The Treasure in the Strawberry

A third senolytic component of natural origin has also been discovered: piperlongumine. It occurs in concentrated form in a spice that is typically sold in Indian grocery stores as pippali (piper longum, also known in China as pibo and in Europe as long pepper). What it is and what it can do, I explain in see.nf/pippali. It convinced me so much that I added it, together with amla, black cumin, and turmeric, to my daily spices. Note that consuming pippali during pregnancy and breastfeeding is not recommended.

Food for Thought

Cellular senescence is one of the fundamental hallmarks of aging. The pro-inflammatory SASP secreted by senescent cells is considered a main driver of tissue degeneration and disease. To prevent cellular senescence in the first place, we can avoid DNA damage by following the recommendations in the chapter on oxidation and—and to help eliminate such cells along with their SASP—use the natural senolytic components in foods: quercetin, fisetin, and piperlongumine. Although it is not yet clear whether eating foods with these components can achieve a sufficient level, these foods are healthy in their own right.

To help slow down this pathway of aging, you should daily:

Epigenetics

Until recently, the aging process was viewed as irreversible decay, characterized by the increasing accumulation of molecular damage to key components of cells, especially DNA. Just as car parts wear out over time, so do the parts of our bodies. Yet there have always been life forms that contradicted this assumption, apparently defying age by falling into a kind of suspended animation. For example, date pits unearthed in archaeological excavations germinated after thousands of years; plants grew from fruits that Arctic ground squirrels had buried 30 000 years ago; and bacterial spores remained viable after being trapped in amber for multiple tens of millions of years or preserved in salt crystals for millions of years. But you don’t need exotic examples to demonstrate that biological age can become decoupled from chronological ("calendar") age. Cases in which the clock of aging is not only stopped but actively turned back—and even reset to zero—happen every day.

The Great Reset

Think about it. A female baby is born with all the eggs she will ever have. It can take decades for one of them to be fertilized. That egg could sit in the ovaries for 20, 30, 40 years—and age like all other body cells. Say the woman becomes pregnant at 30. If this 30-year-old egg does not somehow reset its aging clock to zero at fertilization, it could lead to the birth of another little girl whose ovaries would then be 30 years and nine months old. If that girl then gave birth decades later, the eggs would be over 50 years old and would keep aging, accumulating molecular damage with each generation. That is why all signs of aging in egg cells must be eliminated. Otherwise, the eggs in women’s ovaries would be millions of years old!

In 1996, we learned that egg cells are not the only ones that can undergo a complete reversal of aging. That year, a sheep named Dolly was born. The nucleus of an unfertilized egg had been removed and replaced with the nucleus of an udder cell. ("Dolly comes from a mammary gland cell," said one of the lead researchers unabashedly to explain where she got her name, "and we couldn’t think of more impressive mammary glands than Dolly Parton’s.") Then, triggered by a mild electrical impulse, the cell began to divide—without sperm—and Dolly, the first animal cloned from an adult cell, was born. (A frog had previously been cloned from a tadpole cell, which earned the researcher the Nobel Prize, but Dolly was the first animal cloned from the cell of an adult animal.)

The world marveled that a genetically identical duplicate of an animal could be created. Since Dolly, thousands of clones of mice, goats, pigs, rats, cows, horses, ferrets, wolves, deer, buffalo, camels, and dogs have been produced. Also cats, the first of which received the predictable name "Copycat." The implications go much further, however, than duplicating especially productive farm animals or generating Fido 2.0. In this single, mature cell specialized for milk production was the complete genetic blueprint for the entire animal we would come to know as Dolly. What’s more, the age of the cell appeared to have been reset to zero.

A persistent misconception holds that Dolly suffered from some sort of premature aging syndrome. After all, sheep live to about twelve years; the udder cell was taken from a six-year-old animal; and Dolly died at six, which would suggest that the aging clock had simply kept ticking without being reset. But Dolly died of a viral disease, not of old age, and subsequent experience shows that clones can have a normal lifespan. In fact, mice have been cloned in series—that is, there were clones of clones of clones, over 25 generations—and all aged normally in terms of lifespan. So not only can adult cells be reset to the embryonic state, they can be effectively rejuvenated by wiping away all traces of aging.

Welcome to epigenetics!

Genes load the gun, but lifestyle pulls the trigger

The term "epigenetics" was coined in the 1940s, before we even knew the physical nature of genes—a full decade before Watson and Crick (and Wilkins and Franklin) solved the mystery of the structure of DNA. Epigenetics, literally "beyond genetics," layers an additional level of information on top of the DNA sequence, which by itself amounts to only about 750 megabytes of data and encodes 50 000 genes. All somatic cells are genetically identical and contain a complete set of our DNA, but not every cell has to express all of our tens of thousands of genes. Nerve cells don’t need to produce liver enzymes, and heart cells don’t need to grow hair. That’s where epigenetics comes in—it is what turns genes on and off.

Our bodies do this in various ways. I cover sirtuins and microRNAs in their own chapters, but the best-known epigenetic regulator is DNA methylation.

We have enzymes that can strategically attach methyl groups directly to DNA to silence gene expression. A methyl group is a simple, stable carbon compound that can be added onto DNA to indicate that sections of it can be skipped. This is one of more than a dozen ways DNA can be marked. We also have enzymes that remove these markings and can turn the gene back on. Along our genetic code are about 28 million common methylation sites, most of which get methylated at some point. When cells divide, the methylation pattern is preserved—so, for example, a liver cell divides into two new liver cells and not into a bone or muscle cell—and in this way methylation patterns in sperm and eggs can be passed down across generations.