Tag Archives: healthy aging

Healthy Vision Month: Reversing Age- and Glaucoma-Induced Vision Loss

July 1, 2021

July marks the beginning of Healthy Vision Month, an awareness initiative led by the National Eye Institute that aims to spotlight the importance of eye health and protection throughout the aging process. As the current scientific understanding of aging expands, so does the knowledge of potential underlying mechanisms that contribute to physical and cognitive degeneration.

One proposed cause of aging is the accumulation of epigenetic noise – or disruptions in gene expression patterns – that lead to decreased tissue function and reduced regenerative abilities. In a recent study, researchers from the Harvard Medical School (HMS) addressed the epigenetics-based theory of aging which postulates that changes in the epigenome cause cellular malfunctions and age-related diseases over time.

Their research continues to explore whether DNA methylation drives cellular change and whether restoring functionality in living organisms is possible. Results report restored vision in mice achieved by restoring aged cells in the retina to their youthful function and a reversal of vision loss in mice with a condition mimicking human glaucoma.

Epigenetic Reprogramming in Mice

The proof-of-concept study represents the first successful attempt at reversing the biological clock in animals via epigenetic reprogramming. To prove this, the team of researchers examined the potential of reversing the age of cells by controlling DNA methylation.

Led by Yuancheng Lu, research fellow at Harvard Medical School, the study’s authors examined whether the regenerative capacity of young animals can be replicated in adult mice by delivering a modified three-gene combination via an adeno-associated virus (AAV) into the retinal ganglion cells of adult mice with optic nerve injury. They targeted cells within the central nervous system as it is the first part of the body affected by aging.

“Having previously found evidence for epigenetic noise as an underlying cause of aging, we wondered whether mammalian cells might retain a faithful copy of epigenetic information from earlier in life that could serve as instructions to reverse aging,” the research team commented.

Restoring Eyesight and Rejuvenating Cells 

Lu and colleagues found that the treatment had multiple beneficial effects on the eye health of mice; it promoted nerve regeneration following optic nerve injury in mice with damaged optic nerves, caused a two-fold increase in the number of surviving retinal ganglion cells after injury, and increased nerve regrowth by five times. These results suggested that the modified gene combination approach was safe and could potentially be used to revolutionize the treatment of ocular degeneration as well as that of other organs affected by aging.

Following their promising findings, Lu and his team partnered with colleagues at Schepens Eye Research Institute of Massachusetts to perform two experiments: one testing whether the three-gene cocktail could restore glaucoma-related vision loss and a second one to test whether this approach could reverse vision loss associated with the regular biological aging process.

The team found that the treatment led to increased nerve cell electrical activity as well as a notable increase in visual acuity, which was measured by the animals’ ability to see moving vertical lines across a screen in a model of glaucoma. “To our knowledge, this is the first example of vision-loss reversal after glaucomatous injury has occurred; previous attempts have focused on neuroprotection delivered at an early stage to prevent further disease progression,” the authors wrote.

Similarly, the treatment had beneficial effects on the vision of elderly mice; it was able to restore vision in older mice with diminishing vision caused by normal aging. Following the treatment, the researchers found reversed patterns of DNA methylation which suggest that DNA methylation is an active agent in the aging process.

“These data indicate that mammalian tissues retain a record of youthful epigenetic information—encoded in part by DNA methylation—that can be accessed to improve tissue function and promote regeneration in vivo,” the authors concluded.

Clinical Implications 

As the first findings that prove the reversal of glaucoma-induced vision loss with no associated negative side effects in the cohort, the latest results will need to be confirmed in further animal work before human trials can be initiated. Nonetheless, the success of the new approach represents a potential breakthrough in regenerative medicine and an array of possible treatment pathways for age-related health conditions.

“Our study demonstrates that it’s possible to safely reverse the age of complex tissues such as the retina and restore its youthful biological function,” said David Sinclair, PhD, co-director of the Paul F. Glenn Center for Biology of Aging Research at HMS, who is senior author of the published paper in Nature. “If affirmed through further studies, these findings could be transformative for the care of age-related vision diseases like glaucoma and to the fields of biology and medical therapeutics for disease at large,” he explained.

Takeaways

If the latest findings can be replicated and validated in future clinical trials, the three-gene combination method could allow for the development of therapies that promote tissue repair across a spectrum of organs and reverse aging and age-related diseases in humans.

