Tag Archives: Reduced risk of disease

Future of Anti-aging Medication: Senotherapy

Individual controls aging, ,

Introduction

Because all of our life phases (birth to adulthood) are driven by genetic programs, one naturally assumes genetic programs dictate age changes.  Sadly, they do not (see Insight 1).  In fact our genes contribute at most, 25% to aging.  Thus, 75% of aging is due to one’s lifestyle choices.

Unfortunately, study results show that only a small percentage of elderly actually practice validated and effective activities to minimize aging.  Therefore, for the majority of elderly, this blog brings deliverance in the knowledge of the rapidly developing pharmacological field of senotherapy, with the purpose to reduce disease risk by retarding aging.  It is hoped that senotherapy becomes a supplement to anti-aging lifestyle choices practiced by the individual.

This blog will discuss senotherapy and its merits.  However, since safe and effective senotherapy is not available today but clearly in expected in the near future, it is worthwhile to review known beneficial and anti-aging lifestyle choices.

Proven Activities to Retard Aging

Until senotherapy is common practice, there are many effective ways to retard aging and hence, reduce the risk for disease.  Some of these activities are: 

Pro-Active

1.  COMMITMENT TO A COMPLETE EXERCISE PROGRAM that includes aerobics and stretch (Insight 4: Anti-aging benefits of aerobic and stretch exercises), resistance exercises (Insight 2), balance exercises (Insight 5) .  Numerous benefits include enhanced blood flow to all tissues, stable heart function, stronger muscles, greater flexibility and balance. These all translate into greater independence, reduced risk of falls and decreased disease risk. Other benefits include improved insulin sensitivity especially benefiting from a program of resistance exercise (Insight 18 Vicious Cycle – Aging and Declining Blood Sugar Control).

2.  ADHERENCE TO THE MEDITERRANEAN DIET, a plant-based diet  reduces risks for many diseases including type 2 diabetes, cardiovascular disease, cancers, Alzheimer’s and Parkinson’s diseases (Insight 10). 

3,  PRACTICE OF POSITIVE NEUROPLASTICITY that consist of a) continual engagement in career activities by not retiring, part time retirement, volunteer work or a new career, b) learning new skills e.g. foreign language or musical instrument, c) maintaining social contacts and d) physical exercise program (Insight 6 ).  These activities promote optimal brain function.

4.  AWARENESS OF SPECIFIC MAINTENANCE/PRESERVATION ACTIVITIES OF SENSORY ORGANS can preserve normal sight, hearing, smell and tactile/proprioceptive senses.  This awareness includes use of reading glasses to correct age-related loss of near vision; avoidance of exposure to chronic loud noises e.g. rock concerts, yard tools, to prevent hearing loss (Insight 16 How to Prevent Hearing Loss ), avoidance of exposure to harsh chemicals e.g. Clorox to prevent decline in smell and routine balance exercises to prime sensory neurons (proprioceptors) in joints, ligaments, muscles (Insight 5 – Optimizing Balance).  Accidents, falls, fuzzy thinking results from diminished sensory function.  Physiologically normal sensory function is essential for independent living.    

Avoidance

1.  CHOOSE ACTIVITIES THAT AVOID THE FOLLOWING:   UVA radiation is a known cause of aging skin and skin cancer.  The risk of both are lessened dramatically with routine use of sunscreens, termed broad spectrum.  Compounds classified as broad spectrum sunscreens specifically block UVA  rays from penetrating deep into the skin (Insight 12 -Ways to forestall aging of the skin). 

2. Avoidance of tobacco smoking is absolutely necessary to prevent accelerated aging and enhanced risk of disease including cardiovascular and cancer diseases.  Each inhalation brings in over 1000 toxins that damage precious molecules e.g. DNA, proteins, and lipids.  There are several ways to quit smoking.  Success can result from use of nicotine replacement therapies such as transdermal nicotine patch, nicotine gum, nicotine lozenge and/or pharmaceuticals such as the anti-depressant, bupropion (Zyban) or partial nicotine agonist, varenicline (Chantix) plus physician support with advice and behavioral therapy.

Anti-aging Medication: Senotherapy

Senotherapy is the pharmacological approach to eliminate or modify aged or senescent cells.  This approach will undoubtedly serve those who choose to ignore the clinically proven activities discussed above to retard aging and reduce the risk for disease.  The validated activities delineated above are critically important because they reduce the stress-related factors that cause a cell to age.

Background on Senotherapy

It has been known for some time now that as one ages, the cells in each tissue begin to change.  They increase in size, cease normal function and become bad actors, producing a myriad number of unwanted substances e.g. pro-inflammatory and other destructive agents that harm near-by healthy cells.  Sadly, senescent cells skirt around the biological mechanisms to identify and eliminate them.  Hence, their presence clearly promotes aging of tissues and sets the stage for the first steps to disease.

In consideration of the serious consequences of persistent senescent cells, research interest in senotherapy has blossomed significantly.  Approximately 12 compounds have been evaluated in aged mice or mouse models of disease.  The results of these studies have in many cases been dramatic with reduction in the number of senescent cells and their debilitating functions.  For example, reports show benefits on improved function in kidneys, skeletal muscles, liver and lungs.  Also reported were reduced inflammation in the brain, and increased skeletal muscle regeneration.  

