11 Ways To Increase Your Lifespan

Here are 11 ways to increase your lifespan by improving cellular function. As your cells age, so do you, so make them healthy.

Benefits of cellular autophagy

NEW YORK TIMES columnist Carl Zimmer makes the observation that although cells cannot fill out a census form, there are methods to approximate how many of them make up our bodies. Two methods are informed by weight and volume. You can go read the particulars, but suffice to say here that the weight method puts the number of cells at 70 trillion for a person weighing 70 kilogram (154 pounds), and the volume method gives an estimate of 15 trillion.

That’s a big difference, but for the purposes of this article, what matters is that the numbers are huge, and thereby, there’s the potential for a lot to go wrong.

And things do go wrong. In fact, several theories of aging focus on how and why various cellular functions go astray as we get long in the tooth.

This article is about what happens to our cells that are partly responsible for making us deteriorate, whether it be by the tried and true process of aging, or by malfunctions that give rise to various diseases, like cancer, diabetes, Alzheimer’s, as well as obesity.

Specifically, we’re going to learn about how to increase your lifespan by examining:

  • Cellular senescence, and
  • Cellular Autophagy.

Now, before you yawn and go check your email, know that if you stick around, read and watch what’s right here on this page, you will discover what you can begin today to make your life longer and healthier.


Let’s tackle this subject like this:

  • Read the descriptions below to get a sense for how senescence and autophagy are related to aging and health.
  • Watch the videos and read Dr. Watson’s “rundown” to learn about the new research that shows how we can reduce senescence and boost autophagy.
  • Finally, take a look at the 11 ways you can increase your cellular autophagy and thereby live longer and healthier. 


How Cellular Senescence Ages You

All of our multiple-trillion cells have built-in programming that is ever watchful for emerging conditions within them that could put the rest of the body at risk. Such conditions can be transformative, making the cell different – and problematic.

One important example is “senescent” cells. They begin their existence as skin cells, or as related cells that normally play supporting roles in other organs, but were forced into an abnormal state where they lost the ability to divide and reproduce themselves as a protective response to some danger.

For instance, the senescence program is activated in cells that undergo risky changes in their DNA expression that put them on a path toward becoming cancerous; it is also activated in some cells involved in the wound response, to keep them from overstepping their bounds and generating an overgrowth of fibrous connective tissue.  (1)

The number of these cells in our tissues gradually rises over time, until by our fifth decade they begin to reach levels that are harmful to normal tissue function. As the immune system becomes less effective, senescent cells build up and damage adjacent cells, causing chronic inflammation, which is closely associated with frailty and age-related diseases.

As you’ll soon see, we can take steps to minimize the deleterious effects of senescence, even if not a mouse.

Recently, researchers at the Mayo Clinic did just that – they increased the lifespan of mice as much as 35% by removing senescent cells, which, remember, are cells that no longer divide, and accumulate with age. They found that removing these aging cells delays tumor formation, preserves tissue and organ function, and extends lifespan without observed adverse effects. (2)

Watch Dr. Jan van Deursen describe how he and his team extended the lives of mice by injecting them with a compound called AP20187 to remove senescent cells, which delayed tumor formation and reduced age-related deterioration of several organs.

Watch and Learn How Senescent Cells Age You

2:35 A key finding is that senescent cells that accumulate are largely bad, do bad things to your organs and tissues and therefore you know shorten life.

4:47 A number of diseases that are occurring at very high rates in the population such as pulmonary fibrosis COPD, atherosclerosis, have in common an abnormal amount of senescent cells at the sites where the disease occurs.

5:58 One of the primary findings we observe was a very dramatic lifespan improvement in these animals, living roughly 25 to 35 percent longer than what the normal untreated mouse would be living. Not only do we have this extension in life span we also had an extension in their healthy lifespan so these animals seem to be prevented from having various age-related deterioration is happening in a variety of tissues with age.


Cellular Autophagy Can Reduce Senescence and More

Autophagy is the intracellular process that mediates the digestion of cellular components in lysosomes. The autophagic system fulfills two major functions in mammalian cells, serving both as an alternative source of energy, when nutrients are scarce, and as an efficient mechanism for the removal of any intracellular damage structure.

Autophagic activity has been described to decline with age in almost all organisms and tissues, as wells as in several age-related disorders. In light of the prevalent functions of this catabolic process, cells with impaired autophagy are often energetically compromised and present severe problems in maintenance of cellular homeostasis and in the response to stress. (3)

Mind you, cellular “stress” is not psychologically induced, as it may be for you as a person, but instead refers to anything that infringes on healthy cell function, such as oxidation, mitochondria electron “leakage”, DNA damage, protein damage, etc.

The relationship between senesce and autophagy is not fully understood. In fact, the title of a research report by Dr. David Gewirtz pretty much sums it up: Autophagy and senescence: a partnership in search of definition, wherein it says:

“The literature relating to this topic is inconclusive, with some reports appearing to be consistent with a direct relationship between autophagy and senescence and others indicative of an inverse relationship”. (4)

That was in 2013. An article published in Nature in 2016 announced a cause and effect relationship, which basically asserts that:

The regenerative functions of cells decline with age, leading to an irreversible senescence state. Autophagy can keep some of this from happening by reinstating in old cells their former capacity as young cells to maintain proper protein regulation (“proteostasis”), mitochondrial function and oxidative stress repair. (5)

A good rundown of the life extension potential and health benefits of autophagy is provided by provided by Dr. James Watson at Anti-aging Firewalls:

