Scientists group the biology of aging into 12 hallmarks, such as DNA damage, shortening telomeres, failing mitochondria and chronic inflammation. They are interconnected, and most of the evidence that targeting them slows aging comes from animal studies, not people.
We age because damage and wear accumulate in our cells and tissues over time, and the systems that repair, recycle and coordinate them gradually lose ground. Scientists organize these processes into "hallmarks of aging," a framework first published in 2013 with nine hallmarks and expanded in 2023 to twelve. The hallmarks are interconnected rather than separate causes, and while experiments in laboratory animals show that some can be slowed, evidence that targeting them changes how people age is still limited.
In the 2013 Cell review that introduced the framework, López-Otín and colleagues defined aging as a progressive loss of physiological integrity that leads to impaired function and increased vulnerability to death. They proposed that each hallmark should ideally meet three criteria:
The authors were candid that the third criterion is the hardest to meet, and that not every hallmark is yet supported by interventions that slow aging.
The 2023 update lists genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation and dysbiosis. It groups them into three categories, building on the 2013 grouping.
The 2013 review describes these as unequivocally negative.
The 2013 review explains that these responses protect the body at low levels but become damaging when exaggerated or chronic.
The 2023 authors stress that the hallmarks are interconnected with each other, so the categories are a way to organize thinking, not separate boxes.
Several hallmarks connect to NAD+, a coenzyme central to energy metabolism. A 2021 review by Covarrubias and colleagues in Nature Reviews Molecular Cell Biology explains that NAD+ influences metabolic pathways, DNA repair, chromatin remodeling, cellular senescence and immune cell function, which touch nutrient sensing, mitochondrial function, genomic stability and senescence. The review reports that NAD+ levels decline gradually with age in multiple species, including humans.
The same review is careful to add that much remains to be learned, including how to restore NAD+ effectively during aging, whether doing so is safe, and whether it benefits aging humans. NAD+ injections, including those available through NewDay Wellness, are compounded and not FDA-approved, and they have not been shown to slow any hallmark of aging in people. For the evidence by delivery route, see NAD+ nasal spray, injection and IV compared.
A 2014 Cell article from a trans-NIH Geroscience Interest Group summit, by Kennedy and colleagues, makes the central argument for this field: aging is the greatest risk factor for a majority of chronic diseases, and mammalian aging can be delayed with genetic, dietary and pharmacologic approaches in experimental settings. If shared aging processes underlie many diseases, then slowing those processes could delay several diseases at once. The authors called for research directed at extending human healthspan, the years lived in good health.
Most hallmark research comes from cells and laboratory animals, and results do not always translate to people. Human trials that try to slow aging directly are few, and they rely on indirect measures. One example is the CALERIE trial, in which 220 adults without obesity were randomly assigned to calorie restriction or their usual diet for two years. A 2023 analysis by Waziry and colleagues found that calorie restriction slowed one DNA methylation measure of the pace of aging by an estimated 2 to 3 percent but did not change two other aging clocks. The authors noted that a conclusive test will require long-term trials measuring chronic disease and mortality.
No single hallmark has been shown to drive aging on its own. The 2023 review emphasizes that the hallmarks are interconnected, so a change in one can affect others, and researchers are still working out their relative contributions.
In laboratory animals, genetic, dietary and drug approaches have delayed aging. In people, evidence is early and indirect, so it makes sense to focus on well-established habits such as staying active, eating well and not smoking, and to discuss any longevity therapy with a licensed provider.
They can be interesting, but they are best interpreted with a licensed provider alongside standard health measures. Our guide to biological age vs. chronological age explains what aging clocks can and cannot tell you.
No human trial has shown that. NAD+ is involved in several processes linked to the hallmarks of aging, and its levels decline with age, but a 2021 review notes it is still unknown whether restoring NAD+ benefits aging humans.
The hallmarks of aging explain why risk for many conditions rises with age, but they do not replace individual care. A licensed provider can review your health history, prioritize proven preventive steps, and discuss what is and is not known about newer longevity therapies. This article is educational and does not determine eligibility for any treatment.
Written by the NewDay Wellness editorial team from the sources above and checked against them before publication, and medically reviewed by Dr. Sean Arora and Dr. Shannon Arora of Arora Health & Aesthetics; see our editorial standards. This article is educational and does not diagnose conditions, establish eligibility for any medication, or replace care from a licensed provider. Compounded medications are not FDA-approved.
NAD+ can be given by IV infusion, injection under the skin or nasal spray, but human data on these routes are small, short and mostly limited to blood levels and tolerability. No route has been shown to improve health outcomes in controlled trials.
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