(Image caption: Images of cells in the brain’s hippocampus show that the growth factor
TGF-beta1 (stained red) is barely present in young tissue but ubiquitous in old tissue, where it suppresses stem cell regeneration and contributes to aging)
Whether you’re brainy, brawny or both, you may someday benefit from a drug found to rejuvenate aging brain and muscle tissue.
Researchers at UC Berkeley have discovered that a small-molecule drug
simultaneously perks up old stem cells in the brains and muscles of
mice, a finding that could lead to drug interventions for humans that
would make aging tissues throughout the body act young again.
“We established that you can use a single small molecule to rescue
essential function in not only aged brain tissue but aged muscle,” said
co-author David Schaffer, director of the Berkeley Stem Cell Center
and a professor of chemical and biomolecular engineering. “That is good
news, because if every tissue had a different molecular mechanism for
aging, we wouldn’t be able to have a single intervention that rescues
the function of multiple tissues.”
The drug interferes with the activity of a growth factor,
transforming growth factor beta 1 (TGF-beta1), that Schaffer’s UC
Berkeley colleague Irina Conboy showed over the past 10 years depresses
the ability of various types of stem cells to renew tissue.
“Based on our earlier papers, the TGF-beta1 pathway seemed to be one
of the main culprits in multi-tissue aging,” said Conboy, an associate
professor of bioengineering. “That one protein, when upregulated, ages
multiple stem cells in distinct organs, such as the brain, pancreas,
heart and muscle. This is really the first demonstration that we can
find a drug that makes the key TGF-beta1 pathway, which is elevated by
aging, behave younger, thereby rejuvenating multiple organ systems.”
The UC Berkeley team reported its results in the current issue of the journal Oncotarget. Conboy and Schaffer are members of a consortium of faculty who study aging within the California Institute for Quantitative Biosciences (QB3).
Depressed stem cells lead to aging
Aging is ascribed, in part, to the failure of adult stem cells to
generate replacements for damaged cells and thus repair the body’s
tissues. Researchers have shown that this decreased stem cell activity
is largely a result of inhibitory chemicals in the environment around
the stem cell, some of them dumped there by the immune system as a
result of chronic, low-level inflammation that is also a hallmark of
In 2005, Conboy and her colleagues infused old mice with blood from
young mice – a process called parabiosis – reinvigorating stem cells in
the muscle, liver and brain/hippocampus and showing that the chemicals
in young blood can actually rejuvenate the chemical environment of aging
stem cells. Last year, doctors began a small trial to determine whether
blood plasma from young people can help reverse brain damage in elderly
Such therapies are impractical if not dangerous, however, so Conboy,
Schaffer and others are trying to track down the specific chemicals that
can be used safely and sustainably for maintaining the youthful
environment for stem cells in many organs. One key chemical target for
the multi-tissue rejuvenation is TGF-beta1, which tends to increase with
age in all tissues of the body and which Conboy showed depresses stem
cell activity when present at high levels.
Five years ago, Schaffer, who studies neural stem cells in the brain,
teamed up with Conboy to look at TGF-beta1 activity in the hippocampus,
an area of the brain important in memory and learning. Among the
hallmarks of aging are a decline in learning, cognition and memory. In
the new study, they showed that in old mice, the hippocampus has
increased levels of TGF-beta1 similar to the levels in the bloodstream
and other old tissue.
Using a viral vector that Schaffer developed for gene therapy, the
team inserted genetic blockers into the brains of old mice to knock down
TGF-beta1 activity, and found that hippocampal stem cells began to act
more youthful, generating new nerve cells.
Drug makes old tissue cleverer
The team then injected into the blood a chemical known to block the
TGF-beta1 receptor and thus reduce the effect of TGF-beta1. This small
molecule, an Alk5 kinase inhibitor already undergoing trials as an
anticancer agent, successfully renewed stem cell function in both brain
and muscle tissue of the same old animal, potentially making it stronger
and more clever, Conboy said.
“The key TGF-beta1 regulatory pathway became reset to its young
signaling levels, which also reduced tissue inflammation, hence
promoting a more favorable environment for stem cell signaling,” she
said. “You can simultaneously improve tissue repair and maintenance
repair in completely different organs, muscle and brain.”
The researchers noted that this is only a first step toward a
therapy, since other biochemical cues also regulate adult stem cell
activity. Schaffer and Conboy’s research groups are now collaborating on
a multi-pronged approach in which modulation of two key biochemical
regulators might lead to safe restoration of stem cell responses in
multiple aged and pathological tissues.
“The challenge ahead is to carefully retune the various signaling
pathways in the stem cell environment, using a small number of
chemicals, so that we end up recalibrating the environment to be
youth-like,” Conboy said. “Dosage is going to be the key to rejuvenating
the stem cell environment.”
💬I had the day off but didn’t really do much, which is okay with me
💬 watadad took the day off too but did different stuff
💬 I must admit I am emotional because 19 turns 20 on Monday.
💬 Skipping the gym today and that is also okay with me.
