When Jeanne Calment passed away at 122, she left scientists bewildered by the extraordinary length of her life. Despite being physically energetic throughout much of her life, she also had a habit of smoking daily and enjoyed drinking wine – lifestyle choices that are commonly associated with reducing one’s healthy lifespan.
Teasing aside, it’s challenging to do so effectively. As individuals age, adopting a balanced food regimen, regular training, and healthy habits can significantly alter their wellbeing’s trajectory. Genetics also plays a crucial role, particularly during one’s twilight years. Since human lifespans are relatively long compared to other species, designing experiments to test these ideas proves challenging. Conducting long-term studies on large populations to track individual aging is impractically expensive, with results potentially taking numerous years to materialize. Most studies have shifted their focus towards understanding aging in animals with relatively short lifespans, such as flies, rodents, and dogs.
What if scientists could cultivate human cells that have been optimized for longevity, allowing them to model the effects of aging on a cellular level and potentially unlock new insights into extending human lifespan?
A groundbreaking new study, published recently, precisely achieved this outcome. By leveraging a unique dataset from centenarians—the world’s oldest individuals—scientists rewrote the code for mature blood cells, successfully converting them into induced pluripotent stem cells (iPSCs).
Stem cells carry the genetic instructions from their parent cells, serving as a biological template for their development and function. The crew established a biobank of cells that could facilitate research into longevity-related genes.
“Fashioned by human aging, longevity, and resilience against disease, the scarcity of practical testing grounds for novel interventions is a major challenge.”
Researchers have publicly disseminated their findings on the so-called “super-aging” stem cells, furthering knowledge of the genetic and molecular mechanisms underlying a healthier, more extended lifespan by sharing them with the scientific community.
Without naming Chiara Herzog or specifying her affiliation with Kings College London, the revised text would be:
A long-time researcher has described this financial institution as “thrilling”, despite not being involved in the study.
Treasured Useful resource
Centenarians are uncommon. According to a Pew Research Center analysis, based on data from the US Census Bureau, Hispanic individuals comprise approximately 18% of the country’s population. Approximately 722,000 people worldwide have reached the remarkable milestone of celebrating their 100th birthday, a mere fraction of the planet’s current population.
Centenarians don’t simply dwell longer. Individuals who are physically fit and active tend to be healthier, even into old age, and are less prone to experiencing age-related health issues such as dementia, Type 2 diabetes, certain types of cancer, and strokes? Many individuals avoid addressing these detrimental health concerns until the very end.
What makes them particular? In recent years, numerous studies have delved into the realm of genetics, exploring which genes are actively involved in healthy aging processes – or conversely, how they contribute to declining health and well-being as we grow older. Researchers have created tests that utilize a multitude of biomarkers to determine an individual’s organic age – the extent to which their bodily systems are functioning optimally. Despite their advanced years, centenarians consistently defy conventional expectations, exhibiting a unique genetic profile and remarkable physiological characteristics that belie their extraordinary age.
Founded in 1995, the New England Centenarian Study sought to tap into the vast educational opportunities presented by advancing age. The research, led by Tom Perls and Stacy Andersen at Boston College, has successfully recruited centenarians through various methods, including voter registries, news articles, and targeted mailings to senior care facilities.
As a consequence of the potential genetic underpinning of longevity, children whose parents had lived into old age were also recruited for participation, with their spouses acting as controls. Members reported on their socioeconomic status and medical histories. Researchers investigated individuals’ cognitive functioning during video conferencing sessions and concurrently evaluated their mental health to identify any potential concerns. Blood samples were obtained from a select few members. Despite advancing age, a significant number of centenarians surprisingly retain mental acuity, enabling them to manage their daily needs with remarkable independence.
Tremendous-Ager Stem Cells
The team initially scrutinized the ageing clocks that had accumulated considerable wear and tear. These measurements reveal that methylation effectively silences gene expression without modifying the underlying DNA sequence. Centenarians’ average age disparity from their chronological age was approximately 6.5 years.
What remarkable benefits did their offspring exhibit due to the anti-aging treatment? Results showed varying levels of organically aged samples, with some exhibiting increased aging and others experiencing a decline. The discovery could be attributed to the diversity of individuals inheriting a genetic “fingerprint” linked to longevity, noted the research team.
Researchers subsequently rewrote the genetic blueprints of blood cells derived from 45 centenarians to generate induced pluripotent stem cells (iPSCs). Individuals chosen for the study exhibited a remarkable spectrum of overall wellness and performance outcomes. Given their advanced age, they had initially assumed that reversing the clock wouldn’t be effective for rejuvenating past blood cells.
Fortunately, they had been unsuitable. The numerous proteins verified that the induced pluripotent stem cells (iPSCs) were indeed healthy and capable of generating diverse cell types. Despite this, the vast majority of cells in these individuals demonstrated remarkable preservation of their genomic integrity; however, a fascinating finding emerged from analyzing cells from three male centenarians: a subtle deficiency in Y-chromosome material was discovered.
Research has previously identified a comparable deletion pattern in blood cells from male individuals older than 70 years. It may serve as an indicator of aging and potentially poses a risk factor for age-related conditions similar to cancer and cardiovascular disease. Women generally live longer than men. The study’s discoveries unlock fresh avenues for in-depth examination of the mechanisms driving Y-chromosome loss.
Unraveling Growing older
Researchers have discovered that reprogramming blood cells into stem cells effectively eliminates signs of aging, most notably those linked to the cells’ epigenetic profile. Epigenetic mechanisms regulate gene expression, determining whether specific genes are activated or silenced, and this process undergoes natural changes as individuals age. Despite superficial differences, the fundamental genetic code remains unchanged.
If the keys to longevity lie, at least in part, encoded within our genetic makeup, these extraordinary stem cells could provide valuable insights for researchers, allowing them to uncover the mechanisms by which genes protect or damage our biological clocks, thus sparking innovative ideas that may ultimately help slow down the aging process.
By manipulating a solitary occasion, researchers successfully coaxed the stem cells to transform into cortical neurons. The cerebral cortex, comprising these neurons, forms the outermost layer of the brain responsible for processing sensory information and facilitating higher-level thinking. They are also the first to degenerate in dementia or Alzheimer’s disease. Individuals who have lived to 100 years or older, known as centenarians, have been found to more effectively combat and recover from injuries, which may be attributed to their ability to rapidly limit the spread of toxic proteins that typically accumulate with age?
Scientists are also leveraging these cells to assess their capacity for resistance. One notable experiment has successfully generated cultures that produce wholesome neurons, immune cells, and astrocytes. Researchers have successfully generated supporting cells that play a crucial role in maintaining the brain’s overall health, by employing centenarian stem cells. While astrocytes have increasingly been linked to Alzheimer’s disease, determining their role in humans has proven challenging due to difficulties in studying these cells in individuals. These stem cells, derived from centenarians, offer a promising approach forward.
Each line of centenarian stem cells is directly tied to the corresponding donor’s demographic information, as well as their cognitive and physical condition. This additional data may provide valuable insights to researchers when choosing an optimal centenarian cell line for their studies on diverse aspects of aging. By reprogramming cells into various tissue types that naturally degenerate with age – muscle groups, cardiovascular cells, or immune cells – researchers can now gain insight into how aging affects distinct organs and the rate at which they deteriorate.
“The study’s outcome yields a singularly valuable asset for investigating human longevity and resilience, poised to fuel the development and verification of innovative treatments for age-related diseases,”
