01Scientific Definition

Age-related diseases are diseases that occur with increased incidence associated with aging. Common age-related diseases include Alzheimer’s Disease, Chronic obstructive pulmonary disease, Maculopathy, Osteoarthritis, Osteopenia, Parkinson’s Disease, Periodontitis, Rheumatoid Arthritis, and Sarcopenia.

02The Longevity Connection

Some longevity scientists consider that extending healthspan - in other words, fighting age-related diseases - is the most straightforward strategy to extend lifespan. It’s also important to keep in mind that the prevention and treatment of diseases associated with aging is, of course, a great path for preserving quality of life in advanced years.

01Scientific Definition

Biological age is a concept that refers to the aging that occurs from the accumulation of cell and tissue damage throughout the body. When determining one’s biological age, many factors may be taken into consideration, including protein and DNA methylation markers. Unlike our chronological age, which is defined as the time that has passed at any given moment since our birth, biological age varies among different people (with a deceleration in people with healthy habits and an acceleration in people with unhealthy habits), and can even be reversed!

02The Longevity Connection

Longevity scientists are interested in studying biological aging. We explore lifestyle and genetic factors that contribute to the accumulation of cell damage in our organs, and its impact on the body. To combat the effects of biological aging, we are dedicated to discovering technologies that target cell damage, with the objective to delay the onset of cellular senescence and age-related disease. Our main objective at OneSkin (shared across the longevity field!) is to reverse biological aging, as shown possible in studies involving a small number of participants (Fahy et al., Aging Cell, 2019).

01Scientific Definition

Regions of the world where inhabitants have the lowest rates of chronic disease and live the longest. Author and National Geographic Fellow, Dan Buettner, coined the term ‘Blue Zones’ while studying areas in the world in which people live the longest. In his book, The Blue Zones, Buettner identifies the following five regions as Blue Zones:

• Okinawa, Japan
• Sardinia, Italy
• Nicoya, Costa Rica
• Ikaria, Greece
• Loma Linda, California

02The Longevity Connection

Longevity scientists like ourselves are fascinated with the genetic and lifestyle traits of those living in Blue Zones. We study how inhabitants of these regions live their lives in ways that differ from others, and what learnings we can incorporate from them to optimize our healthspan.

01Scientific Definition

A diet that reduces one’s average daily caloric intake, without leading to malnutrition or deprivation of essential nutrients.

02The Longevity Connection

Calorie Restriction Diets have been investigated for nearly 100 years as strategies to extend a person's healthspan and lifespan. Accumulated evidence points towards the efficacy of such diets, according to research across multiple model organisms including flies, mice, and primates. In such animals, the reduction of 10 to 40% of daily caloric intake for certain time periods (without resulting in malnutrition) was associated with a lower incidence of age-related diseases, such as cancer, and longer life. The evidence in humans is less clear than with other organisms, largely because humans have long lifespans, and our lifestyle factors are influential in producing outcomes.

01Scientific Definition

The concept of cellular senescence is still in evolution, but is considered a natural, biological process, likely elected throughout evolution due to its importance in embryonic development, wound healing and tumour suppression. The most notable characteristic of cellular senescence is the irreversible cessation of cell division and replication.

02The Longevity Connection

Throughout the aging process, old cells are constantly dying and being cleared away in order to make room for new, healthy cells. As we age, the rate at which our cells are able to divide and replicate continuously decreases until eventually, they stop replicating entirely. Some old cells die, but others are resistant to cell death (apoptosis) and become senescent. Ideally, senescent cells are cleared by our immune system, but with age, our immune system becomes increasingly less efficient at doing so, resulting in the accumulation of senescent cells throughout our bodily tissues and organs.

Senescent cells release pro-aging and inflammatory signals to their neighboring healthy cells, which negatively impacts their environment. This negative environment can then influence healthy cells towards senescence, further driving the buildup of more senescent cells. The build-up of senescent cells drives inflammation, resulting in numerous symptoms of age-related diseases, and can contribute to cancer.

01Scientific Definition

The dermis is the second layer of skin, and lies below the epidermis and above the hypodermis. The dermis is composed of connective tissue, hair follicles, blood vessels, lymphatic vessels, and sweat glands.

02The Longevity Connection

The dermis provides the epidermis with oxygen and nutrients. Naturally occurring molecules in the dermis associated with hydration (e.g. glycosaminoglycans and hyaluronic acid), structure (e.g. different types of collagen), and elasticity (elastic fibers) are reduced with age. This results in decreased dermal thickness, as well as a less effective interaction with the epidermis which compromises epidermis health and renewal. Scientists argue that visible wrinkles are the outcome of atrophy and changes that occur in the dermis.