  • Autophagy is like having a Pac-man inside each of your cells that chases down, consumes and recycles dysfunctional organelles, proteins and protein aggregates.  It has three forms: (i) chaperone-mediated autophagy, (ii) microautophagy and (iii) macroautophagy, the most important.
  • Autophagy is a stress response and behaves according to the principles of hormesis.
  • Autophagy can retire and eat up old mitochondria that are “leaking” electrons.
  • Autophagy solves the problem of high baseline levels of reactive oxygen and nitrogen species.
  • Autophagy does not require proteins to be unfolded for it to work and therefore can perform housekeeping tasks undoable by the other cell-level house cleaning system, the ubiquitin-proteasome system.
  • Autophagy gets rid of the protein aggregates that can make you lose your memory or walk slowly as you grow old – those associated with Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, ALS, CTE, and other neurodegenerative conditions.
  • Autophagy keeps adult stem cells healthy and facilitates their capability to differentiate to make normal somatic body cells.
  • Autophagy prevents inflammation – it works hand-in-hand with apoptosis to help the body get rid of dying cells without inducing cell rupture and inflammation.
  • Autophagy prevents cancer – it helps maintain genetic stability, prevents epigenetic gene silencing.  And it helps promote oncogene-induced cellular senescence for cancer prevention.
  • Autophagy saves the lives of cells by preventing unnecessary cellular apoptosis and cell necrosis.
  • Autophagy is involved in Nrf2 activation and to some extent Nrf2 expression negatively regulates autophagy.
  • Autophagy keeps your bone marrow stem cell population alive and functional.
  • Autophagy helps with infections – it helps clear intracellular pathogens such as bacteria and viruses.
  • Autophagy improves the innate immune response.
  • While autophagy declines with aging, it can exercise multiple effects to slow aging down.  It inhibits the major mechanisms of aging such as cellular senescence, protein aggregate build-up, stem cell loss, epigenetic gene silencing, telomere shortening, and oxidative damage to proteins, lipids, and DNA.

OK, at this point you undoubtedly need a break from science-speak, so let’s turn to the next video in which Dr. Richard Gerhauser speaks plainly to us about what autophagy is, how it benefits us, and one simple way to make it happen.

Remember, we’re learning how to increase your lifespan, and health too, so don’t stop now.


11 Ways You Can Increase Your Cellular Autophagy and Live Longer and Healthier


In addition to the Intermittent Fasting (“IF”) regime that Dr. Gerhauser describes in the video — as I detail in Why Intermittent Fasting Is Your Ticket To A Long and Healthy Life there are a number of practical ways to promote autophagy, such as these, courtesy of Dr. Watson (6) :

  1. Fasting (in addition to IF) activates Autophagy – caloric restriction affects 5 molecular pathways that activate autophagy.
  2. Sunlight, Vitamin D and Klotho activate Autophagy – there are three ways through which UV light, Vitamin D, and the Klotho pathway activate autophagy via inhibiting the insulin/IGF-1 pathway.
  3. Rapamycin activates Autophagy – there are two ways through which mTOR inhibitors activate autophagy –  TORC1 and TORC2 mechanisms.
  4. Caffeine activates Autophagy – Caffeine can activate autophagy via an mTOR-dependent mechanism.
  5. Green tea activates Autophagy – ECGC can activate autophagy via an mTOR-dependent mechanism.
  6. Metformin activates Autophagy – metformin can activate autophagy via AMPK activation – mTOR-dependent and mTOR-independent mechanisms.
  7. Lithium activates Autophagy –  lithium and other compounds can activate autophagy by inhibiting inositol monophosphate and lower IP3 levels – an mTOR-independent mechanism
  8. Resveratrol activates Autophagy – there are four 4 ways through which resveratrol can activate autophagy – via mTOR-dependent and mTOR-independent mechanisms.
  9. Spermidine activates Autophagy – how spermidine activates autophagy via histone protein deacetylation – mTOR-independent mechanism.
  10. Hypoxia activates Autophagy –  intermittent hypoxia can increase autophagy via HIF-1a
  11. Phytosubstances which activate the Nrf2 pathway can activate Autophagy.  These are many and include soy products and hot chili peppers.


Your Takeaway

There’s a lot of science and unfamiliar terminology in this article, but among the ways to increase your lifespan and health that you really need to know about boil down to two things:

  1. A big part of why and how we age has to do with accumulated debris and uncorrected malfunctions that occur within our cells.
  2. There are certain foods, supplements, pharmaceuticals and activities that you can eat, take and do that can “clean up” the debris and correct the malfunctions, the most promising of which that is in your control is Intermittent Fasting.  Learn more about that in my article, Why Intermittent Fasting Is Your Ticket To A Long and Healthy Life.

Now, just in case one or two of you want to dive deeper into the science of autophagy, I leave you with a video by Dr. Ana Maria Cuervo from the Albert Einstein College of Medicine.



4:00 Deepening understanding of autophagy

4:50 Physiological and pathological processes

5:40 Functions of autophagy

7:00 Macro/micro autophagy intro

8:40 Macroautophagy detail

12:05 Chaperone-mediated autophagy (“CMA”)

13:00 Lysosomes and aging

14:27 Macroautophagy and aging

15:30 CMA and aging

17:20 Manipulating autophagy in worms and rodents

19:53 Repairing the autophagy processes

24:30 Restoration of CMA enables old mice to get rid of cumulated oxidized proteins

Last Updated on June 21, 2022 by Joe Garma

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Joe Garma

I help people live with more vitality and strength. I'm a big believer in sustainability, and am a bit nutty about optimizing my diet, supplements, hormones and exercise. To get exclusive Updates, tips and be on your way to a stronger, more youthful body, join my weekly Newsletter. You can also find me on LinkedIn, Twitter and Instagram.

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