Reversing Age-Related Impairment and Immunity

While the average life-expectancy for humans continues to increase, a longer life span has been tied to an uptick in age-related disease and impairment across the globe. As a result of a declining immune system, the growing elderly population is more prone to infectious diseases – including influenza and COVID-19. Additionally, this group is commonly affected by age-related frailty, which has a significant negative impact on quality of life. The high level of care and involvement required to maintain the health of these patients has the potential to bear a growing burden on the healthcare system which is part of the reason underlying research efforts in the field of human longevity.

The current body of knowledge suggests the role of chronic low-grade inflammation in the biological aging process and development of age-related diseases; scientific evidence implicates that the presence of inflammation in the body accelerates aging. Hoping to uncover more information about additional factors that may contribute to an accelerated process and potential methods of reversing them, a team of researchers from the Department for BioMedical Research at the University of Bern conducted a study with findings published in Nature Metabolism.

Age-Related Frailty and Immunity

Under Bernese guidance, Dr. Mario Noti and Dr. Alexander Eggel aimed to identify new approaches to improving health-span in an ever-increasing aging population by focusing on adipose tissue eosinophils (ATEs) present in humans and mice. These immune cells found in visceral adipose tissue, otherwise known as belly fat, play an essential role in regulating inflammation and could be used to reverse aging processes; these cells are important in the control of obesity-related inflammation and metabolic disease as they are responsible for maintaining local immune homeostasis. Increasing age is tied to a decrease in eosinophils in adipose tissue and an increase in pro-inflammatory macrophages – turning belly fat into a source of pro-inflammatory activity.

Role of Eosinophils in Chronic Inflammation

The study’s authors demonstrated that visceral adipose tissue contributed to the development of chronic low-grade inflammation. They found that ATEs undergo major age-related changes in distribution and function associated with impaired adipose tissue homeostasis and systemic low-grade inflammation in human subjects as well as mice. However, exposure to a young systemic environment  was able to partially restore ATE distribution in aged subjects by reducing adipose tissue inflammation.

“In different experimental approaches, we were able to show that transfers of eosinophils from young mice into aged recipients resolved not only local but also systemic low-grade inflammation,” the researchers told ScienceDaily. ”In these experiments, we observed that transferred eosinophils were selectively homing into adipose tissue.”

Using an adoptive transfer or eosinophils from young mice to aged subjects, researchers were able to restore ATE distribution and sufficiently mitigate age-related local and systemic low-grade inflammation. As a result of the transfer, youthful systemic environments were restored and systemic rejuvenation took place in aged mice. Changes were both physical – assessed by endurance and grip strength tests – and immune-related – manifested in improved vaccination responses.

Dr. Noti and Dr. Eggel’s findings support the critical function of adipose tissue as a source contributing to accelerated aging and uncover the new role of eosinophils in sustaining adipose tissue homeostasis and thus, promoting healthy aging.

Because the age-related changes in adipose immune cell distribution were confirmed in human subjects, the latest study may have significant positive implications for the anti-aging medicine field when translated into clinical practice. Age-related frailty and immune decline may be halted and potentially even reversed as a result of this novel cell-based therapeutic approach.

“Our results indicate that the biological processes of aging and the associated functional impairments are more plastic than previously assumed,” Dr. Noti stated. “A future direction of our research will be to now leverage the gained knowledge for the establishment of targeted therapeutic approaches to promote and sustain healthy aging in humans,” his research partner Dr. Eggel concluded.

 

Natural Compound Promotes Healthy Aging

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.

Return to Non-Emergent Care: Common Reopening Challenges Facing Your Practice

As practices begin to reopen to serve the needs of patients and begin delivering non-emergent care, many physicians may be wondering what the appropriate protocols in the pandemic environment are and how best to support their patients at this time. In addition, the new clinical setting presents its own set of challenges that require a strategic and unified approach. Physicians must now balance the need for in-person visits – which are crucial for critical medical care and revenue generation – with the risk of COVID-19 spread. Telemedicine has proven an adequate solution to patient management, however, it may not be a sufficient method of delivering care for all patients and some demand in-office appointments despite the ongoing virus spread.