01Scientific Definition

Visible to the eye, the epidermis is the outermost layer of the three layers that make up the skin, overlying the dermis and hypodermis.

02The Longevity Connection

With age, we experience a reduction in our epidermal thickness. This is why older people often bruise easily and take longer to heal. Epidermal thickness plays an important role in our health, as it protects us from external threats. A general rule of thumb is that the thicker the epidermis, the more protection you have (which is why we’re evangelical about taking care of your skin!).

01Scientific Definition

Scientists have not come to an agreement when it comes to defining epigenetics, but following the current concept published by the National Human Genome Research Institute of the NIH, epigenome is defined as all chemical modifications of DNA in a given cell, which does not alter the DNA sequence (A, T, C, G), but affect gene expression.

02The Longevity Connection

When we age, our epigenomes suffer predictable modifications, which strongly correlate with the passage of time and the health status of the organism or organ. Therefore, the study of a person's epigenome provides scientists with very accurate information about the biological age of a person or specific organ.

01Scientific Definition

The literal meaning of geroprotector is a drug or intervention that protects against aging, meaning that it will extend your life.

02The Longevity Connection

The term geroprotector, first used by the Nobel laureate Ilya Mechnikov in 1910, refers to molecules or interventions that extend lifespan. Therefore, those are the molecules searched by scientists in the field of aging. Senolytics, senomorphics, senostatics, and other molecules are types of geroprotectors. Currently, it is proposed that geroprotectors meet 8 requirements, including the following:

• To effectively increase lifespan
• To lead organs, tissues, or the organism as a whole to a younger state or slow the progression of age-related change in these sites
• To be safe and non-toxic
• To improve health-related quality of life at the physical, mental, emotional and social level

Other requirements are found to be effective in different species, to treat different age-related disorders, and to increase specific organism resilience.

01Scientific Definition

The period of life spent in good health, free from chronic disease, and disabilities of aging.

02The Longevity Connection

Modern medicine places significant importance on the extension of lifespan, yet most individuals want to age with grace and good health, suggesting that quality of life is much more important. Faced with this dilemma, longevity scientists like ourselves are dedicated to studying measures that can extend the healthy, high-quality portion of human life.

Interestingly enough, the average American has a lifespan of 79 years, but an average healthspan of 63 years. This means that an American spends almost 16 years (20%) of one’s lifespan living with disease.

If you want to ensure a healthy AND high quality of life, research suggests that lifestyle factors play an integral role in promoting healthspan. Aim to use the recommendations below as a general guide to kick-off healthy habits:

• Abstain from smoking
• Engage in regular physical movement
• Consume a healthy diet composed largely of fruits, nuts, vegetables, whole grains, fish and dairy
• Maintain strong social networks, psychological support systems, and allow for opportunities to engage in human interaction
• Develop coping mechanisms to aid in stress relief
• Practice periodic fasting

01Scientific Definition

The hypodermis is the innermost layer of the skin, lying below the epidermis and dermis. The hypodermis is mainly composed of fat and connective tissue (helping to shape our bodies), and its most remarkable function is insulating our body which prevents us from losing heat and minimizes shock absorption from external forces. A less mentioned, but equally important function of the hypodermis is its role in the secretion of the hormone leptin, which together with adipose cells, signals to our body to stop eating once we are satiated.

02The Longevity Connection

Even though the hypodermis is the deepest layer of the skin, it is responsible for skin sagging during aging. The hypodermis tends to become thinner with age, which leads to volume loss of the skin.

01Scientific Definition

Age-related inflammation, dissociated to any specific disease.

02The Longevity Connection

It has been observed that pro-inflammatory molecules are frequently more abundant in aged organisms than in younger counterparts. Similarly, elders are more prone to infection and respond less effectively to vaccination. Such deregulation and inefficiency of the aged immune system are termed inflammaging. Despite the fact that the cause of this state has not been completely established at this point, several different processes seem to promote inflammaging.

The weaker barrier of the skin and intestine, for instance, seem to make it easier for microorganisms to enter our body, promoting inflammation; furthermore, the accumulation of damaged cells also induce immune response in our bodies. Finally, the excessive inflammatory signaling caused by the two cited processes, added to the senescence of the immune cells also contribute to the immune system deregulation during aging.

Currently, seven interconnected pillars have been proposed to explain inflammaging, namely: excessive inflammation, low stem cell regeneration, accumulated macromolecular damage, stress, deregulation in protein metabolism, altered organismal metabolism, and epigenetics. Since the immune system is essential for organismal health, it is paramount to fight inflammaging in order to achieve healthy aging.