Healthy Aging Myths: Physical Deterioration and Impairment are Inevitable

June 18, 2021

As a result of incredible technological and scientific advances, human life expectancy has now doubled. According to data from the World Health Organization, the proportion of the world’s population over the age of 60 is expected to double from 11% to around 22% by the year 2050. With an increasing aging population at hand, it is important for healthcare professionals to combat the many medical myths surrounding the biological aging process which may detrimentally affect patient longevity and well-being.

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Natural Compound Promotes Healthy Aging

July 23, 2020

The seven human sirtuins (SIRT 1-7), or NAD-dependent deacetylases, have been strongly correlated with human longevity due to their connection with metabolic function, aging, and the development of age-related diseases. In recent years, the protein SIRT1 has received the most attention due to its influence on gene regulation, genomic stability, and energy metabolism, garnering interest among the scientific community as a potentially viable pharmacologic therapy for the prevention of several health conditions, including type 2 diabetes, obesity, cancer, as well as cardiovascular and neurodegenerative diseases.

Several compounds have been found to impact the activation of sirtuins, including resveratrol which can be found in red wine, peanuts, pistachios, certain fruits, and cocoa. In small amounts, resveratrol may be able to replicate the health benefits of the steroid hormone estrogen, known for regulating reproduction, protecting against certain age-related diseases such as metabolic syndrome and Alzheimer’s disease.

A new study conducted in the United Kingdom aimed to uncover the mechanisms underlying resveratrol’s health benefits, its association with sirtuin proteins, and its ability to protect against age-related diseases; the latest findings were published in Scientific Reports.

Resveratrol and Healthy Aging

Small amounts of resveratrol – commonly found in red wine, berries, and chocolate – may be able to replicate the beneficial effects of estrogen in preventing metabolic diseases and cognitive decline. Larger amounts, on the other hand, may have the opposite effect, according to the study’s authors.

By activating estrogen receptors, the compound in turn activates sirtuin proteins to exert its physiological effects. Sirtuin proteins play a significant role in the healthy aging process as they control mitochondrial biogenesis, promote DNA repair, and help regulate metabolic function. They are believed to protect the body against several age-related diseases and are thought to have excellent potential drug targets according to the scientific community; however, clinical applications of the proteins remain unclear. Even still, there remains a lack of understanding of how sirtuin signaling translates to increased healthspan in human beings.

Studying Sirtuin-Activating Compounds

Led by Dr. Henry Bayele, molecular biologist at the University College London, researchers conducted an in vitro study of human liver cells which exposed them to a variety of dietary compounds aimed at activating sirtuin proteins. Collectively known as dietary sirtuin-activating compounds (dSTACs),  resveratrol and isoflavones, such as daidzein, are natural activators in comparison with other synthetic compounds developed to spur sirtuin signaling. Researchers found that at low doses, resveratrol increased sirtuin signaling in cells by mimicking estrogen although, at high doses it actively reduced signaling.

“Numerous studies in animals have suggested that these proteins could prolong healthy lifespan by preventing or slowing disease onset,” Dr. Bayele told Medical News Today. “But developing effective drugs or dietary interventions has been frustrated by a lack of a common understanding of how exactly they work in the body’s cells.”

The study’s findings support the notion that small amounts of red wine can promote healthy aging as can other dietary components; Dr. Bayele reported that the compound present in licorice, isoliquiritigenin, is even more effective at activating sirtuins. His research supports the claim that dSTACs can be viewed as “plant estrogens”, benefiting human health by performing functions that estrogen would typically be responsible for.

Implications for Anti-Aging

Emerging evidence supportive of resveratrol’s benefits could lead to the development of alternatives to hormone replacement therapy – which can increase the risk of cardiometabolic disease – for menopause patients. However, further clinical studies are required to confirm whether individuals using dSTACs as estrogen substitutes to promote healthy aging display positive results.

“Regular low doses of resveratrol, such as through moderate consumption of red wine as part of a healthy diet, may be able to provide the benefits of estrogen,” Dr. Bayele explained. “This would apply to both men and women of all ages, but postmenopausal women may feel these benefits the most because they have lower estrogen reserves than men of a similar age.”

Dr. Bayele and his colleagues caution that the effects of dSTACs on cells in vitro found in their study may not reflect their effects in human subjects. For instance, the body may digest resveratrol compounds in the gut or metabolize them in the intestinal microbiota. If they do survive digestion intact, the absorption of the compounds into the bloodstream may be poor or the liver may break them down during digestion. Hence why additional study is needed to develop novel strategies for effectively delivering resveratrol for maximum benefit.