💬 I also would really like a drink and a cigarette in case you were wondering
“I’m 37 and I was told recently I was too old to play the lover of a man who was 55. It was astonishing to me.It made me feel bad, and then it made feel angry, and then it made me laugh.” - Maggie Gyllenhaal
Hollywood finds itself under increasing scrutiny in 2015 for failing to represent women fairly on screen and behind the cameras. Read article
If you haven’t yet seen the viral video showing a couple in their 20s get transformed by makeup artists to look age 50, 70 and 90, take five minutes to watch it (below). The video will make you think about sterotypes of aging and also about what it means to grow old with a partner.
Brain health is the second most important component in maintaining a
healthy lifestyle according to a 2014 AARP study. As people age they can
experience a range of cognitive issues from decreased critical thinking
to dementia and Alzheimer’s disease. In the March issue of Food
Technology published by the Institute of Food Technologists (IFT),
contributing editor Linda Milo Ohr writes about eight nutrients that may
help keep your brain in good shape.
1. Cocoa Flavanols:
Cocoa flavanols have been linked to improved circulation and heart
health, and preliminary research shows a possible connection to memory
improvement as well. A study showed cocoa flavanols may improve the
function of a specific part of the brain called the dentate gyrus, which
is associated with age-related memory (Brickman, 2014).
2. Omega-3 Fatty Acids:
Omega-3 fatty acids have long been shown to contribute to good heart
health are now playing a role in cognitive health as well. A study on
mice found that omega-3 polyunsaturated fatty acid supplementation
appeared to result in better object recognition memory, spatial and
localizatory memory (memories that can be consciously recalled such as
facts and knowledge), and adverse response retention (Cutuli, 2014).
Foods rich in omega-3s include salmon, flaxseed oil, and chia seeds.
3. Phosphatidylserine and Phosphatidic Acid:
Two pilot studies showed that a combination of phosphatidylserine and
phosphatidic acid can help benefit memory, mood, and cognitive function
in the elderly (Lonza, 2014).
4. Walnuts: A diet
supplemented with walnuts may have a beneficial effect in reducing the
risk, delaying the onset, or slowing the progression of Alzheimer’s
disease in mice (Muthaiyah, 2014).
Citicoline is a natural substance found in the body’s cells and helps in
the development of brain tissue, which helps regulate memory and
cognitive function, enhances communication between neurons, and protects
neural structures from free radical damage. Clinical trials have shown
citicoline supplements may help maintain normal cognitive function with
aging and protect the brain from free radical damage. (Kyowa Hakko
6. Choline: Choline, which is associated with liver
health and women’s health, also helps with the communication systems for
cells within the brain and the rest of the body. Choline may also
support the brain during aging and help prevent changes in brain
chemistry that result in cognitive decline and failure. A major source
of choline in the diet are eggs.
7. Magnesium: Magnesium
supplements are often recommended for those who experienced serious
concussions. Magnesium-rich foods include avocado, soy beans, bananas
and dark chocolate.
8. Blueberries: Blueberries are known
to have antioxidant and anti-inflammatory activity because they boast a
high concentration of anthocyanins, a flavonoid that enhances the
health-promoting quality of foods. Moderate blueberry consumption could
offer neurocognitive benefits such as increased neural signaling in the
In recent years, public health concerns about post-traumatic stress disorder (PTSD) have risen significantly, driven in part by affected military veterans returning from conflicts in the Middle East and elsewhere. PTSD is associated with number of psychological maladies, among them chronic depression, anger, insomnia, eating disorders and substance abuse.
Writing in the May 7 online issue of American Journal of Geriatric Psychiatry, researchers at University of California, San Diego School of Medicine and Veterans Affairs San Diego Healthcare System suggest that people with PTSD may also be at risk for accelerated aging or premature senescence.
“This is the first study of its type to link PTSD, a psychological disorder with no established genetic basis, which is caused by external, traumatic stress, with long-term, systemic effects on a basic biological process such as aging,” said Dilip V. Jeste, MD, Distinguished Professor of Psychiatry and Neurosciences and director of the Center on Healthy Aging and Senior Care at UC San Diego, who is the senior author of this study.
Researchers had previously noted a potential association between psychiatric conditions, such as schizophrenia and bipolar disorder, and acceleration of the aging process. Jeste and colleagues determined to see if PTSD might show a similar association by conducting a comprehensive review of published empirical studies relevant to early aging in PTSD, covering multiple databases going back to 2000.
There is no standardized definition of what constitutes premature or accelerated senescence. For guidance, the researchers looked at early aging phenomena associated with non-psychiatric conditions, such as Hutchinson-Gilford progeria syndrome, HIV infection and Down’s syndrome. The majority of evidence fell into three categories: biological indicators or biomarkers, such as leukocyte telomere length (LTL), earlier occurrence or higher prevalence of medical conditions associated with advanced age and premature mortality.
In their literature review, the UC San Diego team identified 64 relevant studies; 22 were suitable for calculating overall effect sizes for biomarkers, 10 for mortality.