01Scientific Definition

A diet that focuses on controlling when you eat, rather than what you eat. Intermittent fasting follows a pattern that cycles between times of eating and fasting, and doesn`t necessarily result in reduced caloric intake.

02The Longevity Connection

Intermittent fasting can be executed in several different regimens, such as a 16-hour fasting and 8-hour feeding cycle every day, or the 5:2 method where two days of the week one consumes only 500 calories. Interestingly, it appears that the beneficial effects promoted by intermittent fasting in human health occur regardless of weight loss, suggesting that the metabolic effects of fasting trigger health benefits even in the absence of caloric restriction. The exciting aspect of this finding is that by discovering such metabolic and signaling effects that fasting brings about in the body, we may mimic intermittent fasting through fasting-mimicking diets or even nutraceuticals or pharmaceuticals.

01Scientific Definition

Metformin is an FDA-approved drug currently being prescribed for type 2 diabetic patients. It has several different commercial names, including Fortamet, Glucophage, Glucophage XR, Glumetza, and Riomet.

02The Longevity Connection

Metformin has been proposed to be a geroprotector, since studies with animal models and also retrospective data on beneficial health outcomes have shown promising results. Current data suggest that humans who continuously use metformin to treat type 2 diabetes tend to live longer than age-matched counterparts. This has led some doctors to prescribe the drug off-label, so their patients could benefit from its purported “anti-aging” effects. It’s important to note, however, that the use of metformin to delay the onset of age-related diseases and conditions including cancer, cardiovascular disease and Alzheimer’s disease, is not well established, with no definite results.

01Scientific Definition

The microbiome refers to all the genetic data of microorganisms found in a specific environment in or on the body.

02The Longevity Connection

The study of any given microbiota is often executed through the analysis of the microbiome. Since there are numerous unique environments of microbiota that are modulated with age, interest in the microbiome has sparked increased study by longevity scientists.

01Scientific Definition

Research has shown that during aging, our cells present alterations in their DNA methylation pattern. In humans, many labs have used the patterning of DNA alterations to correlate an individual’s chronological age and health status, therefore constituting a reliable parameter to quantify biological aging.

02The Longevity Connection

Longevity scientists are interested in studying biological aging. Currently, their main strategy is to analyze the molecular DNA age of blood or even specific organs, which correlates with organismal health and accumulated damage. Interestingly, each tissue in our bodies follows a unique aging process, which is what inspired us at OneSkin to develop a skin-specific aging algorithm to calculate the molecular DNA age of skin in humans.

01Scientific Definition

This interesting little mammal, Heterocephalus glaber, is neither a mole nor a rat, and has been utilized as a model organism to study aging due to its extraordinarily low cases of disease, and that it is not more likely to die as it ages (therefore it has the same chance of dying at age one that it does at age 25). One of the most interesting aspects of naked mole-rats’ physiology is their resistance to cancer, which is due to their increased production of very large hyaluronic acid molecules in their skin.

02The Longevity Connection

The naked mole-rat is a source of tremendous study (and mystery!) among our longevity scientist peers. We are interested in learning how the naked mole-rat has adapted to live without any increased risk of death with age, and how they seem largely immune to disease. Some of us at the OneSkin team even think they’re cute, but we’ll let you decide on that!

01Scientific Definition

Rapamycin is an FDA-approved drug currently indicated as an immunosuppressant to prevent organ rejection in patients who received organ transplants. It is commercialized in the USA under the commercial name of Rapamune.

02The Longevity Connection

Rapamycin was the first FDA-approved drug identified by the National Institutes of Aging as capable of extending the lifespan of both male and female mammals. Rapamycin has been one of the best studied geroprotectors, and a reference molecule in aging studies. Even though its life extension effect has never been formally tested in healthy humans, some effects over specific diseases and the immune system have been investigated in clinical studies. Despite promising results, rapamycin has shown concerning adverse effects, so strategies to prevent them are underway, including intermittent use of the drug and the investigation of rapalogs, which are biosimilars of rapamycin.

01Scientific Definition

A class of molecules thought to selectively induce death of senescent cells with the goal of prolonging longevity in humans.

02The Longevity Connection

The use of senolytics is a potential strategy to eliminate the body’s senescent cells to treat age-related disease and to promote longevity. Currently, many senolytics are in clinical trials, including both naturally occurring molecules and synthetic molecules, and currently no senolytic is commercially available. Since aging is not yet recognized as a disease, the current indications of the senolytics under investigation are age-related diseases, such as osteoarthritis and neurodegenerative diseases.