Living longer and living more years looking and feeling youthful and disease-free are not one and the same. Although our life expectancies are getting longer, people are also spending more years with age-related chronic diseases. That is to say, we are not necessarily getting more years of vitality and good health but instead are getting to experience more years of illness.

With major advances in sequencing technologies and analytical algorithms, the ability to define aging and longevity separately has become possible only in recent years. These definitions are essential for improving aging and longevity and living longer lives filled with lots of energy and good health.

Know thy enemy, and know thyself

One way to think about aging and longevity is in terms of healthspan and lifespan, respectively:

  • Healthspan: the part of a person’s life during which they are generally in good health.
  • Lifespan: the time a person or animal lives.

With these concepts in mind, the scientific community has come up with some general definitions for aging and longevity, which can be roughly stated as the following:

  • Aging: the progressive, event-dependent decline in the ability to maintain biochemical and physiological function.
  • Longevity: the length of the lifespan.

Now, just because these two concepts are different doesn’t mean they are not intertwined. Distinguishing human biological aging from longevity can be difficult because the rate of aging may affect the length of the lifespan. With that being said, some researchers argue that lifespan and longevity are independent of healthspan and aging. That is to say, there are different forces at play.

The forces driving aging and longevity

Researchers have demonstrated with complex mathematics that longevity is determined from evolutionarily selected genes for reproductive advantage (i.e., survival of the fittest). Human longevity should best be thought of as an accidental byproduct of fixed genetic programs that optimize growth, development, reproduction, and ensure offspring’s reproductive success, such as grandparenthood.

On the other hand, aging is driven by a balance of damage and repair processes, influenced by environmental exposures and genetic variation. There is genetic evidence for the importance of several damage pathways in humans. Damage can be intrinsic, for example, through non-reproductive cell mutations arising during cell division. Also important are health behavioral risk factors such as smoking and obesity, which are also influenced by gene-environment interactions. The net impact of damage depends on the activity of repair and response mechanisms. At the cellular level, complete repair can yield undamaged cells.

By contrast, unrepaired damage can lead to cell death (apoptosis), preventing cancers but leading to the depletion of stem cells and loss of regenerative capacity. Cells with somatic oncogene mutations can survive and replicate, sometimes leading to tumor development. Alternatively, damaged cells can enter senescent states and produce a secretory senescence phenotype (SASP), resulting in inflammation and reduced repair that contributes to degenerative diseases. These mechanisms can result in reduced repair and increasing incidence of chronic diseases of aging but with decreased cancer risks, or vice versa.

Limits to aging and longevity

The rise in human longevity is one of humanity’s crowning achievements. Although advances in public health beginning in the 19th century initiated the rise in life expectancy, recent gains have been achieved by reducing death rates at middle and older ages. A debate about the future course of life expectancy has been ongoing for the last quarter-century.

(Olshansky 2021 | Nature Aging) Age distribution of death in developed nations. The red zone depicts the increased rate of frailty and disability in old ages.

Some suggest that historical trends in longevity will continue and radical life extension is either visible on the near horizon or has already arrived. Others propose that there are biologically based limits to the duration of life, and those limits are being approached now. A growing compilation of research is starting to point towards there being limits to human longevity. Observed mortality trends in the United States since 1990 indicate definitively that the rate of improvement in life expectancy in the United States has decelerated dramatically.

(Olshansky and Carnes 2019 | J Gerontol A Biol Sci Med Sci. )
Annual Average Rate of Improvement in Life Expectancy at Birth by Decade (United States, 1990–2016)

So, predictions of radical life extension just by boosting lifespan independent of healthspan are unlikely to be forthcoming. That suggests that there may be a greater benefit to aging and longevity if the primary goal of medicine and public health is to focus on healthspan extension instead of thinking purely of lifespan extension. Promoting advances in aging biology may allow humanity to break through biological barriers that influence both healthspan and lifespan, allowing for a welcome extension of the period of healthy life, a compression of morbidity, but only a marginal further increase in life expectancy.

We shall overcome

In the coming years, much more will be learned about human aging. With larger studies surveying the DNA sequences and gene regulation will capture more of the genetic variation between individuals and help identify the mechanisms of the effect of these genetic variations. It seems probable that much more evidence of aging pathways will be found, including novel pathways that could provide intervention targets or offer new prevention opportunities.

There remains ample scope for using inherited variants to understand human aging mechanisms. Overall, human genetics will likely continue to provide growing insights into how we age and play a major role in identifying ways to slow aging, thus helping more people to age well and hopefully experience happier and more fulfilling lives.