Most people think aging is something that happens later.

In reality, the processes that determine how you age — and whether you stay functional — start decades earlier.

In this episode of Return on Health, we sit down with Roberta Vella Azzopardi, a geriatrician and geroscientist with a PhD in cognitive frailty, to break down what aging actually looks like in clinical practice.

Instead of focusing on single diseases, this conversation zooms out: Why do people lose independence? What really drives decline? And where are the biggest missed opportunities in prevention?

What this episode covers

• Why modern medicine often intervenes too late
• What frailty really means — and why it matters more than age
• How loss of muscle drives metabolic and cognitive decline
• The concept of peak span and why function beats lifespan
• Why hearing loss is one of the biggest overlooked dementia risk factors
• The massive gap in menopause and women’s health care
• What actually works vs. what’s just hype in longevity

Key takeaways

Frailty is best understood as loss of physiological reserves.
When those reserves drop below a certain threshold, even small stressors can lead to long-term decline.

This is why two people at the same age can look completely different clinically — one independent, one dependent.

A major driver of this process is muscle loss.
Muscle is not just about movement. It directly affects metabolic health, insulin sensitivity, and even brain function. The good news: even later in life, resistance training and sufficient protein intake can still improve outcomes.

One of the most underestimated risk factors discussed in this episode is hearing loss.
It contributes to cognitive decline through increased cognitive load, social isolation, and shared vascular mechanisms — yet remains widely underdiagnosed and undertreated.

Another critical blind spot is women’s health, especially around menopause.
Many symptoms are treated in isolation instead of addressing underlying hormonal changes, leading to years of missed intervention opportunities.

Timestamps

(00:00) Introduction & Roberta’s background
(04:30) Frailty explained: vulnerability vs. age
(11:00) Why prevention starts decades earlier
(16:50) Reversing decline: muscle, protein, training
(21:00) Peak span vs. lifespan
(28:30) Menopause and missed diagnoses
(36:30) Dementia prevention & modifiable risks
(37:00) Hearing loss and cognitive decline
(50:00) Busting common aging myths
(55:00) Lightning round insights

Takeaways

• Start investing in your health early — not when problems appear
• Maintain muscle mass through resistance training and protein intake
• Don’t ignore hearing health — it directly impacts brain health
• Look at root causes, not isolated symptoms
• Prevention is not one intervention — it’s a system

Roberta:
https://www.linkedin.com/in/roberta-vella-azzopardi-md-phd-8235878a/

Return on Health:
https://returnonhealth.de/

Niko:
https://www.linkedin.com/in/niko-hems/
https://www.instagram.com/niko_hems
https://nikohems.de/

Miguel:
https://www.linkedin.com/in/miguel-medina-stanivukovic-857b9720b/
https://www.instagram.com/miguelmedinastanivukovic/?hl=en

Karolinska MD PhD: You Feel Healthy. Your Data Disagrees

Most people think they’re healthy.

But biology doesn’t care how you feel.

Long before symptoms show up, your physiology is already shifting.. and most check-ups won’t catch it.

In this episode, we sit down with Natalia Trpchevska (MD, PhD Karolinska, Medical & Scientific Director at AYUN) to break down what longevity medicine actually looks like when applied properly.

We go beyond surface-level optimization and talk about what actually drives risk: mitochondria, metabolic flexibility, genetics, and why most people are already off track without knowing it.

This episode covers:

• Why longevity medicine still struggles in practice
• Mitochondria, NAD+ and optimization myths
• Biohacking and the future of healthcare

Key takeaways:

• Health declines silently — symptoms come late
• Longevity medicine asks: where are you heading biologically?
• The basics still dominate outcomes — most people underestimate them
• The next level is personalization, not more hacks
• Two “healthy” people can have completely different risks
• Mitochondria adapt first — then they start driving dysfunction
• Most mitochondrial interventions are misunderstood
• Genetics gives probabilities, not certainty
• Real optimization = prioritization + sequencing

About Natalia:

Natalia Trpchevska is a medical doctor and holds a PhD in genetics from the Karolinska Institutet.

She is the Medical & Scientific Director at AYUN in Zurich, where she focuses on applying systems biology and layered diagnostics to detect early shifts in physiology — before disease develops.

Her work bridges clinical medicine and research, with a strong emphasis on translating complex biology into actionable interventions.

