Restore Youthful Cell Function via Autophagy

With age, the insides of our cells accumulate damaged proteins and other debris that impair youthful function.

Humans are equipped with a built-in process that removes these toxic waste products to make room for healthy internal regeneration.

This natural, cell housekeeping process is called autophagy.

Autophagy declines with age and poor diet,1 causing cells to be damaged at an increasing rate.2

Animal studies show that stimulating autophagy leads to improvements in healthspan and increased longevity.3-5

Scientists at Life Extension®, in collaboration with the Insilico Medicine research group, identified two plant extracts that stimulate autophagy.

What Is Autophagy?

Every cell in the body contains proteins and other components that serve vital metabolic purposes, from regulating cellular function to facilitating biochemical reactions.

When we are young, our internal cell machinery and its built-in cleaning process (autophagy) work at peak efficiency. This enables younger cells to clean up their metabolic waste.

The literal definition of autophagy is self-eating. In this process, the cell consumes and breaks down old cellular parts and debris.

This normal autophagy process supports healthy tissue function and promotes overall health.

But aging and poor diet contribute to lower rates of autophagy.1,4

As autophagy slows down, metabolic waste products and toxins accumulate. This slowdown compromises optimal cellular function.

The result is that cell health and function rapidly decline. This autophagy decline has been linked to many diseases of older age.4,6-10

Boosting Autophagy Extends Healthy Lifespan

In recent years, scientists investigating ways to maximize lifespan and reduce risk of chronic disease have increasingly focused on autophagy.4,6-9

In several animal studies, stimulating autophagy led to increased longevity.3-5

One study activated autophagy in mice by altering gene expression. The lifespan of these mice was extended by an average of 17.2%.5

This would be the equivalent of increasing the average human lifespan in the U.S. from 78.5 years to 92 years.

These animals didn’t just live longer. They were also healthier.

They maintained lower body weight than normal mice well into older age. They had increased insulin sensitivity, indicating improved metabolic health. And they had better physical functioning.

When the scientists inhibited the autophagy process, all these beneficial effects disappeared. That indicates that autophagy stimulation was the factor responsible for the health and longevity improvements.

Ways to Stimulate Autophagy

Research has shown that during times of intermittent fasting or caloric restriction, when nutrients are scarce, cells activate autophagy on their own.11,12

Physical exercise also stimulates autophagy.13

At a cellular level, two regulatory proteins play a key role in controlling autophagy: mTOR and AMPK.

The protein mTOR acts as a nutrient sensor. When caloric intake is high and nutrients are abundant, mTOR is activated and shuts off autophagy.14 Inhibiting excess mTOR activity, on the other hand, can lead to increased autophagy (removal of celluar waste).

Said differently, constant consumption of calories denies aging cells the ability of clean house via autophagy. Fasting 16-18 hours most days can facilitate autophagy, but most people need ancillary support in the form of drugs or nutrients that suppress excess mTOR.

AMPK is an activator of autophagy. Stimulating AMPK has been shown to improve metabolic health and lifespan.14-16

Using this knowledge, scientists set out to discover effective ways to stimulate autophagy.

Working with advanced artificial intelligence (AI) technology, they focused on two nutrients, luteolin and piperlongumine.

Each has been shown to induce autophagy individually via overlapping and distinct mechanisms.

Luteolin Protects Brain and Body

Luteolin belongs to the flavonoid group of plant nutrients. It is found in several fruits, vegetables, and herbs, including broccoli, parsley, and thyme.

Luteolin has been shown to both increase AMPK activity and inhibit mTOR signaling.17-20 The cumulative effect is that autophagy is activated, and cellular metabolism is improved.

In animals and cell culture, treatment with luteolin has been shown to protect the brain, heart, and tested cells.21-29

For example, animals with a brain injury fared better than their non-treated counterparts when given luteolin.27

Autophagy was activated, inflammation was reduced, and the overall outcome and recovery from the injury were improved.

Piperlongumine Keeps Cells Youthful

Piperlongumine is a compound isolated from the long pepper plant.

Like luteolin, piperlongumine has been shown in animal and cell-culture studies to activate autophagy by inhibiting mTOR signaling.30,31 There is also evidence that it activates AMPK.32

But piperlongumine encourages autophagy in another way that’s distinct from luteolin.

A protein known as beclin-1 is a critical activator of autophagy. Another protein, called Bcl-2, binds to beclin-1 and blocks its ability to start autophagy.

Piperlongumine causes the release of beclin-1 from Bcl-2, allowing it to activate autophagy.30

Luteolin and piperlongumine hold promise in maximizing healthy autophagy, rejuvenating cells, and maintaining their optimal function.

Summary

Autophagy declines with age and poor diet, causing cells to become overwhelmed by damage and metabolic waste at an increasing rate. This leads to accelerated aging and increased risk for chronic disease.

Stimulating autophagy can help prevent this slide into old age, improving the health and extending the lifespan of animals.

Scientists at the Insilico Medicine group in collaboration with Life Extension® have found two nutrients that activate autophagy: luteolin and piperlongumine.

In overlapping and distinct ways, they stimulate beneficial autophagy. Together, they can help keep cells functioning youthfully for improved health.

Material used with permission of Life Extension. All rights reserved.