans is a whole different story and takes years. But we should be
excited about it as a society.” M