All six studies looking specifically at LTL found reduced telomere length in persons with PTSD. Leukocytes are white blood cells. Telomeres are stretches of protective, repetitive nucleotide sequences at the ends of chromosomes. These sequences shorten with every cell replication and are considered a strong measure of the aging process in cells.
The scientists also found consistent evidence of increased pro-inflammatory markers, such as C-reactive protein and tumor necrosis factor alpha, associated with PTSD.
A majority of reviewed studies found increased medical comorbidity of PTSD with several targeted conditions associated with normal aging, including cardiovascular disease, type 2 diabetes, gastrointestinal ulcer disease and dementia.
Seven of 10 studies indicated a mild-to-moderate association of PTSD with earlier mortality, consistent with an early onset or acceleration of aging in PTSD.
“These findings do not speak to whether accelerated aging is specific to PTSD, but they do argue the need to re-conceptualize PTSD as something more than a mental illness,” said first author James B. Lohr, MD, professor of psychiatry. “Early senescence, increased medical morbidity and premature mortality in PTSD have implications in health care beyond simply treating PTSD symptoms. Our findings warrant a deeper look at this phenomenon and a more integrated medical-psychiatric approach to their care.”
Barton Palmer, PhD, professor of psychiatry and a coauthor of the study, cautioned that “prospective longitudinal studies are needed to directly demonstrate accelerated aging in PTSD and to establish underlying mechanisms.”
Pictured: Human chromosomes shown in blue, with telomeres appearing as yellow pinpoints. Image courtesy of the National Institutes of Health.
New work by the Douglas Mental Health University Institute (CIUSSS de
l’Ouest-de-l’île-de-MontréalI) computational neuroscientist Mallar
Chakravarty, PhD, and in collaboration with researchers at the Centre
for Addiction and Mental Health (CAMH) challenges in a thrilling way the
long-held belief that a larger hippocampus is directly linked to
improved memory function.
The size of the hippocampus, an important structure in the brain’s
memory circuit, is typically measured as one method to determine the
integrity of the memory circuit. However, the shape of this structure
is often neglected. Using a novel algorithmic technique to map the
hippocampus, Dr. Chakravarty, Assistant Professor, Department of
Psychiatry at McGill University, is shedding new light on its shape. The
algorithm developed by the team identifies individuals with differently
shaped hippocampi. In fact, the study has found that while stereotypic
shapes exist for this structure, individuals with a broad-shaped
hippocampus tend to perform better on various tests that assess memory.
In the study, these shape differences were better predictors of memory
function than the bulk volume of the hippocampus.
“This exciting new finding may help us improve our understanding of
how to preserve the memory circuit and its function. This work shows the
value of multidisciplinary research, as it required the close
collaboration of engineers, computer scientists and psychiatrists to
complete this work,” says Dr. Chakravarty, senior author on the study.
Chakravarty’s student Julie Winterburn notably worked on this project,
and was co-first author with Dr. Aristotle Voineskos of CAMH’s Campbell
Family Mental Health Research Institute in Toronto.
Why it matters
Improving our understanding of the geometry of different structures
may have significant implications in understanding neuropsychiatric
disorders, such as Alzheimer’s disease, where memory function is
significantly compromised. Given the aging demographics of Quebec and
Canada, uncovering clues on how to improve memory function, one of the
main impairments reported (even in healthy aging), will be critical to
relieving the overwhelming burden our health care system currently
faces. The results of this recent research are published in Human Brain
Mapping, a peer-reviewed scientific journal.
Scientists have discovered that the deteorioration of the tightly-packed bundles of DNA that are responsible for our normal cell functioning is actually reversible, and figuring out how this process works could enable new treatments for age-related diseases like Alzheimer’s.
Researchers from the Salk Institute in the US and the Chinese Academy of Science made the discovery while studying the underlying causes of Werner syndrome - a genetic disorder that causes affected individuals to age more rapidly than normal.
People with this condition suffer age-related diseases early in life, such as cataracts, type-2 diabetes, osteoporosis, and cancer, and often die prematurely in their 40s or 50s.
The team found that the genetic mutations responsible for this syndrome caused densely packed DNA - known as heterochromatin - to become destabilised, which serves to disrupt normal cellular functions and caused the cells to age prematurely.
I have been alive for
Yet sometimes it feels as if I was born yesterday,
Like it was only a couple of hours ago that I opened my eyes
For the very first time.
Like I had my whole life ahead of me to be whoever
I wanted to be.
Yet sometimes I feel like I am a hundred years old,
Like time has passed so slowly that I
Feel as though I’ve lived many lives.
Like I’ve made so many experiences, mistakes, and memories,
That it’s impossible for me to be so young.
Sometimes I feel like I’m never aging,
Even though every second that passes by,
I get older.
I have been alive for,
10, 326,046 minutes.
Yet time is just a number made up by humanity.
Sometimes I’ve been alive for 36,524 days.
Sometimes for only one.
Sometimes I’ve experienced 876,581 hours.
Sometimes only 24.
I have been alive for,
10, 326,050 minutes.
And every second I grow older,
And every second I stay the same.