Timestamps:

00:00 – Introduction & Natalia’s background (Karolinska, genetics → clinic)
03:30 – Why genetics naturally leads into longevity medicine
05:00 – What longevity medicine actually does differently
07:30 – “Physiology before pathology” explained
09:30 – The basics vs. the real next level
11:30 – Same lifestyle, completely different risk profiles
13:30 – APOE4, Lp(a) and personalized strategy
15:00 – Mitochondria: what actually happens as you age
18:30 – When mitochondrial dysfunction becomes clinically relevant
21:00 – Cause vs. consequence: where mitochondria fit in aging
23:30 – How mitochondrial function is actually measured
26:30 – Why isolated tests don’t work (layered diagnostics)
29:00 – What happens after testing: prioritization & sequencing
32:00 – Why “doing everything” doesn’t work
35:00 – IHHT explained: mechanism, benefits, limitations
38:30 – Risks, contraindications & when it backfires
41:00 – Environment vs. lifestyle: what really drives dysfunction
44:00 – The hierarchy: metabolism → inflammation → toxins
47:00 – Why most people focus on the wrong layer
49:30 – What genetics got wrong over the last decade
53:00 – Polygenic risk, probabilities & real-world use
56:00 – Gene–environment interaction: what actually matters
58:30 – Final thoughts: what people still misunderstand about health

Links:

Natalia:
https://www.linkedin.com/in/natalia-trpchevska/
https://www.ayun.ch/

More about Return on Health:
https://returnonhealth.de/

Niko:
https://www.linkedin.com/in/niko-hems/
https://www.instagram.com/niko_hems
https://nikohems.de/

Miguel:
https://www.linkedin.com/in/miguel-medina-stanivukovic-857b9720b/
https://www.instagram.com/miguelmedinastanivukovic/

Rethinking Primary Care and Longevity: Insights with Dr. Takhar. In this episode, Dr. Takhar, UCLA and Harvard trained physician-scientist shares his journey from emergency and internal medicine to building a groundbreaking primary care model focused on human connection, longer physician-patient times, and personalized longevity strategies. We explore how systemic issues hinder patient-centered care and what reforms could make healthcare more effective, preventative, and humane.

Key topics:

• The limitations of conventional healthcare: burnout, bureaucracy, short visits
• The unique model of Primary MD: small panels, extensive diagnostics, longer consultations
• Human connection as a pillar of effective medicine
• The importance of listening and communication skills in healthcare
• Ethical considerations of concierge medicine and access equity
• The role of diagnostics: lipid panels, advanced markers, and their clinical relevance
• Risks, hype, and evidence in emerging longevity interventions
• Future pathways for systemic reform: data, evidence, insurance, and policy shifts
• Lessons from infectious disease training applied to longevity and longevity safety
• The "Mixed Medical Arts" approach: integrating diverse fields for optimal patient outcomes

Timestamps:

• (00:00) - Introduction to Dr. Takhar and the care collision in modern medicine
• (02:07) - Clinical experiences shaping innovative primary care
• (07:12) - The human component in healthcare and systemic barriers
• (10:53) - What primary MD does differently to foster patient trust
• (13:20) - Teaching patients the 'why' behind health decisions
• (14:17) - The vital role of health coaches in adherence and engagement
• (15:32) - The holistic approach combining diagnostics, trust, and relationship
• (18:07) - Addressing ethics and access in concierge-like models
• (19:36) - How to demonstrate value and scalable models
• (22:37) - Overcoming telehealth technical issues in podcast interviews
• (23:58) - The importance of comprehensive, integrated care strategies
• (26:32) - Membership-based care: structure and patient experience
• (27:33) - Ethical considerations of luxury care and future access
• (36:36) - System change: from volume to value and prevention
• (42:48) - Infectious disease background shaping longevity skepticism
• (46:55) - The dangers of hype and unproven interventions
• (50:32) - Bottom-up demand and the future of preventative medicine

More about Return on Health:

https://returnonhealth.de/

Dr. Sukhjit “Sarge” Takhar:

https://www.linkedin.com/in/sukhjit-takhar-md/
https://www.primary-md.com/

Niko:

https://www.linkedin.com/in/niko-hems/
https://www.instagram.com/niko_hems
https://nikohems.de/

Miguel:

https://www.linkedin.com/in/miguel-medina-stanivukovic-857b9720b/
https://www.instagram.com/miguelmedinastanivukovic/?hl=en

This episode underscores the critical need for systems that prioritize genuine human connection, personalized diagnostics, and thoughtful health promotion to advance longevity and overall well-being.