• Barbara Johnson, MD

What causes us to grow older and succumb to ill health?

Updated: Feb 10


Most of us want to live into our 80’s and 90’s, as long as these years are spent in good health. Anti-aging researchers have made tremendous advances in not only understanding the aging process but also ways to slow it down and help us live longer and free from chronic disease.

What is Aging?

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. All of which progressively increase as we get older.

But the scientist still did not have a clear-cut definition of aging until recently.

The important milestone came in 2013, when a group of authors led by Carlos López-Otin, Professor of Biochemistry and Molecular Biology from the Universidad de Oviedo in Spain, published a landmark study called the Hallmarks of Aging in Cell. The paper has become one of the most widely-quoted and highly regarded papers in the scientific community and spurred many scientists to conquer the aging problem.

Aging research has experienced an unprecedented advance since this paper, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes.

The 9 Hallmarks of Aging

The 2013 study outlined the nine hallmarks of aging. These hallmarks are mostly cellular, as aging begins at the cellular level and then spreads to the tissues, muscles, joints, organs, and bones

Concomitantly, cellular damage may occasionally provide aberrant advantages to certain cells, which can eventually produce cancer. Therefore, cancer and aging can be regarded as two different manifestations of the same underlying process—namely, the accumulation of cellular damage.

Serrano, one of the lead authors of the paper, stated that this paper removes the "frivolity" with which aging research is often approached: "It's not about not having wrinkles or living to be a hundred at any cost, but about prolonging disease-free life." In Cell the scientists are explicit about their final goal, which is "to identify pharmaceutical targets to improve human health during aging."

"The current situation of aging research exhibits many parallels with that of cancer research in previous decades," reads the opening paragraph of the resulting paper, titled The Hallmarks of Aging. "The aging field has been notoriously more abundant in theories than experimental evidence," says Blasco; "this review doesn't discuss theories, but molecular and genetic evidence."

While different, the 9 hallmarks share a similar cellular time-dependent accumulation of cellular damage which is widely considered to be the general cause of aging.

Despite the interconnectedness between all hallmarks, the authors separated the nine molecular hallmarks of aging into a hierarchy: Principal Hallmarks, Antagonistic Hallmarks and Integrative hallmarks.

The Hierarchy of Aging

This hierarchy is important, because different effects can be achieved by acting on one or other of these processes. By acting on just one mechanism, if it numbers among the primaries, the aging of many organs and tissues can be delayed.

The 4 Principal Causes of Aging

These are the initiating triggers whose damaging consequences progressively accumulate with time. The hallmarks are not independent, and one often impacts the others. For instance, epigenetic alterations can affect protein stability, contributing to the hallmark of aging known as loss of proteostasis.

  • Genomic Instability

  • Telomere Shortening

  • Epigenetic Alterations

  • Loss of Proteostasis (Damaged Proteins)

The 3 Antagonistic Hallmarks

Called antagonistic because in principal are beneficial but can become progressively negative when promoted or accelerated by the primary hallmarks.

  • Deregulated Nutrient Sensing

  • Mitochondrial Dysfunction

  • Cellular Senescence

The 2 Integrative Hallmarks

These arise when the accumulated damage caused by the primary and antagonistic hallmarks cannot be compensated by tissue homeostatic mechanisms.

  • Stem Cell Exhaustion

  • Altered Intercellular Communication

Potential Therapies to Address the Hallmarks of Aging

In the published paper, Maria Blasco and her collaborators also provided areas of intervention that can be sought by science to help slow the aging process, deal with the present damage found, and prevent ongoing damage.

  1. The following areas of interventions are:

  2. Stem cell-based therapies

  3. Anti-inflammatory drugs, blood borne rejuvenation factors

  4. Elimination of Damaged Cells (Senescent Cells)

  5. Telemerase Reactivation

  6. Epigenetic Drugs

  7. Activation of Chaperones and Proteotic Systems

  8. Dietary Restrictions, mTOR inhibition, along with AMPK and Sirtuin Activation

  9. Mitohormetics, Mitophagy

  10. Clearance of Senescent Cells,

This 2013 paper has spurred a new breed of geroscientists who have made progress in many areas and are actively working on pharamceuticals that address the above therapies. Dr. David Sinclair, at Harvard, has been working in the field of aging for over 20 years and the work coming out of his lab is prolific and relevant. His experiments are looking beyond the 9 hallmarks of aging and into reversing the aging process. Ongoing clinical trials are looking at ways of restoring the body’s DNA repair mechanisms using NAD boosters.

What Can You Do Today?

The projection is that within the next 10 years, pharmaceuticals addressing these Hallmarks of Aging will be on the market. What you need to do today is take a deep dive into your molecular health by looking at blood markers, organic acids and urinary toxins. You can start to stall and reverse as many contributing factors as possible, but you do have to test. Once you know your biochemistry and toxic exposure you can start working on healing and improving your longevity. This can be done with targeted lifestyle changes, supplements and prescriptions if needed.


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