Dr. Sachin Dave, an internist of the Indiana Internal Medicine Consultants stresses the importance of educating patients and communicating the risks to them. “My older patients actually insist on coming to see me in person,” he told Medscape in an interview, “I have to tell them it’s not safe.” Minimizing risk is paramount in the process of reopening medical practices across the United States and the globe; physicians must weigh the risks of increasing patient volume with patient and staff safety.

To assist healthcare practitioners in safely transitioning back to in-person care, Medscape has outlined some common challenges they may face in the reopening process, and how best to mitigate them.

1.     Unclear or Nonexistent Policies and Protocols

While physicians and other staff members may be aware of the COVID-19 prevention rules implemented to help mitigate virus transmission, patients need to be made aware of them preferably in a readily available document; it is important to develop formal protocols for all to follow to minimize confusion and ensure safety.

This includes enforcing mandatory mask wear for both staff and patients, setting up facilities in accordance with social distancing guidelines, having alternate waiting areas or asking patients to wait in their cars if the space gets too crowded, and other protective strategies.

Ensure all patients understand and agree to adhere to your new policies before they come in; in addition, they should be triaged over the phone per CDC guidelines before attending an in-office visit. Without a formal framework, refusing care or assessment of patients who do not comply with guidelines may lead to patient abandonment claims, making clear policies paramount at this time.

2. Too Many Patients, Too Soon

According to data from the Medical Group Management Association (MGMA), practices report an average 55% decrease in revenue and 60% decrease in patient volume since the COVID-19 crisis began. As a result, experts believe practices may be tempted to ramp up capacity immediately to restore prior patient volume. However, this period requires slow and carefully implemented safety protocols.

Physicians and their patients are encouraged to take advantage of telehealth services while they remain reimbursable at parity. The elevated demand for online care is forecasted to continue growing as more patients become comfortable with the technology and services become more advanced. While some doctors want to see an overload of patients immediately upon reopening, there has to be a limit on the number of patients coming into an office as welcoming too many patients too fast can have dire consequences.

3. Lack of Communication

Another potential pitfall is under-communication; patients may not be aware that your practice has reopened or plans to do so. It is important to consistently update your practice’s website, send out letters or newsletters to patients, maintain phone and email contact, post signs explaining reopening protocols, and keep everyone in the loop. The CDC has provided phone advice line tools that practices can adapt to their needs to keep patients informed.

Instead of under-communicating, physicians are encouraged to over-communicate to their patients as well as their staff, making sure they are made aware of the extra precautions being taken to prioritize their health and safety. Practice staff should also be aware of policy changes to minimize confusion.

Experts believe that practices can emerge stronger from the pandemic if they promote strong patient education and build up goodwill at this time. Leverage the patient portal, using it as a trusted resource to inform patients about COVID-19 and preventative measures being taken at your practice.

4. Inadequate Staff Training

Some staff members may be apprehensive about returning to work as a result of virus-related fears. Clear guidance is needed to ensure safety, manage expectations, and offer flexibility with scheduling to address potential challenges before they occur.

Properly training staff members is essential to their safety and that of your patients; specific guidelines for staff – such as designating eating areas, staggering appointments – should be clearly articulated and readily available. Many staff members may not be used to donning and removing personal protective equipment or wearing masks when working with patients. Training staff members will help reassure patients that safety protocols are being adhered to.

5. Neglecting Documentation

With the changing standard of care, a consistent workflow is paramount. This includes proper documentation, communication with staff and patients, and the use of established systems aimed at mitigating COVID-19 risk. Experts recommend keeping an administrative file used to track new protocols, policies, and any incidents or breaches for future use.

6. Forgetting About Personal Mental and Physical Health

Physicians should be cognizant of the high potential of burnout and mental health state  of their staff, their colleagues, and themselves. Mental exhaustion as a result of the persisting COVID-19 crisis and ongoing societal tensions is affecting all members of the population and has the potential to carry over to medical practices. To protect their mental and physical health as well as that of their staff members, physicians are encouraged to prioritize maintaining a positive culture at their practice – one in which everyone feels safe, taken care of and helps each other.

Practices and healthcare professionals located in areas which have deemed non-emergent care facilities eligible to reopen safely should take into consideration the aforementioned challenges and common pitfalls that may impede a smooth return to routine care. For those in search of comprehensive reopening recommendations and guidelines, The Doctors Company has developed an extensive checklist outlining the necessary steps for transitioning to in-person care – accessible here.