Maria Branyas Morera lived a simple life in a small town in Catalonia, Spain. She loved quality time with family and friends, playing with dogs, reading books, and tending to her garden. She played the piano well into her 110s. And before she died last year at 117, she was the oldest documented person alive.
Her extreme longevity caught the attention of Manel Esteller, a geneticist at the University of Barcelona with a keen interest in longevity. Although Branyas was only one person, her genes, metabolism, and other molecular markers could a shine light on healthy longevity for the rest of us.
Over several years, Esteller and colleagues collected samples of blood, saliva, urine, and stool for a deep dive into her unique biology. Although at the beginning of the study Branyas lived at home with her two daughters—both in their 90s and healthy—she eventually moved into an assisted living home.
Her biology painted a surprising picture of the factors contributing to health in old age. On the one hand, her telomeres—the protective end caps on chromosomes—were exceedingly short, as expected for someone her age. Telomere shortening is usually associated with damaged DNA and a higher risk of cancer. Yet Branyas never had cancer.
Compared to other elderly woman living in the area, Branyas had very low levels of chronic inflammation, which tends to creep up and wreak havoc as we age. And her gut microbiome—a regulator of general health heavily influenced by diet—resembled that of people much younger.
The authors caution that Branyas’s results are for only one exceptional person, and we’d need larger population-sized studies before interpreting them for the general public. In addition, her lifestyle choices likely played a large role in her longevity.
“Our genes are the cards in a poker game. But how we play them is what really matters,” Esteller told Nature.
Super Insights From a Supercentenarian
Aging is an intricate mix of nature and nurture, and it’s notoriously difficult to tease them apart. Studies in worms, flies, and mice have unearthed hallmarks of aging in a web of genes, metabolic signals, stem cell health, inflammation, and epigenetics (which genes are switched on or off).
How these diverse biological signals interact and ultimately contribute to the aging process is still mostly mysterious. But supercentenarians—people over 110 years old—offer clues. This select group doesn’t just live longer, its members are also healthier and often spared from age-related diseases like diabetes, cancer, dementia, and heart problems.
Is the fountain of youth hiding in their biology?
People who live past 100 are rare. A previous study transformed centenarian blood cells into stem cells. Scientists used these to model the aging process at a cellular level and investigate the genetics and other factors underlying centenarian health and lifespan.
Supercentenarians are even rarer. Only one in five million people live past 110 in industrialized nations, making them an especially valuable source of scientific study. When asked if she’d like to contribute, Branyas answered “please study me”—a last wish before she passed away.
A Mixed Bag
Branyas was born in San Francisco but moved to Spain when she was eight. She was very outgoing and maintained a Mediterranean diet full of seafood, olive oil, and vegetables. She walked nearly everywhere and mostly refrained from smoking and heavy drinking.
Her long life wasn’t free of tragedy. She buried her son when he was 52 and watched extended family members pass from common age-related diseases: Alzheimer’s, cancer, kidney failure, and heart disease. Still, Branyas made new friends and maintained a sharp mind as the clock ticked.
The first look into her biology left scientists scratching their heads. Like other elderly people, Branyas had multiple hallmarks of aging. Her telomeres were exceedingly short, suggesting they were less able to protect her DNA as her cells divided. She also had clumps of mutated blood cells linked to vascular diseases and blood cancer. Some of her immune cells—those producing antibodies—showed typical signs of aging. These protective cells often go rogue in the twilight years and attack normal tissue, contributing to chronic inflammation that damages organs.
Yet Branyas wasn’t plagued by any of these age-related killers.
She maintained a cardiovascular and metabolic profile akin to people decades younger. She had little chronic inflammation, and her immune system battled pathogens when needed. At 113, she became the oldest person to survive and recover from Covid-19 in Spain.
These results hint that the markers of aging aren’t necessarily associated with age-related diseases—they could just be signs we’re getting old.
The distinction isn’t academic.
Hallmarks of aging are used in biological “aging clocks” and are being developed into potential early diagnostics for age-related disorders. The decoupling of markers to diseases here “shows that extremely advanced age and poor health are not intrinsically linked,” wrote the team.
Genetic Jackpot
Branyas’s unique genetics offer clues to her resilience.
Mitochondria produce energy in our cells, and they falter as we age. These cellular power plants have their own genes. Branyas’s had several rare genetic variants that kept them humming along. They also mopped up dangerous molecules that increase with age and damage cell structures. Her mitochondria were healthier than women decades younger.
She also had an astonishing library of gene variants that protect against autoimmune diseases, cancer, infections, and metabolic disorders like diabetes. For example, some rare variants involved in lipid metabolism kept her blood vessels clear of fatty buildup.
Her blood work was exceptional for her age. She had low levels of bad cholesterol—this contributes to blockage, heart attacks, and stroke—and high levels of good cholesterol. She also carried protective gene variants linked to the brain.
These “could potentially be contributing to the preservation of cognitive function in extreme old age,” wrote the team.
But genes are only part of the story. Other factors include diet, exercise, environment, upbringing, and mental health. Some of these factors are reflected in your gut microbiome. Researchers have begun mapping bacterial strains to metabolic and brain health.
Branyas had high levels of Bifidobacterium, a type of beneficial bacteria that’s common in yogurt and other fermented dairy products—which she ate three times a day. The bacteria are known for their anti-inflammatory properties and protection of the gut barrier. Levels of Bifidobacterium typically drop with age, and older people who maintain higher levels tend to have healthier immune systems.
Before you go on a yogurt shopping spree, the team stresses no single factor contributed to Branyas’s long life.
Dr. Mary Armanios at Johns Hopkins School of Medicine, who was not involved in the study, agrees. “The genetics of longevity are notoriously confusing,” she told The New York Times. While bad genetics can limit lifespan, “I am not sure good genetics are sufficient to overcome socioeconomic limitations.”
The team is now digging further into Branyas’s biology to see how other hallmarks of aging—such as senescence, or the build-up of toxic “zombie” cells—interact with the other factors.
Source link
#Spanish #Woman #Lived #Heres #Deep #Dive #Genetics #Habits
