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.

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.