Lifestyle Choices Do Slow Aging, Just Not as Much as We'd Like

In recent years, a number of epidemiological studies have demonstrated that people with healthier lifestyles tend to live longer, at least within the bounds of later life from 60 to 100. That in turn is reflected by a lesser burden of various forms of cell and tissue damage, such as the accumulation of senescent cells. This isn't a controversial statement, though there is room enough to argue for an eternity over just how large the effect of any specific choice might be, how that effect size varies between populations, how different choices combine, and so forth. Then on top of all of this, the question of what happens and why in extreme old age past 100 exists in its own realm of comparatively little data because of the low survival to such advanced ages.

Arguably we shouldn't much care about centenarians and the fine details of the various lifestyle and biological contributions to their survival odds, as it is much akin to asking why some people managed to die more slowly when infected with tuberculosis prior to the development of effective antibiotics. That question isn't the right focus for the problem. The right focus for aging is on the common root cause mechanisms that conspire to kill everyone, and on reversing those mechanisms such that no-one is killed by them. Understanding how some people manage to resist the cell and tissue damage of aging for a longer rather than a shorter span of years is irrelevant in comparison to understanding how to repair that damage.

The first rejuvenation therapies, in the form of first generation senolytics such as the dasatinib and quercetin combination, exist, are available to the adventurous, and are taking a surprisingly long time to emerge into a wider appreciation of their potential. The rest of the package of biotechnologies needed for human rejuvenation are going to take an appreciable amount of time to arrive in the clinic, perhaps several decades at this point, barring a major shift in the way in which medical regulation works. So if one can add a few years by making smarter lifestyle choices, then why not? It isn't any big secret as to what those choices are: regular exercise, strength training, calorie restriction of some form, and avoiding the many forms of readily available self-sabotage such as smoking.

Lifestyle interventions to delay senescence

Senescence is a condition of cell cycle arrest that increases inflammation and contributes to the development of chronic diseases in the aging human body. The beneficial role of senescent cells early in life can become detrimental in later years. The accumulation of senescent cells with time reduces the capacity of the body to regenerate and induces chronic inflammation via the senescence-associated secretory phenotype (SASP), which contributes to the condition of inflammaging during the aging process and especially in older adults. While senotherapies capable of clearing senescent cells have emerged as potential treatments for chronic diseases, less attention has been devoted to the effects of lifestyle interventions that are widely available, easy to implement, and safe when used as recommended.

Exercise is widely recognized to produce beneficial effects on health of animals and humans. Several preclinical studies indicate that exercise can reduce the number of senescent cells in various organs including the heart, liver, muscles, kidneys, and adipose tissues. For instance, wheel running for three weeks reduced the senescence marker p16 in the heart of mice. Aerobic treadmill exercise for 15-60 minutes daily, five times per week for six weeks reduced levels of senescence-associated beta-galactosidase in the kidneys of aged mice. Similarly, a three-month swimming program reduced senescence markers and the pro-inflammatory cytokine interleukin-6 (IL-6) in the liver of rodents treated with d-galactose to induce aging. However, the high heterogeneity of exercise regimens used in these animal models and the sole reliance on senescence markers limit our understanding of the mechanisms underlying the effects of exercise on senescence.

In humans, regular physical activity for at least 4 hours per month is associated with reduced levels of p16INK4 in T lymphocytes. A five-month training program reduced the number of p16INK4-positive senescent cells in thigh adipose tissues of older overweight women. Expression of p16 and IL-6 was elevated in the colonic mucosa of middle-aged and older overweight men compared to young sedentary men, whereas this elevation was blunted in age-matched endurance runners with several years of experience. Similarly, the increase of senescent endothelial cells and impaired vascular endothelial function observed in brachial arteries of older sedentary individuals was absent in older exercising subjects.

Different lifestyle interventions including exercise, nutrition, intermittent fasting, and consumption of phytochemicals, prebiotics and probiotics, and adequate sleep can produce anti-senescence effects in model organisms and humans. Given the widespread beneficial effects of these lifestyle interventions, the findings described here are perhaps not surprising - except that the reduction of senescent cells represents a new mechanism of action to explain the effects of these interventions. The effects of lifestyle factors on senescence are quite complex and can easily be neutralized or become detrimental depending on their intensity and frequency. Moreover, an unhealthy lifestyle involving sedentarity, consumption of excess alcohol, smoking, lack of sleep and sunlight exposure and chronic stress may offset some of the beneficial effects of other interventions on senescence. More attention should therefore be given to the modalities that produce beneficial effects and their interactions with anti-senescence compounds and other lifestyle habits.


"available to the adventurous" ? I guess we can get Quercitin in a pharmacy. But where can we get Dasatinib? In Catalonia it's only available in hospitals if you have cancer. If not, you can't buy it.

Posted by: Josep at November 14th, 2023 2:42 AM

@Josep: there are physicians in the US with anti-aging practices who prescribe dasatinib. Otherwise there are a few international organizations that will ship pharmaceuticals without requiring a prescription, as they are legally based in jurisdictions that simply don't care about such things. Otherwise, it can be ordered from manufacturers in China, somewhat harder today as Alibaba dropped pharmaceuticals, but one can infer which vendors to approach based on their other products, and the resulting delivery tested via a mass spectrometry service.

These options are of varying legality and odds of consequences depending on where you happen to be in the world, but if you morally object to the state of laws surrounding control of pharmaceuticals, then civil disobedience is always a choice.

Posted by: Reason at November 14th, 2023 4:07 AM

Thanks for your answer. I am 38. Do you think it's a good age to take D+Q? What dosage? Are you taking them? Thanks

Posted by: Josep at November 14th, 2023 8:24 AM

Josep, I bought Dasatinib 4 years ago from teamtlr, but they appear to be out of business. When I order again I am going to order from bonhoapharmacy. They may not ship to EU. I would not be taking Dasatinib until 50.

Posted by: JohnD at November 14th, 2023 8:30 AM

@Josep: I think one would have to go by what is currently known of senescent cell levels by age in humans. Some work has been published on this front:

I also am in the camp of not until 50-ish, probably, given what is presently known of senescent cells. Assuming one is not obese and basically healthy, or doesn't have a non-healing wound, or a joint issue that might possibly respond to senolytics.

As to dosage, that is all over the map. A physician has told me that they prescribe in old people a dose schedule to take place once every 6 months, taking 100mg dasatinib and 1000mg quecetin for five consecutive days. But if you look at the papers in mice and humans you'll see a great many other dosing schedules and amounts tested. I don't think anyone knows what is best, only that it should be intermittent.

Posted by: Reason at November 14th, 2023 8:36 AM
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