The work sets out reasons and strategies for attenuating the slow, seemingly inevitable decline in biological function that we call “aging.” The strategy doesn’t seek to tweak metabolism and uncover a silver bullet (sirtuin activators, anyone?) but rather to work around the complexity of metabolism by repairing the damage that increases with age.

The core impetus for targeting aging itself is that for the most prevalent Western diseases — heart disease, diabetes, cancer, dementia — the primary risk factor is age.

Governments and hence the private sector largely overlook this fact and do not recognize aging as a condition that can be alleviated medically. Thus little research funding flows toward what should be the focus of modern medicine, according to the authors.

The book is divided into three parts. Part I outlines why aging should be of paramount research interest. Part II explains, in terms accessible to an informed lay reader, the molecular mechanisms by which aging occur (and therapies designed to repair the damage) in Aubrey’s “Strategies for Engineered Negligible Senescence.” Part III puts forth a regulatory and research roadmap to establish a “Manhattan Project” for aging research.

—

Seven Deadly SENS

SRF has broken down the mechanisms aging into seven categories. These problems must be tackled, and proposed solutions are described in the book.

1. Cell loss and cell atrophy — Stem cells and tissue engineering

2. Nuclear (epi)mutations — WILT, short for "Whole-body Interdiction of Lengthening of Telomeres"

3. Mitochondrial mutations — Allotopic expression of 13 proteins

4. Death-resistant cells — Targeted removal

5. Extracellular crosslinks — AGE-breaking molecules and tissue engineering

6. Extracellular aggregates — Stimulating of the immune system to clear out the aggregates

7. Intracellular aggregates — Equipping the lysosome with enzymes capable of degrading the aggregates

—

Foundations of Rejuvenation

It is possible to alter cells in a petri dish such that they never stop dividing. Given the right conditions, human cells, like the notorious Henrietta Lacks “HeLa” cells, can life forever. These cells are “immortalized.” Cancer cells are often naturally immortalized by mutations of the gene encoding telomerase.

The vast majority of cells in body are replaced by stem cells regularly, from every seven days for skin cells to every seven years for bone. This rate of stem cell turnover declines with age. In light of these points, there is no apparent reason why the body could not rejuvenate itself indefinitely given the right stimuli.

It has been known since the 1930s that dietary restriction (DR) without malnutrition can dramatically slow the rate of aging, and since has been demonstrated in virtually all model organisms studied. Drugs seeking to mimic this effect are under development.

Somatic Cell Nuclear Transfer (therapeutic cloning) has been in vogue for over a decade. In 2008, cell therapy was revolutionized by a new method for generating induced pluripotent stem cells (iPSCs) from a sample of a patient’s skin. These cells could soon be sufficient to replace whole organs and potentially revitalize stem cell populations in vivo.

Recent Advances in Aging Research

This decade has witnessed the identification of genes governing aging and healthspan: insulin (daf-2, IGF-1), regulators of gene expression (FOXOs, sirtuins), and guardians of genomic stability and senescence (telomerase, HIF-1). Manipulating these genes can alter elements of the aging process and even reverse its progression. In recent years, more strategies have arisen. Just a few of the more prominent are listed below.

Heterochronic Parabiosis