Pilot Studies in Man

Several small pilot studies in man have used senotherapy in conditions of pulmonary fibrosis, macular degeneration, and cardiovascular disease.  Although the results are promising, caution is needed since these studies were of short duration (days/weeks), included few participants (7-13) and used a single dose.  Future studies will surely address these issues and others such as long term adverse effects.

Summary of discussion on anti-aging strategies. What the individual can do and what might be in the future as an aid.
Anti-aging Strategies

Conclusions

In this rush to pharmacologically retard aging, we should not ignore the wealth of data from clinical trials that already exists to minimize cellular aging as continually discussed in prior blogs.  Senotherapy seeks to develop selective drugs to eliminate or minimize the effects of aged cells.  Scientific interest is high because aging is the main risk factor for disease, so to eliminate age changes will significantly decrease disease incidence. 

Select reference (Pubmed)

Bilder, G. Human Biological Aging: from macromolecules to organ-systems.  John Wiley & Sons Publishers, Hoboken, New Jersey, 2016.

Iftikhar U et al., How to Effectively Help Patients Stop Smoking: A Primer for Cardiologists. Canadian Journal of Cardiology 38: 1442-1445, 2022.

Justice JN et al., Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine 40:554-563, 2019.

L’Hote V. et al., From the divergence of senescent cell fates to mechanisms and selectivity of senolytic . Open Biol. 12: 220171, 2022.

Raffaele M., Vinciguera M. The costs and benefits of senotherapeutics for human health.  Lancet Healthy Longev 3: e67–77, 2022.

West, R.  Tobacco smoking: Health impact, prevalence, correlates and nterventions. Psychology & Health,  32:  1018-1036, 2017.

Insight 10-Best Longevity diet = Mediterranean Diet

Diet, Individual controls aging,

Best diet for longevity

I previously discussed in Insight 8 that severe caloric restriction retards the onset of many diseases and increases longevity in animal models of aging (including the monkey).  I subsequently presented the status of the future caloric-mimetic drugs. These drugs are predicted to offer the same benefits (health and longevity) of caloric restriction minus the pain of caloric restriction (Insight 9).  However, in the interim until the advent of efficacious caloric-mimetic drugs, the question remains as to what is the best diet for longevity building.  The best answer to date is the Mediterranean diet.  It is the diet with the most convincing scientific support.  Most importantly, adherence to this diet is associated with a decrease in the incidence of cardiovascular disease, the major cause of death in our society.  As a result, disease reduction indirectly increases lifespan.  

Components of the Mediterranean Diet

The Mediterranean diet entails consumption of whole grains, legumes, fruits, vegetables, nuts, fish and olive oil, wine in moderation, and a low-moderate intake of meat, dairy products, processed foods and sweets (Vitale et al., 2018).  This ~2000 calorie/day diet derives more calories from plant based foods than from meat based foods and fat consumption is largely from mono- and polyunsaturated fats.  More details are presented in the adjacent table.  This table is the result of an extensive systemic review (59 studies) of the health effects of the Mediterranean diet (D’Alessandro et al., 2019).  The authors were able to assess the effect of each food group on disease prevention. From that, they developed the frequency and serving size of the components of this diet needed to achieve these health benefits.      

Summarized from D’Alessandro et al., 2019

Origin of the Mediterranean diet

A study called Seven Countries Study of Cardiovascular Diseases began in the late 1950s and continued for some 50 years.  This seminal study tracked over 12,000 middle-aged men in North America, Northern Europe, and Southern Europe. It correlated dietary patterns with the incidence and mortality rates for coronary heart disease (CHD) and overall mortality (Menotti  and Puddu, 2015).  The striking findings showed that the incidence of CHD, other cardiovascular diseases and overall mortality was lower in southern Europe (Mediterranean countries and Japan) than anywhere else.  This improved health and longevity significantly correlated with decreased saturated fat consumption (low levels of serum cholesterol) and increased calorie intake from plant foods relative to animal meats.  In other words, this became known as the Mediterranean diet.

Proven benefits of the Mediterranean diet

There are numerous observational studies and clinical trials on the effects of adherence to the Mediterranean diet to health outcomes.  To make sense of the wealth of data, meta-analysis combines results from the  most rigorous studies to yield what are considered substantiated and valid conclusions.  The most recent of these meta analysis (Sofi et al., 2008; Dinu et al., 2018) evaluated 13 observational studies and 16 randomized clinical trials with regard to 37 different health outcomes. The results show adherence to the Mediterranean diet yields lower mortality for:

  1. Cardiovascular disease, Coronary heart disease, Heart attack
  2. Neurodegenerative diseases
  3. Cancers
  4. Diabetes
  5. All causes

However, there are limitations to studies assessing dietary patterns since they rely on validation of dietary questionnaires.  Hence, the need for the meta analysis that shows with a high degree of confidence that adherence to the Mediterranean diet compared to a non Mediterranean diet e.g. western diet, consistently yields valuable health benefits. 

Future – how the Mediterranean diet works

Several studies have endeavored to probe the underlying mechanism(s) of the Mediterranean diet on health benefits.  As a result, it has been shown, albeit in small studies, that the adherence to the Mediterranean diet for 6 months to one year lowers blood pressure (Davis et al., 2017; Jennings et al., 2019), improves dynamic blood flow (Davis et al., 2017), decreases proinflammatory mediators (Dyer et al., 2017) and reduces arterial stiffness (Jennings et al., 2019).

Other diets e.g. Okinawa, DASH and Portfolio will be discussed in my next blog.

ReferencesDownload